Discussions regarding Experimental drugs and treatments such as AA4500 and Pirfenidone to treat Peyronie's Disease. By expeirmental we mean still in some level of the FDA approval process. This is also the area to discuss other new techniques such as surgiacal or organ regenerating.
Posted: Wed Jul 06, 2005 3:43 pm
Hawkman
The information on these trials seems very confusing. Bio specifics indicate they began a Peyronies Disease trial in 2004. I can only assume it was not phase 3 trials since they are supposedly recruiting for those now. One would think at the phase 3 trial level, fairly large numbers of patients and a variety of Urology Centers would be involved.
Since this is an direct injectable anti-collagen drug I suspect that I am out of luck. If I was not a candidate for VI because of plaque location then I would suppose I would not be a candidate for AA4500 injections.
Usually when there are phase 3 trials, it is not to difficult to find information about recruitment on the web. Has anyone found evidence of actual recruitment, not just a report that there will be phase 3 trials?
Posted: Thu Aug 04, 2005 11:13 pm
j
See the link I posted in the "news" topic. Auxilium announced an agreement with another company that will supposedly manufacture enough AA4500 for Phase III trials.
Don't anyone hold their breath. These things grind on for years, announcements are cheap, and are often made simply to attract new investment or placate shareholders.
j Posted: Sun Jul 03, 2005 4:33 pm
Auxilium is the company that licensed Collagenase from BSTC after BSTC essentially admitted they'd never complete the FDA trials due to lack of money. Auxilium calls it AA4500 and claims to be seeking FDA approval for use against Peyronie's. And Auxilium just brought in $40 million in new investment. Some if it may well go towareds completing the trials for AA4500.
http://phx.corporate-ir.net/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=724870&highlight=
I believe that as of today, AA4500 is our best hope.
dcaptain Posted: Fri Jul 22, 2005 12:52 am
I did a new lit search today on the Pub Med site, and found this, which was published in the June 2005 issue of the Journal of Hypothermia (any subscribers?? Just kidding.) Here's the abstract:
Role of hyperthermia in the treatment of Peyronie's disease: A preliminary study.
Perugia G, Liberti M, Vicini P, Colistro F, Gentile V.
Department of Urology, University of Rome 'La Sapienza', Rome, Italy.
Objective: Previous experience in the treatment of plaque with hyperthermia in orthopaedics led the authors to investigate the effectiveness of this approach in patients with Peyronie's disease.Patients and methods: The study population comprised 60 patients (aged 36-76 years) with advanced Peyronie's disease. Patients were divided into two groups (A and B), with 30 in each. Group A patients underwent local hyperthermia treatment, with 30-min treatment sessions twice a week for 5 weeks. Patients received a total of 10 applications, which reached a local temperature of 39-40 degrees C. A second cycle was repeated after a 1-month interval for a total of 20 treatment sessions. Group B patients were treated with intra-plaque infiltrations using 10?mg verapamil; they received one infiltration once a week for 3 months. Differences between the two groups, as well as between variables (before and after treatment), were analysed using Student t-test and Fisher test.Results: Hyperthermia significantly reduced plaque size and penile curvature and led to an increase in mean scores of erectile function (EF) domain, while verapamil had no such effects. Haemodynamic parameters were not significantly modified in either group. Hyperthermia caused significantly fewer side effects than verapamil infiltrations and was significantly more effective in preventing disease progression. There were no significant differences between the two groups in terms of pain reduction during erection.Conclusions: Results of this study stress the efficacy of hyperthermia in the treatment of advanced Peyronie's disease.
Hawk, AdministratorPosted: Fri Jul 22, 2005 9:17 am
Very interesting Dcaptain. That converts to 102-104 degrees F. I wonder when they say "advanced peyronies disease " if the mean chronic / stable? I suspect not, since they discus pain, progression, etc.
Also was there a date on the study?
I think "Haemodynamic parameters" refer to peripheral blood flow but I am kind of vague on exactly what this means in light of increased erections.
Maybe you could throw the link on your post.
Some of these sites furninsh a more indepth report for a fee.
Joshua, Global Moderator Posted: Fri Jul 22, 2005 10:38 am
DCaptain:
I sent you a personal message about this article. I want to thank you for posting it. I find it fascinating. I would like to try and read the entire research report. I plan on looking for it. I would be happy to pay for the report if there is a fee. I will share it with the forum ; )
I find it interesting that this occurs at only 104 degrees. This may be simple minded but can we now conclude that heat applications could at least be beneficial?
I recall recent posts on BTC where a guy swore hot saunas baths were helping him. I have always believed hot baths helped me. I know this does not compare to the heat they are talking. However, it may show that heat applications are somewhat beneficial. I can't now see where heating pads, hot baths, warm thera patches etc... might not be a nice addition to our home based therapies.
j Posted: Fri Jul 22, 2005 1:44 pm
Very interesting; as always, I'd like to see the actual numbers.
This could save me some serious money. The A/C just went out in my car. Maybe I'll just not fix it, and drive around with the windows rolled up
Hawk, AdministratorPosted: Fri Jul 22, 2005 2:57 pm
A couple of things j. I think subjecting your entire body to heat would be a systemic solution to a localized problem. It could backfire and throw your entire body into a curve. ;)
My final thought is that regardless of the science or method behind this study one thing is clear. We can be sure that on this one, they aren't being motivated by profit, that is, unless they sell donut shaped heat packs.
I have expiermented with both heat and cold. I kind of concluded "hmmmm, inflamation should respond to cold". I was so lacking in evidence I gave up.
Now I wonder, do you think the neighbors will complain if I sun my penis in the open window and call it medical therapy?
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j Posted: Fri Jul 22, 2005 5:25 pm
Depending on local ordinances, you might need to apply for a permit first. And be sure to use SPF 30 sunblock.
But seriously, wouldn't it be great if something like this worked? Obviously I have my doubts. But it's cheap, easy, noninvasive. Physical Therapists could start doing it tomorrow, it wouln't require any new FDA approval.
hawk, Administrator Posted: Fri Jul 22, 2005 5:35 pm Quotej:
But seriously, wouldn't it be great if something like this worked? Obviously I have my doubts. But it's cheap, easy, noninvasive. Physical Therapists could start doing it tomorrow, it wouldn't require any new FDA approval.
It would be great and this information is enough to at least make me feel i would not be aggravating the situation. I have a handheld shower unit that I will end every show by directing over the area for several minutes. A few small hot packs should finish the job. I rate it right up there with Acetyl L-Carnitine. It has some evidence that it helps, little or no down side, and It is a hell of a lot more than my well known Urologist is offering me.
dcaptain Posted: Fri Jul 22, 2005 9:12 pm
Now I see the button for "popcorn" and "bacon," but where's "penis" on this microwave?
Sorry for the delay guys, sometimes posting at work isn't so easy. Here are the links to both the PubMed abstract:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16019862&query_hl=1
and the journal itself:
http://taylorandfrancis.metapress.com/app/home/contribution.asp?wasp=cb6064e00794422d861a386753223f16&referrer=parent&backto=searcharticlesresults,3,869;
That PubMed site is great if you haven't seen it. You can pull down a lot of great abstracts.
I agree - I think a little heat can't hurt, right? Hell, I'm swallowing supplements and I have no idea what they might do to me. What's a little heating pad gonna do?
dcaptain
zenvault GUEST Posted: Fri Jul 22, 2005 9:15 pm
International Journal of Hyperthermia can be found at www.ingenta.com/content
The abstract shows 1 other affiliation to the study. It is the hyperthermia unit of Regina Elena Hospital, Rome,Italy.
In addition to the article "Role of hyperthermia in the treatment of peyronie's disease:A preliminary study" there is another in the same June 2005 issue called "use of local hyperthermia as prophylaxis of fibrosis and modification in penile length following radical retropublic prostatectomy" The second study evaluation was made on the effectiveness of local hyperthermia in reducing possible penile shortening following prostatectomy.
Hawk, Administrator Posted: Fri Jul 22, 2005 9:27 pm Quotezenvault:
International Journal of Hyperthermia can be found at www.ingenta.com/content
The abstract shows 1 other affiliation to the study. It is the hyperthermia unit of Regina Elena Hospital, Rome,Italy.
In addition to the article "Role of hyperthermia in the treatment of peyronie's disease:A preliminary study" there is another in the same June 2005 issue called "use of local hyperthermia as prophylaxis of fibrosis and modification in penile length following radical retropublic prostatectomy" The second study evaluation was made on the effectiveness of local hyperthermia in reducing possible penile shortening following prostatectomy.
I would call this some very interesting information and I thank you for the valuable post Zenvault. The link seems to lock up on the main site. I am very interested as are others. Could you fix the link. If you need to email you can do so at admin@PeyroniesSociety.org
Thanks
j Posted: Thu Aug 04, 2005 7:11 pm
http://biz.yahoo.com/prnews/050802/nytu105.html?.v=18
I just can't believe how long this has been dragging on! The market for this drug must be absolutely huge considering the incidence of peyronies.
One would think that there would be a rush to get this out the door.
Found a new abstract today guys. I'm not saying "good," "bad," or "indifferent," but am passing it along to add to the discussion. They list "the best results ever," but I'm not sure if or how this relates to mean results for the group (or maybe it is the mean?) I'm not sure. Anyways, just passing along.
Hope all is well with everyone.
dcaptain
**********************
Int J Radiat Oncol Biol Phys. 2005 Sep 15; [Epub ahead of print]
Results of radiotherapy for Peyronie's disease.
Niewald M, Wenzlawowicz KV, Fleckenstein J, Wisser L, Derouet H, Rube C.
Clinic for Radiooncology.
PURPOSE: To retrospectively review the results of radiotherapy for Peyronie's disease. PATIENTS AND METHODS: In the time interval 1983-2000, 154 patients in our clinic were irradiated for Peyronie's disease. Of those, 101 had at least one complete follow-up data set and are the subject of this study. In the majority of patients, penis deviation was between 30 and 50 degrees , there were one or two indurated foci with a diameter between 5 and 15 mm. Pain was recorded in 48/92 patients. Seventy-two of the 101 patients received radiotherapy with a total dose of 30 Gy, and 25 received 36 Gy in daily fractions of 2.0 Gy. The remaining patients received the following dosage: 34 Gy (1 patient), 38-40 Gy (3 patients). Mean duration of follow-up was 5 years. RESULTS: The best results ever at any time during follow-up were an improvement of deviation in 47%, reduction of number of foci in 32%, reduction of size of foci in 49%, and less induration in 52%. Approximately 50% reported pain relief after radiotherapy. There were 28 patients with mild acute dermatitis and only 4 patients with mild urethritis. There were no long-term side effects. CONCLUSION: Our results compare well with those of other studies in the literature. In our patient cohort, radiotherapy was an effective therapy option with only very rare and mild side effects.
Found another new abstract - this time surgical. Am posting here under "News" but I guess it could go under "Surgery" as well. Just adding to the body of knowledge - seems these guys may have a modified procedure (?).
Hope all is well guys.
dcaptain
*****************************
'Straightening-Reinforcing' Technique for Congenital Curvature and Peyronie's Disease.
Mantovani F, Patelli E, Castelnuovo C, Nicola M.
Department of Urology, IRCCS Ospedale Maggiore, Milan, Italy.
Objectives: We report an initial randomised study on surgical techniques with subsequent intensive application of our procedure. Materials and Methods: We modified Ebbehoj-Metz technique by a 'straightening-reinforcing' (S-R) double stitch: the first performs the plication, the second tightens it, thus preventing tension during erection. This is different to the simple Ebbehoj-Metz stitch that only provides plication but, as it does not provide reinforcement, does not prevent recurrence. From 1995 to 2000 78 plications were performed: 60 for congenital curvatures (age range 18-32 years) and 18 for Peyronie's disease (Peyronies Disease; age range 36-58 years). During the first 3 years, i.e. between 1995 and 1998, patients were randomised to S-R plication (20 congenital and 5 Peyronies Disease) and Nesbit procedure (20 congenital and 5 Peyronies Disease), for a total number of 50 patients (40 congenital and 10 Peyronies Disease). The last 28 patients, operated between 1998 and 2000, were assigned exclusively to S-R plication. We delayed study publication in favour of an adequate follow-up. Results: No patient reported a decrease in erectile function and all reported easy vaginal penetration within 3 months. In 60% of the patients undergoing the Nesbit technique, restoration of a fully satisfactory coital activity was delayed because of pain during erection; 35% of all patients had some problems with the coronal suture which disappeared 1 month after the operation, and 15% reported decreased sensibility of the glans. Recurrence rate was not significant for all patients of all groups, even if 3 Peyronies Disease patients of the S-R plication group and 1 Peyronies Disease patient of the Nesbit group received no benefit from the operation. Conclusion: S-R plication is not better than the Nesbit procedure. However, for low degrees of penile bending, both congenital and acquired, we do not think it strictly necessary to perform the more invasive Nesbit operation (requiring opening of Buck's fascia, detachment of the neurovascular dorsal bundle or urethra and albuginea excision). Modified plication may be a minimally invasive and effective treatment suitable for most curvatures treated in day clinics and under local anaesthesia.
As many of you know, Peyronie's and Dupuytren's Contracture are generally considered to be 2 aspects of the same underlying disease. Now a research group claims they've found the location of the underlying chromosomal abnormality.
I found this on http://centerforgenomicsciences.org/research/, which is a web site describing research projects at the Center for Genomic Sciences, part of the Allegheny-Singer Research Institute, ASRI, the research arm of Allegheny General Hospital:
"Dupuytren contracture is a disease of the fascia in the hand that does not usually onset until the fifth or sixth decade of life and is most prevalent among the Xanthocroix peoples of Northern Europe. This project was begun in 1995 in collaboration with our Swedish colleague, Dr. Ake Nystrom. Dr. Nystrom, currently at the University of Nebraska in Omaha, Dr. Ehrlich and Dr. Hu have completed several specimen collection trips to Sweden to access informative Scandinavian families that Dr. Hu and Dr. Preston successfully used to identify a locus on chromosome 16. "
J
Just a short note.
I have heard that Scandiavian are prone to this. Most folks that I know are of Swedish and Norse decent like myself and have it. Seems that sometimes it goes hand in hand with Peyronies Disease. Oh well.... Another bump in the raod.
Some details:
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1399-0004.2005.00504.x
Is it just me, or does this seem like a fairly big deal? Maybe not?
I think it's been known for quite a while that Dupuytren's is hereditary, and that Dupuytren's, Peyronie's and Ledderhose are essenitally the same condition.
Like a lot of medical 'breakthroughs' the first result will probably be a test that will tell you, while you're still young, that you're going to get Peyronie's Disease later in life and there's nothing you can do about it. Great.
Eventually, some researcher will find the specific bad gene, and then unravel exactly what that gene does, and - some day - hit on a way to compensate for the defect. We might all be dust by then, but future generations won't have to endure this curse.
J,
A fellow Swede thanks your for this very interesting information.
dcaptain, actually this is a big deal, sort of. While there is apparently no significant research being done on Peyronie's, that's not the case with Dupuytren's. That research paper starts out with this statement:
"Dupuytren's contracture (DC) (OMIM 126900) is the most common connective tissue disease of mankind..."
I've seen other research on Dupuytren's too. Tissue changes, cell biology, the biochemistry of fibrosis. Genetics people have been interested in Dupuytren's for years because it's fairly easy to study - there's a nice geographic/ethnic trail to follow. Hand surgeons all over the country deal with it every day. Insurance companies pay big bucks.
Basically few researchers would want to work on Peyronies Disease because it's so darn difficult. Hard to find patients. Guys don't like to talk about it. Hard to get objective measurements. Hard to take tissue samples. But with Dupuytren's, announce a study and patients will beat a path to your door, happily show you their messed-up hands and let you jab and poke them.
When they figure out Dupuytren's, we'll have the answer to Peyronie's too.
As I wrote on another thread. the connection with DC may be our only hope for getting collegease drugs (like AA4500) investigated and approved.
On a different, very speculative note: Scandinavian countries have long had the reputation for having a high standard of living, including relaxed sexual mores, while at the same time they mysteriously have higher suicide rates than the rest of the world. I wonder if the larger numbers of cases of Peyronies Disease in that region could account for enough additional suicides (with Peyronies Disease-related depression going underreported, understandably) that the total would therefore exceed that of other countries. After all, suicide numbers are not massive in the first place. If statistics can show that a disproportionate number of Scandinavians who took their own lives for reasons unknown were 45-60 years old, I would really suspect this is the mystery factor.
A grim thought, kevin.
I've seen some numbers for the prevalence of Dupuytren's in Scandinavia and in particular, a study in Iceland showed a high number:
http://www.emedicine.com/derm/topic774.htm
I haven't seen numbers for Peyronie's in Scandinavia It's clear that there's a strong linkage between the problems - according to Dr. Mulhall's web site, 15% of men with Peyronies Disease are found to have Dupuytren's as well. Note that Dupuytren's might appear later in life - after the Peyronie's - so the number could well be higher.
I read this on a Dr. Whitehead's Site:
I am now performing the "Single Relaxing Incision for Correction of Penile Curvature based on Geometrical Principles (Egydio Procedure)" after having been trained by Dr. Paulo H. Egydio in Sao Paulo, Brazil. Does anybody know if this is a different surgical intervention than Cross stitching the backside ( ie does it result in a two inch reduction of length for which massive psychological counseling would presumably be needed together with a pocket full of anti-depressants
Once in a while you actually find something useful in the middle of all the stupid graffitti ((junk posting) on the old BTC forum:
From a Yahoo business news item:
"In August 2005, Auxilium signed an agreement with Cobra Biologics Ltd.
for the further development of the manufacturing process, scale up and
manufacture of clinical supplies for AA4500 for both Peyronie's and
Dupuytren's Diseases."
and
"Research & development costs for the quarter ended September 30, 2005 were $4.5 million compared with $4.9 million in the comparable year-ago period. The decline reflects lower in-licensing fees, partially offset by an increase in spending on various product candidates, particularly manufacturing scale up for AA4500, ongoing investment in developing the licensed transmucosal film technology and Testim phase IV clinical studies in hypogonadal men with type II diabetes."
Now to find out the where and when about those trials...
Full article at:
http://biz.yahoo.com/prnews/051108/nytu080.html?.v=27
See this forum's "News" thread for latest developments, excerpted from this November article:
http://biz.yahoo.com/prnews/051108/nytu080.html?.v=27
One of the most comprehensive reports on all aspects of Peyronies Disease is an article written by Dr. Eli Lizza at the URL shown below. The article covers in depth almost all of the topics on this forum. There is good information on iontophoresis (EMDA) which is a current topic on the forum.
It may have been posted here before as I have not gone back and checked all the topics, but in any case it's a good report.
Larry
http://www.emedicine.com/med/topic3422.htm
Thanks for the link, Larry. It's an interesting summary.
Unfortunately it seems to answer all the questions except 1: do any of those therapies work? I always end up at the same place with that one. For each treatment there's a small poor-quality study that appears to say "yes, maybe". And a bunch of posters on forums like this saying - I tried it and it did nothing. Years go by and the question is never resolved - the list of therapies continues to grow but nothing is ever really settled. We just get more urologists prescribing more things, more money being spent, and seemingly little if any improvement for patients.
So that's my message of cheer for the new year.
I would have to agree that neither this nor the preceding couple of years have been cause for party hats and noise makers unless you are a marketeer peddling the old potions, we have at the very lest been able to show that there are a significant number of us who are affected and willing to share our journeys. some interest in collagenase, refined surgical techniques, more demanding and informed patients. . . these are all pretty good things. Happy New Year and many more to follow. Bentley
Something positive to start the new year off right.
Dr. Anil Kapoor MD FRCS(C) has been treating Peyronies Disease with ESWT since July 2003.
He will be interviewed on the 'Talking Sex with Sue' program on Sunday January 15th, 2006 at 11pm EST (10 CST) with repeats at 2am, and the following Thursday, on the Oxygen channel.
The interview will provide general Peyronies Disease information to listeners and raise awareness of Peyronies Disease within the general public.
If you get the Oxygen channel, we hope you will tune in. Please forward this notice to physicians, or others who may benefit from the information.
Sincerely
Robert Mitchell
PainFree ESWT
www.painfree-eswt.com
1 866 444 3798
peyronies-info@painfree-eswt.com
Thanks to J for the following. Most of it is his, with a bit of a rework for posting on our website.
Here is, apparently, a recent PowerPoint presentation from Auxilium makers of AA4500 (collagenase), that answers some questions, sort of. This drug is going through FDA trials as a means of remolding scar tissue in at least a few different conditions including Peyronies Disease.
http://www.secinfo.com/d14D5a.v27Ry.d.htm
The AA4500 slides are pretty deep down the page. Note the proposed timeline showing AA4500 being marketed in 2008-9. As J notes, Often investor presentations are overly optimistic. Other interesting points: they claim verapamil is "ineffective" ,that surgery is the only "approved" treatment for Dupuytren's (not true) - and, that AA4500 has worked on Peyronie's. Their initial level II trials used 9 injections and they hope to reduce that number in their IIb trials.
Pirfenidone is an investigational anti-fibrotic drug that was in clinical trials not long ago for use against pulmonary fibrosis. At least one participant in those trials happened to also have Dupuytren's Contracture (a condition with links to Peyronies Disease) and he reported to a newsgroup that it resolved his DC. Pirfenidone appeared promising and it was discussed on the BTC board last year (by Joshua, among others) but nobody has even mentioned it since then. I was especially interested in hearing from the person who posted that he was in an upcoming trial of the drug for a fibrotic disorder and is also a Peyronies Disease sufferer, or so he says (we all know how the BTC board is). The old thread is this one:
http://www.biospecifics.com/forum/readThread.asp?forumID=14&threadID=3434
Some studies are discussed in the following two links:
http://www.clinicaltrials.gov/ct/show/NCT00063583
http://www.keepmedia.com/pubs/PRNewswire/2005/03/29/790464
http://www.intermune.com/wt/itmn/pirfenidone
(Copied from "New Topics" thread)
couldbeworse wrote:
"It looks like SUNY Stony Brook is doing some work with collagenase: http://www.clinicaltrials.gov/ct/search?term=collagenase&submit=Search
They're teaming with Biospecifics in trials for Duypuytren's and Frozen Shoulder. Why not Peyronies Disease? If no one on this forum tells me why not, then I'll ask the PI at Stony Brook, Why not?..."
If the researchers at Stony Brook are testing a treatment fo DC, they are clearly not in the Urology department and may not even know of the connection with Peyronies Disease. Even if they are made aware of it, I doubt they will even consider injecting collegenase where it needs to be injected for Peyronies Disease purposes. I guess the best thing to do is make sure they do know (with links to the sources of that info) and ask they they confer with their colleagues in Urology. In fact, if the study is large enough, there is likely to be at least a couple of test subjects who actually have both DC and Peyronies Disease. So maybe the researchers can be convinced to include Peyronies Disease among the many other conditions they ask about in their recruiting questionairre. That way, any incidental effect of the drug on Peyronies Disease could be noted at the end of the trials and, if it's beneficial, flagged for further study. Enter the Urologists.....
Again, thanks to Mark's support for this link. My first, 1 second impression was that it would be a bunch of the usual hype, but this is a very interesting article. I suggest you read the entire articles. They are short. This actually worked in rabbit penises even after removing all corpra cavernosa tissue. Clearly there is a long way to go but they have come a log way. If I was in my 20"s or 30's and had Peyronies Disease, I would be fairly confident that major help is on the way from this and other research.
"In the study, adult male rabbits with severely damaged penises received a graft of specially engineered penile tissue. The animals then re-grew full penises that functioned normally...
Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University in Winston-Salem, N.C. His team reported its findings Tuesday at the American Urological Association annual meeting, in Atlanta."
Here are two links incase one goes inactive.:
http://www.healthday.com/view.cfm?id=532858
http://news.yahoo.com/s/hsn/20060523/hl_hsn/scientistscreateartificialpenis
Mark,
Way to catch those articles, very interesting, plants seeds of hope in myself. Hawk you never know man, in another 5 years they could have that science perfected. I think its important to keep hope with this disease, just not unrealistic hope. Perhaps someday it will be as easy as the doctor injecting the tissue into my penis, which can than regenerate into new tissue and grow.
What about the collagenese injections with Auxillium? I think for the average person and myself we hear FDA trials level 1,2, and 3, and that Auxillium is in phase 2, but what does this mean, how long is phase 2, how long is phase 3? What happens after that, you can try the injections? Will the FDA publish the results of their studies so all of us sufferes can see the success of collagenese injections?
PDLabs claims their in phase 2 of FDA trials, someone said that when they called them like 4 years ago they claimed they were in FDA trials, do the trials take this long? What is the average time frame to go through all the phases? I think a lot of people don't understand these time frames, if anyone could give a detailed response on what each phase is and how long the whole process takes it would be good for everyone to understand, anyone want to give us a minor in FDA trials?
ComeBackid
Effect of intralesional interferon-alpha 2b combined with oral vitamin E for treatment of early stage Peyronie's disease: A randomized and prospective study
Tansel Inal, Zafer Tokatli, Murat Akand, , Erol Özdiler and Önder Yaman
Department of Urology, University of Ankara School of Medicine, Ankara, Turkey
Received 26 April 2005; accepted 2 November 2005. Available online 11 April 2006.
Abstract
Objectives
To compare the efficacy and safety of intralesional interferon-alpha 2b combined with oral vitamin E or intralesional interferon-alpha 2b alone or oral vitamin E alone for the treatment of Peyronie's disease.
Methods
From January 2000 to March 2002, a total of 30 consecutive men with Peyronie's disease were randomized prospectively into three different treatment groups. All the patients were assessed objectively with penile duplex Doppler ultrasonography for plaque size, location, and presence of calcification before and after treatment. Subjective data were obtained by querying about the improvement in penile pain and by using the "global efficacy question" for the assessment of the quality of sexual intercourse at the end of the study. A total of 5.0 × 106 U of interferon-alpha 2b was given once per week directly into the plaque for a period of 12 weeks. Patients received 400 IU of vitamin E orally twice daily for 6 months.
Results
At the 6-month follow-up visit, we did not find any statistically significant changes in the objective parameters when compared with the initial findings in each group or among the three groups (P >0.05). We did not observe any clinically significant improvement in the subjective parameters among the three groups (P >0.05). However, all patients who were treated with interferon-alpha 2b experienced brief flu-like side effects.
Conclusions
Our findings indicate that 5 million units of intralesional interferon-alpha 2b injection therapy either alone or in combination with vitamin E does not appear to be clinically effective in the management of early stage Peyronie's disease compared with only oral vitamin E.
[quote ]
interferon-alpha 2b injection therapy either alone or in combination with vitamin E does not appear to be clinically effective in the management of early stage Peyronie's disease compared with only oral vitamin E.
[/quote]
And we all know how well vitamin works. One of the studies in liams posted link (under "Resource Liabrary") indicated no difference in Peyronies Disease with or without vitamin E.
Someone on the Yahoo group for Peyronie's & Chordee just turned up the patent record for a Peyronies Disease treatemnt using collagenase. The patent dates from 1982 and was issued to Dr. Gelbard, whom we all recognize is now one of the best-known urological surgeons in the country. The link given in that post (and included below in mine) is an official and detailed description of the patent. However the posting went on to claim that the treatment was found ineffective, that the patent has expired, and, curiously, that the material from the experiments is still being sold today!
This is all very confusing because we know collagenase is again being studied today as a possibly very effective treatment for Peyronies Disease. Auxilium Corpoation is the current holder of a (different?) patent for an investigational collegenase drug they call AA4500. If they are not one and the same, then the two patents must be different is some substantial way, but how? (The 1982 patent seems to cover every variation of the substance and every imaginable way of administering it for Peyronie's.) In any event, if we can verify that collagenase indeed was found ineffective decades ago, it would mean that our hopes for AA4500 are dashed - or am I missing something?
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4,338,300.PN.&OS=PN/4,338,300&RS=PN/4,338,300
Kevin,
I to have heard that same rumor and I can't remember where exactly- being that collaganese already did not work when tried. This to made me wonder am I getting my hopes up for something that will turn out to be ineffective?
However, just recently I was talking to someone who was at the AUA and met the head doctor doing the collaganese injection trials that are under way right now apparently. From what he tells me things are going well, he seemed to hint to the person I talkedto that they are seeing positive results, however the person I talked to said the doctor told him Auxillium is being very cautious and purposely not overhyping their product. This gave me some positive hope and I wanted to pass it along after I read your post.
Your questions are very good and common sense makes me ask why Auxillium thinks collaganese would work now?
This is something that we should definately look into, maybe Tim or any other doctors or physicians can inform us on this subject.
ComeBackid
Collagenase itself is an enzyme produced naturally by your body. It dissolves collagen, which is a principal component of Peyronie's fibrotic plaque.
Verapamil (and possibly interferon) stimulates the body's own production of collagenase. Unfortunately it seems not to work very well, at least so far.
I know there are several forms of collagen, and there may be different forms of collagenase too. I believe the BSTC patent is for an 'injectable form' of collagenase which is supposed to be more effective than whatever was tried back in the 80s.
Previous studies have already shown conclusively that it can work for Dupuytren's contracture, by dissolving enough of the band to allow it to be snapped. It's use for Peyronie's might be more problematic, but that's what Auxilium is trying to work out.
According to Gelbard's early-80's patent, the administration WAS to be "directly into the plaques which form in the course of the disease" and is described as "interlesional". We can only assume that any subsequent patent-based experiments must have been conducted accordingly. Though I haven't read anything that verifies the reported findings that the drug was found ineffective, it does seem likely since we all would have heard about anything at all positive.
Still, I'm hoping that the new experimentation is based on some significant variation in either the substance or delivery, and is therefore not just going down an old forgotten road that leads to a dead end. If anyone knows for sure what is different between then and now, please let us all know. In fact, with collagenase trials supposedly underway now (and previous ones completed), why is it that no one on this forum has reported being a participant? Is our forum (or the study) so small that it's statistically unlikely that we have a participant among our members? Or perhaps I just overlooked a post from someone about that...
I don't think the trials are underway. My Uro is Dr. Levine and I asked about the collagenase treatment last Friday. He said he is working together with some other Doc's to develop the protocols for the trial. He thinks it may get underway later this year. He is encouraged and thinks this may be a viable treatment. I think if trials were underway, he would know about it...
Wantitstr8,
I was told they are underway and that some people in the study are receiving placebo injections. Those people who receive those, are then told at the end of the study and will be allowed to get the real injections for free for taking the time to participate in the study. This is what was passed on to me by a reliable source who was at the AUA and said they spoke with the doctor doing the studies. I'll press for more information and see if I can't find out some more facts about the trials. The company is located here in Pennsylvania, but I've never heard of the town, I wonder if they are doing the trials here?
ComeBackid
i dont believe that is true. I talked to the company myself. The trials have not started yet. There is still a lack of study drug and it does not sound like the protocol is even finalized yet. I think Auxilium is dissappointed about this. The coordinator for the study does not even work in PA but in a home office in NJ. The good news is that Auxilium appears very committed to bringing the product to market and something I have been thinking of recently if they get a frozen should indication first then certainly urologists could start using it off label if inital results are promising.
Kenm,
You could be quite right, I will check back with my source and question them in more detail on this. Perhaps they are confused or simply wrong. I guess if we wanted to check we could call the company ourselves and it sounds like you did that, good work!
ComeBackid
so when is this new injection going to be out? Dont the trails take like 4 years? They got to find a cure, they got to.
Howcanthisbe,
When wil they be out? Thats the million dollar question, I don't think anyone knows for sure, just estimates, people have been saying next year sometime, maybe like springtime. The thing I don't understand is why do they need to go through FDA trials, PDLabs was selling their product TV without going through FDA trials and still hasn't, probably mainly cause then the documented efficacy will be shown to be 0(since there are not other studies than the one done by Dr. Fitch).
However, J has stated that if the injections see good results for other things such as dupuytren's contracture (http://en.wikipedia.org/wiki/Dupuytren%27s_contracture), or frozen shoulder (http://en.wikipedia.org/wiki/Frozen_shoulder), they may move ahead and do off label use on peyronies patients.
Does anyone know when they will start the trials or is there a way for us to find out? ???
One guy stated he talked to the company but I don't know how much they will tell you over the phone.
ComeBackid
I think their website will give the most optomistic projections. Here is a blip and a link to more info.
http://www.peyroniessociety.org/news.htm
"Their initial level II trials used 9 injections and they hope to reduce that number in their IIb trials."
So it seems that they have done some studies already, then my source could be right in that he talked to the doctor running this. Perhaps the new protocal is just another study or the study with "less" injections.
ComeBackid
My understanding is that once a drug like verapamil is FDA-approved for certain uses, it can also be prescribed for certain other conditions and this is called "off-label". That's how PDL can sell verapamil for Peyronie's, and urologists can inject it. Whether this might apply to injectable collagenase, I don't know. But clearly it would require some urololgist to be willing to push the envelope a bit.
I think one drawback of this is that insurance companies may not cover off-label prescriptions.
There are probably some big gaps in my understanding here. We need someone with more understanding of the drug business to really explain this.
J,
Now that you mentioned it your right, and I remember reading this on the literature PDL labs sent me. Actually most of the drugs used in psychiatry are off-label drugs and covered by insurance companies. However with something like this I'm sure most places would try and deny coverage, I know for me MEDCO has done everything they can do to deny me coveage, changing their ridiculous excuses, and I've continued to fight them and finally got coverage.
Heres some information on off-label use.
Off-label (http://en.wikipedia.org/wiki/Off_label)
ComeBackid
hey wantitstr8,
i'm sure everyone would be interested in learning more about this "end of the year" advancement! thanks for the info.
dcaptain
I asked him about it at my last visit...posted it somewhere...I can't remember where. Anyways, he confirmed that the end of the year treatment is the AA4500 collagenase treatment. He said the treatment showed real promise in the early 80's but the patent was owned by a Company that did not pursue the development. He really thinks the treatment may be viable. He is working with several other Uro's on developing the protocols for the trials...I'll keep everyone informed...
wantitstr8 - I don't understand how a urologist could say that AA4500 could be available at the end of this year. Phase III trials haven't even started, and Auxilium is telling their own investors to expect it in 2009.
J,
I agree with you, but once again if its coming from Dr. Levine there must be some kind of truth behind it. Kind of like with the traction devices, if Dr. Levine didn't have some faith in the things he wouldn't be doing a study with them. My source told me Auxillium is purposely not releasing any info on the product cause they dont' want any speculation. But as for what Dr. Levine says that is very puzzling, I just hope your dead wrong J! ;D
ComeBackid
Maybe he was talking about trials not general availability to the public.
Yes that could be it. IF those trials actually happen, AND the stuff obviously works, AND word gets out, the situation could get interesting. While our condition isn't life-threatening, it has -arguably - no effective non-surgical treatment, so urologists would have patients banging on their doors asking for AA4500. I wonder if there's any way to make a drug like this available, outside of the trials themselves, before formal FDA approval. Previous trials have already established its safety.
One thing I'm still pondering is that it seems like verapamil injections don't work that well. And a lot of people point out that injections will cause more scar tissue or more plaque nodules. So while we all are getting a little excited and hoping the collaganese injections work, what about the fact that they will be delivered through injection method and could make more plaque, or aggravate previous plaques if the drug doesnt work. Also even if it does work on the original plaque one has, what if the injections create more plaque? Although they are trying to reduce the number of injections down to less than half a dozen, so I suppose that could prove to be helpful in not creating anymore plaque.
ComeBackid
As far as the end of the year, I'm not sure what he meant...maybe I get to be one of the guinea pigs. I know he said a viable treatment may be available by the end of this year...when I visited two weeks ago, I asked again and he confirmed it was the AA4500...that's all I really know.
As i stated in an earlier post if the drug becomes available for another indication urologists will be free to use it off label for peyronie so it might be prior to 2009.
Quote from: pudder135 on June 20, 2006, 10:31:33 PM
a lot of people point out that injections will cause more scar tissue or more plaque nodules. So while we all are getting a little excited and hoping the collaganese injections work, what about the fact that they will be delivered through injection method and could make more plaque, or aggravate previous plaques if the drug doesnt work. Also even if it does work on the original plaque one has, what if the injections create more plaque?
ComeBackid,
Assuming AA45oo breaks down collagen scar tissue, it seems a needle delivery system would not be a huge concern. if it can't prevent collagen scar tissue in the needle trail, it sure isn't going to break down or prevent established scar tissue adjacent to the the injection.
Ok assuming it is used off-label for peyronies does that mean most insurance companies won't pay for the injections? What would be a good estimate of a price of a series of 5 injections of collaganese done by a doctor ? I would want to go to a doctor who is well trained in injecting into the penis itself.
ComeBackid
http://www.clinicaltrials.gov/ct/search?term=collegenase&collagenase.ID=term&collagenase.badWord=collegenase&collagenases.ID=term&collagenases.badWord=collegenase&collegiate.ID=term&collegiate.badWord=collegenase&collagens.ID=term&collagens.badWord=collegenase&colleges.ID=term&colleges.badWord=collegenase&I+meant+collagenase.x=6&I+meant+collagenase.y=8
Found this and thought I'd pass it on.
Liam
See the 'investor relations' section on www.auxilium.com. There's an announcement today that I think is mostly good news. As I interpret it, it says they've concluded that AA4500 works well on Dupuytren's and they've decided to spend more money on building up a manufacturing capacity.
Speculating a little further, I think this is good news, and bad. The good news is they're going ahead with Phase III trials for Dupuytren's and Peyronie's, and those involve a lot of patients, so they'll need more AA4500. The bad news might be that they really hadn't comitted to those trials before now, so they don't have the necessary supplies of the drug yet.
The bottom line has to be good news, because they're talking about spending millions on actually producing the drug itself, not just more PR. Spending those millions is going to increase their financial losses for the year.
Well like I said, my source told me they were seeing results in the testing of the drug, so despite the fact that some doctors(including Dr. Levine) are planning a future protocol as we speak, they must have done previous tests to show the drug worked, probably in a small group of patients. I'd say this is only good news, finally they are going to advance foward with this thing. Seems like Dr. Levines prediction of the drug being available by the end of the year may happen.
Now the real question is will my insurance cover the injections and just how expensive will they be.
ComeBackid
Could a doctor just try out a drug on "small numbers" without FDA approved and monitored drug trials? I think that is the point of the FDA and trials, to prevent doctors from experimenting on patients. That why we have such a long approval process because they have to jump through hoops until the FDA is satisfied that the trial format meets their guidelines for patient safety and accurate reporting of data.
Or so i thought
If AA4500 had FDA approval for any use, I believe that would open up the possibility of "off label" use for other conditions at the discretion of a physician. That's how urologists are able to inject verapamil. Insurance coverage might be an issue. But hey, I'll pay.
BSTC got essentially the same results 10 years ago in a trial at SUNY, using collagenase on Dupuytren's contractures. It's not clear to me why Auxilium is making a big deal about this latest demonstration of already established facts. If I were a cynic, I'd say that they're just running another cycle of announcing how "promising" this drug is, pumping the stock price and bringing in new investment. But, I'm not a cynic.
If they're putting money into production, that's good. Whatever else happens, we can't get the treatment if there's no supply of the drug.
The other good thing is that there's now simply no doubt that AA4500 can safely break up this tissue. Dupuytren's is a good condition on which to test this stuff because results are clear and unambiguous. No nonsense about "erection quality", "plaque reduction" or patients being asked to evaluate their own improvement. You inject AA4500 and put force on the contracture, snapping it if possible. Then you straighten the finger as far as it will go and measure the angle. No smoke, no mirrors.
What we don't know is how this drug would be applied to Peyronie's, which is similar tissue but a very different situation mechanically. However, it seems to me that there should be a way to make it work.
J, anybody,
Am I correct in saying that at this point there is no FDA approval for general use of this drug so it could not have been administered to anyone for any reason without a detailed FDA approved clinical trial in place for that specific use?
As far as I know, BSTC's 'injectable collagenase' has no approvals.
Here is a link to Clinical trials and what happens in each phase. On that clinical trials I noticed that some ot he experiments using injectable collaganese are in phase II and even phase III trials, meaning there could have been some smaller studies that showed it was working in the phase II trials previously. I don't think my source would of made this up as they are very credible and repubatle in the Peyronies Disease community.
FDA Trials (http://en.wikipedia.org/wiki/Clinical_trial)
ComeBackid
ComeBackid,
This topic is getting exasperating. Either there were FDA trials for AA4500 on Peyronies Disease, or there were not. If there were, surely someone has the link since it would be a matter of public record and something the company would hype. If there were not FDA clinical trials, then it has never been used on Peyronies Disease, at least ethically and legally.
Not necessarily. The drug could have been first investigated oversees. Secondly in the early 80's when the trials apparently were first performed there was much less oversight. I dont know whether this company is a typical NASDAQ pump and dump or not but the good news is it does have real earnings with its testim product. I agree it appears someone has seen that the drug works. If the drug appears to be working in phase IIB or III clinical trials for peyronies but has not yet gotten aproval for that condition but has gotten approval for some other condition then it certainly could be used off label. Insurance companies would not pay for the treatment however. That probably would be small price to pay for a legitimate cure.
Hawk, 'exasperating' also describes my feelings after 10 years of trying to figure out what BSTC/Auxilum are actually doing with this drug, the efficacy of which has never really been questioned. Our nation's intellectual property laws are often praised as being a big factor in our success, but these laws cut 2 ways. The holder of a patent has no responsibility to actually do anything with it or allow the rest of mankind to benefit from it. The 'invention' of injectable collagenase might have been a stroke of geniius, or just an obvious, incremental improvement to something that already existed, but once someone is able to get a patent on it, the bottom line is - nobody gets well until somebody gets rich.
The extremely lengthy and expensive FDA approval process was intended to prevent another catastrophe like Thalidomide. But today, in many cases, it's just an out-of-control bureaucracy that impedes progress. There's no realistic possibility that injections of small amounts of collagenase would pose any systemic health risks.
Having said all that, let's treat this announcement as basically the best news we've had in quite a while.
Hawk,
Sorry to exasperate you... I'm just trying to sort through the facts, and no one really seems to have a clear cut answer. I believe my source as he had no reason to lie, as I said before I will requestion, still waiting for a reply via email. It exasperates me that I've had this disease for 7 years and they've only recently gotten into high gear in trying to come up with a solution for peyronies. I think we are all expaserated and getting a bit grouchy, and rightly so!
J, I agree with you about the intellectual property laws going both ways. As tim has previously pointed out look what PDLabs did. They took verapamil which already had FDA phase I approval for safety and got a patent on the delivery mechanism itself. As tim has pointed out they've just sat on this patent and haven't allowed anyone else to experiment with the drug, or prescribe it. Meanwhile PDLabs themselves haven't even started Phase II trials yet. I believe that phase I trials are just done to prove the drug is safe. So basically PDLabs has not forked over any money at all for any kind of FDA approval because verapamil was already deemed safe before they created their "patented delivery system," which doesnt work(not to mention they only have a utility patent, no such special delivery patent or special mixture patent). The more and more I think about it the PDLabs thing was a total scam. They filed the patent on purpose, paid off the doctor and never plan to ever release any new information, cause they aren't gathering. They realized it would be a long time before anyone came up with anything to treat us desperate peyronies patients and we'd just keep trying their product. Once someone comes up with something effective, PDLabs will probably just disappear off the map never moving into phase II trials or ever defending their product, they know it doesnt work. As I said in my report they had members of their own company online claiming to have used the product and saying it worked, I simply don't trust them at all. Been using the crap now for over two months with absolutely no softening of my plaque....
The FDA process clearly was made to do well but needs reformed like so many things in government. We need to reform into "smart regulation," as I call it and throw out cumbersome processes and rules for dumb things that only require common sense to figure out.
ComeBackid
If this is a "cure" will the length and grith we lost return to normal, I mean will our penises be just like they were before Peyronies Disease or what? I really hope for a cure, but this has been around for 250 years so I start thinking what makes the next few years special? You guys think this injection could be the answer?
Howcanthisbe,
I've had two theories on the loss of length and girth. Either A. the plaque wraps around the corpus cavernosum, and as the plaque shrinks its squeezes the corpus cavernosum smaller and smaller. or B. The plaque and fibrosis spreads into the corpus cavernosum, making for less elastic tissue to expand. I would say that if the injections really do work and dissolve the plaque and calcifications then if A. is the case one might see a return of some length and girth, however if B is the case, now that the healthy tissue was turned into plaque and you dissolved that plaque, you will see no return of lost length and girth.
Just my thoughts, I may be wrong on both of those theories so who knows. I think there could be somewhat of a return of length and girth, but more so elasticity, if the drug works and if it is ever made available to the public...
ComeBackid
I shouldn't be offering my theories on this becaus I'm not a doctor, much less one of the AA4500 researchers. But since Auxilium won't tell us anything, here's what I think I know.
AA4500 aka Collagenase will break up, digest, metabolize, dissolve - whatever you want to call it - certain types of collagen, including the tangle of misplaced, interlinked collagen molecules responsible for our problem. But it isn't something that will just spread out into an area and get rid of all the collagen in its path. That would be bad, because collagen makes up many structures in your body.
To release a Dupuytren's contracture they inject a small amount of AA4500 into the center of the band. Not enough to dissolve the whole band, or even to sever it - just enough to weaken it but stay confined inside the band. Then they try to snap the band by straightening the finger. This is often fairly easy to do - but the band, now broken in 2, remains in your hand.
For Peyronie's it's going to be more complicated as obviously that simple strategy won't apply. The results will probably vary a lot depending on the distribution and amount of the fibrotic tissue. Maybe they'd have to do many injections of very small amounts - I don't know. Apparently it's been tried by Auxilium and they had enough success to go forward with it. I don't think it will be a 'cure' by any means but in time, as urologists get skillful in using it, it may do a lot of good for many cases of Peyronies Disease.
J,
If what you say is true, and I don't think anyone really knows, perhaps they will need to do injections in small amounts in different places. Perhaps the random injections at different places putting weakening holes into the collagen, combined with an effective VED workout could cause the corpus cavernosum to be strong enough, and the collagen to be weak enough (from the injections) to break the plaque apart.
What about tissue atrophy with this medication? Will it damage healthy tissues like the corpus cavernosum or other skin membranes?
ComeBackid
The Dupuytren's study that I saw made no mention of any side effects, like the atrophy that can result from steroids. However I think bad things could happen if this stuff weren't injected carefully and in the right amounts. It's not clear to me how general its effect might be - what types of tissue it might attack.
Maybe at some point we'll be able to see a published study that answers some of these questions.
Hi All,
This aa4500 sounds very interesting. But, I am still wary of injecting my penis for fear of more scarring. Would it be possible to use this compound with dmso or phlojel to administer it transdermall to avoid the trauma of injections? Does anyone know the molecular weight of this compound?
Cheers.
DMSO isn't a safe or effective way to deliver a drug as you have no control over how far it penetrates. And collagenase would have to be delivered very accurately.
Now that it is proven that TV simply doesn't work, I'd say there is no effective way to deliver collaganese transdermally.
Even if the injections give you a little scar tissue, if the drug works you'll be dissolving most of the scar tissue, even if you create a little new scar tissue you'll have less than when you started, and perhaps the collaganese will break down the scar tissue you create upon injection.
All this is assuming that injections will give you scar tissue, if done properly I don't think they will give you scar tissue from a minimal amount of injections.
ComeBackid
I found some information off the wikipedia on stocks, pricing, and what makes a stock price go up and down. This information could be useful to some on here who don't totally understand the Auxillum stock and why it goes up and down, I'd encourage everyone to check out this information for a good read, and a refresher on how profits will be needed to be shown eventually for Auxillum to survive.
I'm no finance major but I've read a few books, invest myself, and followed Warren Buffet closely. The simplest explanation is to buy a stock when it is low and hold onto it until you think its reached its potentil and sell, sounds very simple, it isnt. Auxillium will not be able to post loses forever, they will have to produce products that work to posts profits (or will they, PDLabs has been earning huge profits, with useless products). If one believe that Auxillium really has had success and will eventually come out with collaganese that works on many conditions including peyronies, they would want to buy this stock immediately at the low price it is and hold it for awhile! They may have a patent on their product eventually and be turning huge profits... or I guess they could turn out to be a PDLabs...
Stocks (http://en.wikipedia.org/wiki/Stock#Stock_Price_Fluctuation)
Stock Price Fluctuation (http://www.indiahowto.com/why-stock-prices-change.html)
Just a dash of cold water.
I remember when an active enzymatic degradation of a disk seemed like a great idea. An enzyme derived from papaya was injected into herniated disks and led to resorbtion of material and decompression of herniated disk against adjacent nerves. Basicly an "easy" discectomy surgery with an injection.
But later it turned out that the areas thus treated were far more prone to arthritic changes.
I would love for a collegenase to be a panacea for this problem - it makes sense that it could. But lots of therapies that make sense turn out to cause harm, or to not work. And the incredible number of false positive results reported from inadequate initial studies in the area of Peyronies Disease research are just amazing. I worry that this may be the same.
Tim
I thought I'd share a little something that I learned Tuesday, July 11th. About two weeks ago I got a phone number from Auxilium's web site. I called that number, and explained to the person who answered that I wanted to find out if Auxililum would be doing more clinical testing. I was transferred to another extension. Naturally, when I got an answering machine, I figured I was getting blown off. On Tuesday I received a phone call from a guy named Gary Nevin, who works for Auxilium. He told me that testing on AA4500 would resume in a couple of months nationwide. He asked if I was still interested in participating in the study. I said yes. He then told me that he would put my name on a list of others who had called him. He only wanted to know my name, phone number, and town that I live in. He told me that there where no guarantees I would be chosen for the testing, but that he would be able to give me "a heads up" on the start date, and location nearest to me, that would be testing. I do know that the testing will be done on patients who have Peyronies and/or Dupuytrens. I can't guarantee that anyone else who calls will get the same response, but I felt that I needed to share this info with all of you. This is Gary's office number: 1-732-223-7321. I did not get any approval from Gary to give out this number, nor did I tell him I was connected to this forum. When I talked to him, he told me that he could not take too much information from me, because he could not appear to be biased towards me in any way. I hope that some of us will try to help with this testing. Hopefully we can help to find that "silver bullet" that we are all looking for. If we don't find it, at least we tried. Keep the faith, brothers and sisters....Blink
Today, July 12, Auxilium filed Form 8K with SEC. See page 20 thru 23 for info on AA4500 used for Dupuytrens. There are before & after color photos of both surgery & injection with AA4500. I don't believe these have ever been seen by the public before. They state pivotal phase III trial to be initiated this year for Dupuytrens & target BLA filing is 2007. As for peyronies see pages 26 thru 29. There are photos of before & after surgery but I did not see any photos of AA4500 use. They state Phase IIb to be initiated for peyronies this year & target BLA filing following approval of Dupuytren's BLA.
Blink,
Thanks for the heads up. I placed a call and left a message. I'll post any response I get.
Mark,
Thanks. I'm going to their site now.
Here is a direct link to that presentation.
http://library.corporate-ir.net/library/14/142/142125/items/204739/auxlpres706.pdf
Page 4 says 2008/2009 as the AA4500 for Peyronies Disease "maturing" timeline
Quote from: Blink on July 12, 2006, 08:52:42 AMBlink
Guys,
I hope it is not lost that a man that is hoping for the the luck of draw on these trials selflessly posted the information for other members even though he knew it would lessen his chanches of selection.
Blink, I salute you!
Truly an unselfish act Blink!
I got a call back this afternoon. Gary said he would put my name on a list and would give me a heads up when and where the trials would start. I felt like he was being honest. I mentioned I was near New Orleans and Dr. Helstrom was at Tulane. He said he did not know if that would be a center for the trials.
I wanted to make everyone aware that I've been contacted and in touch with a guy named Travis Strong via email from John Hopkins. He had initially made a post on the BTC calling for funding and showing a huge interest in peyronies research and stem cell research. Apparrently he has been corrobarating with some medical professionals and may start a research project in the near future on the tunica albuginea graft materials and stem cells. Not much more information beyond this is available but it is certainly some positive news to hear.
Promising contact! ::) Please keep us all informed of any developments with Mr (Dr?) Strong.
Steve
I thought it would be nice to have links to all three related studies. Note the rat research was in 2003. It took three years to catch on.
http://repositories.cdlib.org/cgi/viewcontent.cgi?article=3908&context=postprints
http://www.urotoday.com/browse_categories/erectile_dysfunction/oral_pentoxifylline_may_have_efficacy_in_the_treatment_of_peyronies_disease.html
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14996430&dopt=Abstract
Quote from: Blink on July 12, 2006, 08:52:42 AM
I thought I'd share a little something that I learned Tuesday, July 11th. About two weeks ago I got a phone number from Auxilium's web site. I called that number, and explained to the person who answered that I wanted to find out if Auxililum would be doing more clinical testing. I was transferred to another extension. Naturally, when I got an answering machine, I figured I was getting blown off. On Tuesday I received a phone call from a guy named Gary Nevin, who works for Auxilium. He told me that testing on AA4500 would resume in a couple of months nationwide. He asked if I was still interested in participating in the study. I said yes. He then told me that he would put my name on a list of others who had called him. He only wanted to know my name, phone number, and town that I live in. He told me that there where no guarantees I would be chosen for the testing, but that he would be able to give me "a heads up" on the start date, and location nearest to me, that would be testing. I do know that the testing will be done on patients who have Peyronies and/or Dupuytrens. I can't guarantee that anyone else who calls will get the same response, but I felt that I needed to share this info with all of you. This is Gary's office number: 1-732-223-7321. I did not get any approval from Gary to give out this number, nor did I tell him I was connected to this forum. When I talked to him, he told me that he could not take too much information from me, because he could not appear to be biased towards me in any way. I hope that some of us will try to help with this testing. Hopefully we can help to find that "silver bullet" that we are all looking for. If we don't find it, at least we tried. Keep the faith, brothers and sisters....Blink
I wonder, if a person is chosen for this AA4500 testing, is there a chance they'd unknowingly get assigned to the "control" group who think they're getting AA4500, but are really getting a placebo?
Testing sounds tempting to participate in, but not if there's a chance I'll spend months taking a placebo and experiencing no improvement.
Myrddin,
I know people well that have been in blinded control studies at major research centers. In fact they do not know until the end of the study which group they were in. In fact the doctors do not know if it is a double blind study. At the end of the study they are given the test drug for free. It does involve more travel however. If it is not double blinded and you have to travel a long distance you can hope for some consideration.
Since I am not sure that the AS4500 studied are blinded, or if they even have a control group, this may not be an issue. I think injecting a placebo into ones penis my have serious ethical prohibitions but they could use a control like Verapamil.
The surrent standard of care for the ethics of such studies is that the control group gets current standard of care therapy (and a placebo, if it is needed), and the intervention group gets the same PLUS the study drug. For those studies that cannot be blinded (ie a surgical intervention versus what?), then the comparisons are usually made to either historical controls or a similar group followed conservatively.
The advantage of participating is such a study is that one should get a lot of close evaluations. If one is seen to be getting worse, we will often break out of study mode, and treat them with more aggressive therapy and to hell with the control crap. A recent study of mine was discontinued because all the patients were doing so well that we felt it was unethical to continue to give placebo. We aborted the study and put everyone on therapy, and just wrote it up.
Tim
One thing that I know about the AA4500 testing is that it is in phase two. I believe that they concluded that the drug is effective, but need to work on dosage levels under a controlled environment. At least that is what I gathered by reading the report that was out a couple of months ago. If this is true, then wouldn't all of the test subjects be getting the real thing? Keep the Faith...Blink
Who needs a STUDY??- Take 10-12 men in different stages - and just do a before and after- what are these giys waiting for????????
Hopeful.. I say contact them and open a clinic in the Bahammas- or Canada- anywhere- let's just get it going- enough is enough- Their drug is an enzme- what I have been saying all along.. look at their report....
Quote from: Hawk on August 11, 2006, 10:14:28 AM
Myrddin,
I know people well that have been in blinded control studies at major research centers. In fact they do not know until the end of the study which group they were in. In fact the doctors do not know if it is a double blind study. At the end of the study they are given the test drug for free. It does involve more travel however. If it is not double blinded and you have to travel a long distance you can hope for some consideration.
Since I am not sure that the AS4500 studied are blinded, or if they even have a control group, this may not be an issue. I think injecting a placebo into ones penis my have serious ethical prohibitions but they could use a control like Verapamil.
Hopeful,
I understand your frustration about the way drug studies are performed. No reputable drug company would do what you suggest, for several reasons.
First, the ethical standard regarding investigational trials pretty much mandates a control group in addition to the study group. See Tim468's post on 8/11/06 on this forum for an excellent example. Second, the drug company would be undertaking a huge liability in departing from the norm; suppose they gave the drug to 10 or 12 men, and severe medical problems of some kind ensued. The fact that they did not follow the standard protocol--developed in medicine over many, many years--would be the cornerstone of the legal case against the drug company, and no number of "airtight waivers" by the participants would undo this liability. Third, the FDA would never approve the drug without a closely conducted and monitored study, and FDA approval is what would allow the company to mass-produce and market the drug. And without FDA approval, we can't get the drug. Also note the many drugs that do go through this process, are approved, and then cause medical problems later. The studies are meant to minimize the chances of this happening (but they do happen from time to time anyway.)
Again, I wish it could all be simpler, but we live in a world of rules, and probably that is better in the long run. My penis may have its problems, but I still don't want it to fall off from an under-researched drug!
Auxilium Pharmaceuticals announced today that they are opening a 2d manufacturing facility for AA4500 (collagenase) in Pennsylvania. The other facility is in Keele, UK and they have not decided yet if it will remain open.
Hey Guys,
Here is the link with the information Mark is referring to concerning AA4500:
http://phx.corporate-ir.net/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=901685&highlight=
Keep ya head up. Help is coming soon.
Power
They ain't making AA4500 out of the goodness of their heart. Here is what they say on the web site:
- Highly motivated patients - many paying cash for surgery or other treatments.
- We expect AA4500 should command a premium price.
Get ready for another miracle treatment that may not work at all (my cynical side coming out after years of the next best thing being not so great).
Tim
-
Hey Tim,
You believe this new, and most probably expensive treatment will not help at all in any dimension? The science behind it seems to be solid.
Power
I think it might work if you use it with a VED:) if you remove the plaque you still have a underlying issue with the elasticity of the tunica, remolding it.....mechanical....oh that's right, there isn't a public company selling VED...no stock hype!
By the time they get it to market and figure out how to get it in a rat's dick I'll be pushing up Daisy's, I order my ved today. Which is a pain in the you know what in itself, insurance wouldn't cover it, plus it takes a week to ship ect....
I was reading a post on a uk site today, they said it was the first choice in Europe and Canada, they suggested getting a small one and large one and to use them for up to 15 minutes a day like exercise, not much of a protocol to follow, but it seems more people agree with this method....
I wish I could have hope in AA4500, I just don't get warm and fuzzy about it at all.....how could I get my lost size back from this? Maybe someday it will help along with a mechanical approach, I do believe maybe this mix approach...Medicine and Mechanical might someday help.....
The real problem as I see it is that they can't get the rats to pump there dicks yet with the VED....
Reminds me of a old joke, you know how you keep a dog from humping your leg?....you pick him up and blow him.... so if a broker calls me and asked me to buy there stock, I will tell him to go blow a Rat:)...
Rico
:D :D :D I'm getting this mental picture of a technician trying to use a little-bitty VED on a rat strapped down to a table --- can't stop chuckling ;D ;D ;D
Steve
I think that AA4500 makes sense. A lot of therapies have made sense - vitmain E and PTABA make sense. Verapamil makes sense. Pentox makes sense. All the anti-inflammatory therapies make sense. But as of yet none of them have been completely helpful.
What I hope for someday is a biochemical individuality screen that allows us to tailor our care to our individual requirements. Someone may have an autoimmune disease and need immunomodulation. Another may have a one time injury and simply require surgery with no need for worrying ever again. Who knows?
I really hope AA4500 works. But I recall vividly the hope around the use of Papain for herniated disks - how this enzyme from papayas was supposed to simply dissolve away the herniated disk. It worked great - except that Chymopapain was abandoned as a technique because of numerous reported incidents of transverse myelitis and anaphylactic shock.
Collegenase has been used to dissolve herniated disks with mixed results.
I hope this drug works. History suggests it may not be a silver bullet for everyone.
Tim
Tim and others,
What we are forgetting is that this drug isn't just being made for peyronies disease exclusively. I don't know if its a good sign that they are opening a new manufacturing facility right here in Pennsylvania or not, since they might be closing the old one in the UK, I suspect they may be doing this to save on shipping costs more than anything. Still it is a good sign that they are moving ahead with the Phase II trials or whatever, starting supposedly this month or in October. I mean eventually this company will have to start turning a profit or go out of business, I don't know how much longer than can poke around without turning a profit at all. I know a few of us on here have gotten on the signup list for the trials, hopefully at least one of us will get selected, then we can get an update on how well this drug works.
Tim,
That post was right on the mark as I see it. Individual requirements....I read a post by Dr. Levine talking about two classes of peyronies....one being the injury and the other a underlying vascular problem that effects the whole tunica....which seems also to cause ED...
With the medical community not being on the same page also makes one doubt any medication, one says pentox, one says something else....the recent VED studies seem promising for people with a condition I have, more of the injury, although then again, it is on the septum, this could be in a class by itself as would someone with it close to the glands.....
AA4500 I don't believe will be a silver bullet for all of us, I guess if it can help some than that would be good or used in conjunction with other treatments......I wonder how it will react to pentox or if they will say if you have taken pentox or drug x in the last year don't use it, who knows....
I will try to find the site and post it, it was a peyronies forum from the UK, some of you might have seen it, this one is better, but I thought the comments on VED were good.....there thoughts were the same, but not as detailed in protocol, just said, buy a small ved and buy a medium one and interchange them using low neg presssure for a short period(seconds) and then do this for 15minutes like exercise and they were having good results..... But like Tim said, we are all different and this plan might be good for the "A" typical peyronies.....
God Bless,
Rico
FYI...definitions of trials/phases:
A Phase One trial involves a small group of participants who test the drug or procedure's safety, possible side effects and proper application or dosage. Initial participants receive the actual treatment, whereas participants in Phase Two and Three trials might receive a placebo
"Subject line on this post edited for easy reference"
Thanks for the insight on the clinical trials!
I looked back on your previous post in January and saw you were considering surgery. Please give us an update :). I hope you are off the potaba by now (yuck!)
Welcome Back!!!
Liam
Who has signed up for the auxilium trial? I talked to the coordinator myself a couple of months back and was not impresses. How many treatments are they planning or as I seem to remember is it a dose ranging trial with multiple treatment arms? Is there a placebo arm?
Kenm,
I know at least 4 people on here have signed up, Blink is the man who got the contact information for Gary Levin I believe his name is. We all owe Blink a HUGE thanks, this is a guy that willingly decreased his odds of being selected for the trials by telling others.
As far as what Blink and I can tell there will NOT be a placebo in this study, this is phase II and they are working on trying to find out the correct dosage. This leads me to believe that some people will get more injections than others and some may get higher dosages, as they try to work on the proper dosage to treat peyronies.
Who did you talk to that you weren't impressed with? I talked with Gary, I mean he seemed pretty normal happy to take my info down, I don't really care what the coordinator is like or if he isn't exactly mr. sunshine ;D ;D ;D ;D, as long as the drug works!
Liam,
I am holding off on surgery after reading more articles on the down side. I have also seen some pictures of the surgery and that is enough for a moment of pause.
I have recently been trying some of the lotions, potions and pills recommended by Dr. Herazy of the Peyronie's Disease Institute. A little early to tell if it will help.
I have also called and awaiting a return call from Gary Nevin about Phase II testing. I only live a couple of miles from Malvern, PA.
Ramjet
This from SEC filing today: FDA has requested local effects/tolerability pre-clinical study of AA4500 outside of plaque. Study to start by year end. Phase IIb moved to 2007. Auxilium has an audio webcast this AM and perhaps more info will be released then. I believe it's at 10:30AM CDT. These webcasts usually remain on their website for a couple of weeks.
Wow,
This does not sound like good news? So the FDA would like a pre clinical study before they can begin the trials they planned to start this month or next. I thought safety was an issue to be determined in phase I? Seems like this will only slow down the process by a few more months. There should be plenty of data on the tolerability of collaganese since it is used for other stuff as well. Man this is not good news, Auxillium will have to wait even longer now before they can turn a profit. I don't know why the FDA would demand this pre-clinical study unless they felt that there was an issue of safety with putting collaganese in the penis. Maybe Tim can give us a few comments on this or someone whos well educated in the FDA process.
ComeBackid
ComeBackid,
You are right! This product won't be to market for a long time! Then remember you have phase three...if they run out of rats or you get to be part of the trials...then you might get a shot at it....and then does it even work......I don't feel this is something they are focusing on peyronies anyway, it is a spin off for other uses, add to the stock hype...they need money to fuel the rocket....these projects are a beast, they eat the funds from the public equity markets like wild fire...they will almost say anything to get more funds for research....
I keep coming back to reading so many post that the plaque goes away but the underlying issues don't, lost of size, elasticity ect....
I don't want to come across negative on AA4500, but hoping for this to be a silver bullet seems like a slim bet to me....just look at verapamil and Peyronies Disease labs.....all the research ect...
I will say I think it is good that these trials are out there, and I think the FDA does need to step in to make sure this drug is safe......and maybe it will help people in the future and be more help for specific peyronies classes of the condition....I just can't sit on my hands or have false hope about AA4500.......do the math...resume phase ll in 2007......and that will get push to what and then phase lll, when? 2008 and FDA looking at it more....how many years of study?
Best regards,
Rico
The pre-clinical tests that the FDA wants before Phase IIb starts are to begin this year. These tests will be done on animals and are to last for 13 weeks. If all goes well the delay will only be a little more than 3-4 months. AA4500 for treatment of Dupuytren's (contracture) Disease. Phase III trials are still on for 2006. One injection has worked for 70 percent of patients with the average being 1 1/2 doses. Some patients have required 3 injections, each injection being followed by a 30 day wait w/manipulation period. They expect application for approval to FDA for dupuytren's in 2007 & market launch in 2008. They expect to apply for FDA approval for Peyronie's after the OK is made by FDA for use w/ dupuytren's. I was hoping that they would show before & after photos of AA4500 use in peyronie's disease in their SEC filing today but they are still not releasing them. In SEC filing they did show before & after photos of AA4500 use with dupuytren's. Go to www.auxilium.com then to Investor Relations & then to SEC Filings. Look for Form 8-K of Sept. 7, 2006; then to page 22 for photos.
Dear Forum members and guest,
I just read the 8k and you can download it by going to yahoo finance and putting in the stock symbol AUXL ...... it is a good report in power point format.... the drug testin is interesting and might be something for ED to look at if you can take testrone, it is a gel....
2009 is the launch date for peyronies..... so it is a way down the pike....I think that they are doing studies is promising and could lead to other developements with the diesease...
When Prince said in his song "I'm going to Party like it is 1999" well I guess I have to sing "I will be pumping my ved till 2009"
I want my MTV I mean VED Oh well, I wish I could say that I'm excited about the 2009 launch date to market, but it seems like a long way off....
I am interested in there topical gel, Testin for ED....
Rico
Since Pentox has received a lot of attention here. i started digging in a bit in the realm of TGF beta regulation. To say that this field if complicated is an understatement. Imagine driving on the LA freeways at rush hour for the first time in the dark wearing dark sunglasses - it's about that easy to navigate this territory. One particular risk is that a drug that modifys something (ie Transforming Growth Factor Beta, or TGF-B) is that it may also modify something else - and not for the better.
With that in mind, I found a few interesting ideas in the realm of Dupuytren's Contracture (DC) which is NOT the "same" as Peyronies Disease, but is similar in some basic mechanisms, and many of us have both.
Here is the first article regarding Imiquimod cream (which I do not know if it is available in the US):
*******************************
Namazi, Hamid.
Institution Department of Orthopaedic Surgery, Shiraz University of Medical Sciences, Chamran Hospital, Iran. namazih@sums.ac.ir
Title Imiquimod: a potential weapon against Dupuytren contracture.
Source Medical Hypotheses. 66(5):991-2, 2006.
Abstract Dupuytren disease is a proliferative fibroplasia of the subcutaneous palmar tissue, occurring in the form of nodular and cords. Evidence is certainly accumulating for raised levels in Dupuytren's tissue of growth factors known to stimulate fibroblasts, Interleukin-1, basic fibroblast growth factor, transforming growth factor-beta, prostaglandin-F2, prostaglandin-E2, platelet derived growth factor and connective tissue growth factor have been suggested to have a role. Immune modification of profibrotic cytokines would provide a novel means to treat dupuytren contracture. Imiquimod cream 5% (Aldara) is an immune modifier, that downregulates transforming growth factor-beta and fibroblast growth factor-2 (the two most important cytokine in producing fibrosis). Based on previous mentioned evidence we suggest: imquimod as a potential drug for dupuytren contracture treatment.
Text
A major challenge of contemporary medicine is to break the traditional compartmentalization that frequently separates various fields. Unexpected linkages between various areas of medicine are indeed of particular interest.
In this paper, the aim is to enlighten the hand surgeon colleagues about the recently discovered
immunomodulatory effect of imiquimod in order to encourage research on the use of this safe agent in the treatment of Dupuytren contracture. Dupuytren's disease is a condition of the hand
characterized by the development of new fibrotic tissue in the form of nodules and cords [1]
The site of onset is the fibrofatty layer between the skin and deep structures of the palmar
surface of the hand, which had a precisely ordered system of subcutaneous ligamentous fibers.
Transforming growth factor-beta (TGF-b), Platelet derived growth factor (PDGF), Epidermal
growth factor (EGF), Interleukin-1 (IL-1), Interleukin- 4 (IL4), Interleukin-6 (IL-6), Oncostatin M (Osm) and Tumor necrosing factor (TNF), have been demonstrated to regulate fibroblast proliferation and deposition of extracellular matrix in vivo and in vitro [2].
Transforming growth factor-beta (TGF-b) is a key fibrogenic cytokine that has been shown to
stimulate fibroblast proliferation and extracellular matrix deposition [3,4]. Evidence is certainly accumulating for raised levels in Dupuytren's tissue of growth factor known to stimulate fibroblasts. IL-1, FGF, TGF-b, PG-F2, PG-E2, PDGF and CTGF have been suggested to have a role [5–8]. Alioto et al. [9] in an experimental research exposed cells of both the normal palmar fascia and Dupuytren fascia to FGF, TGF-b, PDGF, there were quantitative and qualitative differences between the cell types, with Dupuytren contracture being more metabolically active and more sensitive to the growth factors tested.
Immune modification of profibrotic cytokines would provide a novel means to the Dupuytren contracture. Imiquimod is a low molecular weight imidazoquinoline that has been approved under the registered name ''Aldara'' for the topical treatment of Human papilloma virus induced warts. Its capacity to boost immune responses via the induction of cytokines in the treated lesions encouraged several authors to use the drug for the treatment of skin cancers [10].
Imiquimod cream 5% (Aldara) is an immune response modifiers that has demonstrated antiviral
as well as antitumor activity both in vivo and in vitro. It induces the cytokine IFNa, IFNc, TNFa,
IL-1, IL-6, IL-8, IL-10, IL-12 and it stimulate cellmediated immunity (TH1 Pathway). IFN-c is a TH-l cytokine that downregulates expression of TGF-b. In addition, it possesses an ability to suppress the TH2 pathway including profibrotic IL4 [2,11].
In an experimental research Hesling et al. [10] measured FGF-2 level in skin biopsy before and after imiquimod application. This study reveals that FGF-2 level decreased from 100% to 24% after imiquimod application. Based on previously mentioned data we suggest, imiquimod as a potential drug for dupuytren contracture contracture.
It is believed that the attempt to enlighten the hand surgeon colleagues about the recently discovered immunomodulatory effects of imiquimod stimulates a multiplicity of investigations on the utility of these agents in Dupuytren contracture, leading to provision of better treatment to patients suffering from this conundrum.
********************************
Here is the second such article - much briefer and more speculative:
*******************************
Simvastatin may be a useful therapy in Dupuytren contracture
Hamid Namazi, and Mohammad Jafar Emami
Department of Orthopaedic Surgery, Shiraz University of Medical Sciences, Chamran Hospital, Box 71324, Shiraz, Iran
Available online 15 December 2005.
Dupuytren disease is a proliferative fibroplasia of the subcutaneous palmar tissue, occuring in the form of nodules and cords.
Evidence is certainly accumulating for raised levels in Dupuytren's tissue of growth factors known to stimulate fibroblasts: interleukin-1, basic fibroblast growth factor, transforming growth factor-ß, prostaglandin-F2, prostaglandin-E2, platelet derived growth factor and connective tissue growth factor have been suggested to have a role. Immune modification of profibrotic cytokines would provide a novel means to treat Dupuytren's contracture [1], [2], [3], [4], [5], [6], [7] and [8].
The 3-hydroxy-3-methyl glutaryl coenzyme-A (HMG-COA) reductase inhibitor (simvastatin) reduces atherogenesis and cardiovascular morbidity. Moreover, there is evidence that simvastatin has immunomodulatory activities, that downregulate transforming growth factor-ß (the key cytokine in producing fibrosis) [9] and [10].
Based on previously mentioned evidence we suggest, simvastatin as a potential drug for Dupuytren contracture' treatment.
*******************************
Food for thought.
Tim
I don't want to burst anyones bubble on the AA4500, and who knows, maybe down the road five or ten years this will help someone....bottom line is that 2009(right in documents 8k), is the roll out projection for peyronies....and from there track record...2009...should be 2011.....the stock went up because the people who go into this at the higher price are cost averaging down now...there will be a sell off soon, and it will slide again....someone will have to show me how this will add elastic properties to the tunica to make me excited about it...
Rico
Dear forum members,
I down loaded the articles from the AUA conference this spring, I was looking for something on Levine and his VED protocol....I did stumble on this company and there new drug...
Now they are developing this of ED....but it to me would be promising for anti fibrosis and peyronies....
There web site i www.surfacelogix.com the drug is slx2101....very interesting....
Now do to the fact that Viagra has become a house hold word...and there is big money behind this, and they stumble on it looking for a high blood pressure....
Well it looks like know everyone wants a piece of this billion dollar market...so the research dollars are there...just look at this product......I really believe they will find the cure through the back door of looking for ED....blood flow...oxygen....slx2101 anti fibrosis....this along with VED could be the ticket...they are in phase two already....
Rico
Rico, that is really a great find. When one goes to pubmed and does a search on "rock inhibitor", it is enough to make one ecstatic. These people may beat the collagenase purveyers to the solution to peyronies AND cardiovascular disease, not to mention a string of other degenerative diseases. So "Rho-ROCK" is yet another promoter of fibrosis, along with blood flow issues, inflammation, pde-5, etc. AND they are working on PDE-5 as well! This is just so outstanding!
Yes George I agree....this I feel is huge for peyronies....once again the market is so large for ED..the funding is there, plus the FDA has already clear the path for several of these pde-5 inhibitors, they will move much faster and if anything it can only put more heat on AA4500 to get to market.....
What I like about these drugs is that the delivery is already there, oral, so no more trauma to the penis...and also the compliment with the VED...another ED devise that has been used in a off label sort of way(no restrictson ring).....this company is big in anti fibrosis....which is in essence anti ED..... or could be anti peyronies... good stuff....
I going to read up on Rho-Rock tonight, thanks for the information...
Rico
George,
If you look at one of there other drugs, which should be at market soon, in trails, is slx-2119 (rock2) for inflammatory and fibrotic inhibitor..... I like it that they are also coming out with the slx2101....very interesting indeed...
Rico
Rico, you are so right! A good ORAL antifibrosis drug would really be cool for a lot of different diseases INCLUDING PEYRONIES. We need the right pills to put the surgeons out of business in this field! That would really increase quality of life for a lot of folks. And what impresses me most about this company is their sweet low profile. While BioSpecific has been marketing collagenase for how long now??? with still nothing to show for it, here we have a company that by the time we discover them, they are already quite aways along with their trials. So cool! I really seems like they are staffed with really sharp people and are more into pharm technology than into PR. Isn't that a pleasant change. About 180 degrees from Peyronies Disease Labs. Yes, this is good news. This is very good news!
One can google the terms Pirfenidone and TGF. It is a new anti-fibrotic agent that reduces inflammatory markers and improves lung function in Idiopathic Pulmonary Fibrosis (IPF). It blocks lots of bad things and it's effects include reduc ing TGF activity and promoting arginine pathways (didja know that TGF increases activity of "arginase" which reduces available arginine donation of NO?).
http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1600-6143.2005.00876.x?cookieSet=1#search=%22Pirfenidone%20%20TGF%22
This is a new thing on the horizon. The study in Japan was stopped at 9 months because the study patients were doing so much better than the placebo patients that it was deemed unethical to continue. Pitt is doing a newer study in the US on Pirfenidone and seeks to reproduce the results of the Japanese study.
Looking (as I have been doing) for alternative ways to reduce TGF-Beta activity, this is pretty exciting.
Tim
Wow the new treatment sounds promising hopefully they will get it to market, unlike Auxillium is doing... Has anyone heard when they will start their safety test and when it will be done? They were supposed to be doing trials in September, could this be another fluke, sure sounds like it to me.
They are a private company, were listed as a red herring top 100, which is very good, there are funded by venture capitalist....a whole different animal, not some stock hype crap.....some sharp people in this group, they are out of bean town, Harvard research....I like it....three billion dollar market with ED, and they are also researching fibrosis and inflammatory dieseases...when you have people trying to break into this market and make a better drug, you have to remember that ED also is something that is associated with scar tissue or hardening of the tissue from non use, so it makes sense to address this issue, and back into a cure or aid for the betterment of peyronies...
The baby boomers drove the SUV market, the computer market, and one thing they will all want is a good erection, and they will pay for it, they are only 30% of the population but 50% of the GNP...they have the wallet, this peyroines is a baby boomers diesease which is good for the funding of a cure....ED is are friend...I believe it will drive the process to find a cure for peyronies....blow flood and oxygen discoveries could find the cure for fibrosis.....
Rico
Does anyone know when they have rescheduled their clinical trials for? Or when the safety "test," will begin? The excitment that was starting to build around this company seems to have died off on this forum.
Also here is a link that was passed on to me from one of our forum members, any thoughts on this... Tim... others etc..?
http://www.findarticles.com/p/articles/mi_m0PDG/is_4_3/ai_n12417025
Hey Guys,
Came across this while researching gene therapy and reversing fibrosis. I think it is extremely worthwhile to forge a relationship with these guys from the Charles Drew University of Medicine and Science. Dr Thomas R. Magee Ph.D. is currently involved in developing gene therapy vectors for therapeutic uses in urology in particular, treatment for peyronie's. More information can be found by clicking the link below:
http://www.cdrewu.edu/cosh/biomedical_sciences/mcgee.htm
Kind Regards,
Power
AKA, "Gonna beat this crap!!"
Whoa Power! That is so cool! And did you note what he refers to as to the cause of Peyronies? Repeat injury! Same thing as I've been thinking and saying for a long time now. Thats what causes Peyronies to go in and out of 'active' states and why I'm so into maintaining control over inflammation. The problem with Peyronies is that it makes the penis so terribly susceptable to further injury both physically and biologically (lack of blood flow etc.), and once you get inflammed the scarring process is reignited all over again. But we know that delivery of nitric oxide at the right time in the right amounts is the solution and it looks like these guys are all over that equation. Hopefully the top uro's are following this work and will be ready to deploy it as soon as it becomes available. But what a great find and a great read! Thanks for posting it!
- George
Magee works in the lab of Gonzalez-Cadavid at UCLA. Gonzalez-Cadavid is the one who has done a lot of the best in vitro work with TGF and pentox (on rats), and now pentox in humans.
This is the anstract that caught my eye:
Davila HH, Magee TR, Vernet D, Rajfer J, and Gonzalez- Cadavid NF. 2004. Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease. Biol Reprod. 71(5):1568-77.[abstract]
Very exciting - but remember that an adenoviral vector (using adenovirus that was "inactivated" so it can't cause disease) was what was used in the muscular dystrophy experiments in Philly that ended up with a kid dying. So, I think we may have a way to go before we see a clinical application in humans.
Tim
Wow, Glad you posted that article Power, that article gives me a lot of hope and looks promising. Someone from our forum should contact Professor Magee. As we continue to work at Peyronies Disease awareness we will see more and more researchers showing an interest in this disease. It seems to help when ED and Peyronies Disease are kind of packaged together, as so many people have ED and there is a financial interest to develop a cure. I would remind everyone on this forum we are not getting the job done in the Peyronies Disease awareness arena, and there is much work to be done. If one has an interest in helping out they might try PMing Blink, our acting director of Peyronies Disease awareness for the time being, we do have some good ideas and exciting projects started and need motivated people to continue to work hard. This article is amazing, its good to see some people out there know what Peyronies Disease is and are trying to help us sufferers.
ComeBackid
For more on the problems Tim is referring to with using viruses in gene therapy, read this:
http://www.ascribe.org/cgi-bin/behold.pl?ascribeid=20061005.193442&time=07%2052%20PDT&year=2006&public=1 (http://www.ascribe.org/cgi-bin/behold.pl?ascribeid=20061005.193442&time=07%2052%20PDT&year=2006&public=1)
It eloquently elucidates some of the issues that stand in the way of bringing a product like this on the market >:( . So for now, Pentox looks extremely promising.
- George
I was surfing and reading the urology news, look at the old report by lue, the one Hawk linked to the forum....I looked at new news and Oct. 4th, 2006 they had a article on off label use for iphe5 inhibitors...they did mention that they were looking into off label use for peyronies....
Rico
BTW, the DNA treatment described below was not done useing adenovirus, but a "plasmid" dna (think spare change in your pocket)
Tiu
I wonder when the doctors where trying the new ED drug, the pentox and viagra mix if they shot the rat dick with the new wonder drug and when then look under the magnifying glass they saw the rat's dick scar tissue had improved and looked at each other and hoist there beers and said "Brilliant" peyronies disease cure.....now remember we were looking for the tbg wxyz.... Oh the stumbling tumble weed....how sweet it is.....
I am glad that the baby boomer's want to stay hard...there is a cure on the way....5000 people turn 50 everyday.... pretty soon we will say, well I have a form of ED, it is cause by scar tissue, no big deal though, I just take two penviagine pills a day, and pump my dick a couple times a week...
Most doctors don't like to admit that they stumble onto many cures, it makes them look like pragmatic inventors, but lets face it, in business or music, cooking ect...most of it comes about by accident....you throw enough things agaisnt the wall and something will stick, put something in though little dishes and wait, something is going to happen....and they have lots of rat dicks, no one loves a rat.....I think we should make him are mascot....we have more in common with them than we know....I have the dmso in my cupboard to prove it:)....Long live the Rat!!! If they keep sticking needles in the rat's dick to cure ED, this is going to keep making scar tissue, once they hit the mix where there is no scar tissue, we will be free....Brillant!!!
Rico
Tuesday Oct.17,2006 urotoday....
Urotoday go to ED section new article out today on results of the first human trail for Gene Tranfer...treatment of ED....this is suppose to be the "Holy Grail" for disease.... this could be very postive for peyronies....
Rico www.urotoday.com
Today Auxilium announced plans to reallocate resources to its lead development project AA4500 (for Peyronie's, Dupuytren's & adhesive capsulitis) after discontinuing development of another drug (TestoFilm). Their CEO stated "AA4500 is a company changing product opportunity that is our top priority".
Drop back down a little in this thread and you will find a discussion of the gene therapy subject, followed by a critical analysis.
- George
Mark,
Thanks for the update, I think many of us are anxiously awaiting the arrival of this product from Auxillium. Do we know when they will start these "safety," tests that the FDA is requiring? Do we know when the Phase IIB clinical trials have been rescheduled for that were supposed to start this past September? I wonder if this will push the marketing date back, or if Auxillium takes these things into account when they say 2007-2008? Nonetheless this announcement is definately good news, I don't see how it could be bad, lets hope they keep the trials moving along here.
ComeBackid
In a press release today, Auxilium released for the first time detailed information about methods & results from completed phase II trials. (Study A & Study B). Both studies were open label & up to 12 months in duration incl. follow up. Clinical success is being defined as change from baseline in deviation angle of at least 25 percent. Dr. Gerald Jordan was lead investigator. He is professor of Department of Urology, Eastern Virginia Medical School. These results have been presented at the American Urology Association meeting in Maui, Hawaii. Dr. Jordan states that the drug AA4500 not only reduced penile curvature but also eliminated pain on erection & increased sexual enjoyment & satisfaction. In these studies, treatment with AA4500 resulted in 89 percent of patients who received a 3 treatment series of 3 injections each achieving clinical success. BioSpecifics Technologies Corp., licensor of AA4500, sponsored and monitored the trials. Auxilium plans to comence by the end of 2006 a pre-clinical animal study on the local effects and tolerability of AA4500 injected outside of the pl aque. Auxilium expects to begin a phase IIb dose optimization trial for Peyronie's Disease in 2007. An additional key element of this Phase IIb trial is validation of a patient questionaire that will include data on the impact of AA4500 on improvement of sexual quality of life. These data will be used to support the primary efficacy endpoint inPhase IIb. There are more details on Study A & Study B in the press release. For those details go to www.auxilium.com & find Investor Relations. It is on page 1 & the lst item under RECENT NEWS.
Wow,
Mark I signed on today expecting to read more of the same on supplements, this just made my day. So apparently 89% of patients achieved a reduction of at least 25% in their curve, lessening of pain, and improved sexual satisfaction, this clearly means this drug works unless there is a catch I"m missing, in fact this means this drug works for 9/10 people and would be the highest efficacy reported on any peyronies treatment up to date. Wow this has to be GREAT news, I think some people thought they were stalling on the AA4500 as a treatment. I'm sure this will cheer a lot of people up, the question now is, how soon will us sufferers be able to get access to this treatment for peyronies? Do we have anyone on the forum that participated in this study, Gerald Jordan is located in Norforlk, Viriginia, so I would imagine all the patients in the study were from south east virginia?
ComeBackid
Hey Mark 501,
Thank you for staying on top of the AA4500 developments.
You always seem to post at the right time. Very refreshing news.
Power
I'm not trying to bum anyone out,
Rico
[/quote]
Rico
Very critical.. and a tad bit negative indeed. I'll still continue to hold on to the drug's promise. I know it does not appear to address your buckling scenario, but I am quite sure the minimal results of 25% reduction in curve (as you put it) is a big deal for some; perhaps many.
Power
FDA regulations will require that future trials MUST include other doctors at other locations, most likely in other states. I believe that there will be multiple locations. These other locations will depend on the level of interest by both doctors & patients. Chicago & Houston are provisional candidates. The number of patients participating in trials should increase quite a bit in the future, especially phase III. For those accepted in trials there wont be a wait until 09 or 10.
Kobold,
You ask a great question and make an excellent point. Curve is the result of one thing, one side being shorter than the other. There are only two ways of reducing a curve: lengthen the shor side, or shorten the long side. Clearly AA4500 does not do the latter.
Hawk,
How do you interpret the study result then. Was the reduction in curve spoken about not real? I am lost. The auxilium reported stated a 25% reduction in curve from the use of AA4500 in the study.
Power
I have no qualified response except to say if you reduce the curve of a penis, or a piece of wood, you lengthened one side or shortened the other. That is plain geometry. You may do something in addition like lengthen both sides but lengthen the short side more. That still leaves the fact that the short side was lengthened. The only way to lengthen that side with AA4500 is to return elasticity to what was once not elastic. The lack of elasticity is what reduces erect penis size and shape. Anything you do to reverse this must restore shape and size, at least to that degree.
Kobold,
I can describe "buckling" best by describing my own penis. I have a normal erection from the base of the penis to a point about two-thirds of the way out; at that point, the Peyronie's plaque on the top and both sides of my penis causes a narrowing very much like the shape of an old-fashioned milk bottle. That last one-third is not nearly as hard when erect, and can be easily moved back and forth. In other words, it "buckles" at that point, similar to a metal rod with a weak spot in it.
The good news is that the combination of L-arginine, trazodone, and pentoxifylline (pentox) are working for me. The quality of erection has improved significantly in that distal one-third, and for that I am very very grateful. I still have an upward curve that was not present before Peyronie's, but it is not terrible and not bothersome to me. I don't know why this combination works, but results are ALL that counts!
Scott
Great news, Scott!
The Auxillium stuff has me a bit wary. I note that the trial was open label, meaing it was not blinded or controlled. I also note that the news includes info that the drug will be tested on animals in what sounds like a safety trial - which usually has to precede a clinical trial. All of this makes me wary, since I have worked with reputable companies and not seen such backwards ways of bringing a drug to market. Also, the dropping of "Testim" is worrisome - about the financial soundness of the company.
The results sound promising to me though. As someone who has had a chronic condition that occasionally worsens, I am more interested in reversing the mechanisms that cause Peyronies Disease, than I am in fixing the results - for what is to keep the "results" from coming back in the not too distant future?
I have also seen some promising surgical techniques dismissed as unlikely to help since the lesions recurred after an initially very good to excellent result (some of the SIS (submcosal intestinal serosa)studies showed great results as a "patch", only to show recurrence of lesion within 6 months)(I would also note that some of the more optimistic "results" in the surgical literature did not include such long(er) term followup). An excellent styudy out of Seattle showed that using the VED post-op prevented the reoccurance of scarring or placque (in THAT study).
Hopefully we will develop surgical and medical therapies that "fix" things, followed by medical therapies that *maintain* good tunical health (such as using the VED and adding arginine or Pentox), allowing these therapies to make you better and then allowing you to STAY better.
Tim
For what it's worth:
Gerald Jordan is perhaps the best on this planet in genitourinary reconstructive surgery, and is known and teaches worldwide. He is not about to publish or report on anything that varnishes the truth to line his pockets. I put nothing past Auxillium, but I trust what Jordan reports. Keep in mind that he is a cutter, and the development of an injectable drug does not play to his benefit.
Hawk is exactly right, reduction in bend comes from return of elasticicy.
Larry
Quote from: Rico on October 29, 2006, 06:50:32 PM
The curve or reduction of bend can be from return of elasticicy, but also from the reduction of inflammation....
Rico...
Rico, Please expound on how reducing inflammation on the short side of your penis where the scar tissue is actually makes that side longer than it was with inflammation IE: support that statement with expert opinion, studies, or in depth explained theory.
Rico, Your remark about Dr. Jordan was nothing short of slander. There is no excuse for this kind of behavior on this forum.
In the first test it appears patients were given 2 sets of 3 injections, in the second test it was bumped up to 3 sets, this seemed to increase the success rate from 53% up to 89%, so it seems as if they are still playing around with dosage and how many injections one needs, this is ok though, they are working out the kinks. I think overall this is positive news. Rico I do agree with you that some things are vague in the report, for example they could of reported what the reduction in deviation angle was for those patients who achieved greater than 25% reduction. It would of boosted the credibility of the report and showed more impressive results if they reported the handfull who achieved say 50% in reduction, if indeed they saw results like this. Some of the things they are measuring in this report are pretty vague, what is " increased sexual enjoyment and satisfaction?"
However this really shows us something I think, when I look at the second study I don't see it as 89% achieving success, I see it as 100% because 8 people achieved a reduction in curvature of at least 25%, but the odd person did achieve 24% reduction in curvature as well. That means for the 3 series of 3 injections collaganese injections did something to the plaque in everything. Some have said this could of been the needling. If this was the case we would see more people who have verapamil injections done seeing improvement. My doctor reported to me 40% of his patients see some improvment. Our own PDS survey I believe didn't even show 30% of the people who got verapamil injections saw improvment. If collaganese was not working and it in fact was the needling, then verapamil injections in my opinion should produce a similarly high efficacy rate. To me it looks like the collaganese is actually doing something in this report, its definately not curing everything and getting rid of all the plaque, but its reducing it somewhat, this is a very positive sign to me. A pessimist would point out that the first study done by auxillium only had a 53% success rate at the six month post last injection mark. However this study only did 2 series of three injections, when the series was bumped up to 3 series it seems as if better success and improvment was achieved, could this be a coincidence, it could be, more studies would solidify this second study done by Auxillium and I'm guessing in phase III we will see more than 9 patients per study, and more mixing and matching of 2 series and 3 series of injections? Is there anything else they will add in the next phase of trials? Will they report what % in reduction of curve is achieved for those achieving more than 25%? I think we should all stay positive with this, it appears that collaganese does indeed work, I remember someone somewhere, perhaps it was on the old BTC forum saying Dr. Martin Gelbard had tried collaganese injections in the 1980's and they were a failure, this made me wonder why someone else would pursue testing collaganese injections, it appears that poster was wrong.
ComeBackid
Quote from: Rico on October 29, 2006, 06:50:32 PM
Gerald Jordan report was a "Investor Relation piece" prior to third quarter earnings, nothing more or less...
Rico by this do you mean that Dr. Jordan wrote his piece in a bias way to sway potential investors? Does Dr. Jordan get a kickback from this company or have a stake in this company? If he is a cutter like some say, this being a success wouldn't be in his best financial interest. If you are saying he wrote his piece in a bias way, even if he did do that, what evidence do we have that he did, it would seem to me that all we might have would be speculation, therefore we can't claim this honestly. I guess with the culture of corruption that we live in today, it leaves many of us thinking twice and being skeptics.
ComeBackid
Hopefully I am not on a different planet as I jump in here, but I believe that what is being discussed is Collagenase (of Biospecifics fame). Correct me if I am wrong. So assuming that I am on topic and not out to lunch as I jump into this torrid discussion, I would have to say that my concerns about Collagenase are not really to question its effectiveness. I think that its short term effectiveness is becoming more and more apparent and it *finally* looks like it might make it to a doctor's office near you and I. Rather, my concern has more to do with whether this will prove to be a lasting solution to the problem. For Peyronies to form in the first place requires that something be dreadfully wrong with the bodies healing process. So the question is, will simply dissolving the plaque prove to be a cure? It requires injections which involve a certain amount of additional trauma. Will this trauma lead to the progressive appearance of new lessions? If it proves to be a definitive treatment that passes the test of time, that will indeed be welcome news. But in the end, it may prove to be a multistep process involving dissolving the plaque much like one would excise a tumor, and then using Pentox or some other treatment to prevent a recurrence. I am not sure that enough time has passed with the trials to know whether this cure can stick on its own or whether it will need some help. But I am sure that it will be very beneficial to control inflammation during and following treatment, and that failing to do so could only encourage a recurrence. Those are my thoughts. But other than that, I am delighted that yet another potential NON-SURGICAL cure is on the horizon. That is good news.
- George
Forum members and guests:
I had posted several post on AA4500, I deleted them....I will leave this up to the medical community and test of time.....
Hawk on inflammation and reduction of curve....once the inflammation settles down so might the condition or result of it...I know this to be the case with injuries...also with my own peyronies....acute or chronic inflammation.....the window or six months to a year seems to be the natural course of the disease....If one was to ease up on his inflammation or become stable, then maybe he could have a reduction in curve, say like 25%....I have read many post where a man went from 60 to 45 degrees.... Maybe Tim could jump in here....he has a gift of putting it in perspective...
Rico
Sinply put, Peyronies Disease is - at least - an inflammatory disease. In some situations it may be more akin to a "normal" healing reaction to trauma. For instance with a "penile fracture" or a similar injury, the development of a scar might be considered "normal". But for many of us, it seems to be an *inflammatory* reaction to microscopic injuries of which we are not even aware. The definition of inflammation has to do with the presence in the placque of certain kinds of white cells and inflammtory mediators.
To the extent that *any* anti-inflammatory therapy "works", then it makes sense that reducing inflammation in the active place will make the curvature better. Indeed, that would be a fairly good hypothesis for how or why Pentox works.
I completely agree with George that this may prove to be only half a solution. Like surgery, this is geared at fixing the problem, but does not say much to the matter of staying fixed. Many of us have experienced multiple bouts of worsening. Many of us have read of therapies that fail down the road.
Ultimately, this may prove to be a good way to get better faster - to "debulk" the lesion in a sense. Then it will be left to altering the basic inflammatory pathways that promote such lesions to prevent a recurrence. Similarly, I think that the VED will prove to be a VERY important part of prevention in the future.
Tim
Quote from: Rico on October 30, 2006, 12:49:19 AM
Hawk on inflammation and reduction of curve....once the inflammation settles down so might the condition or result of it...I know this to be the case with injuries...also with my own peyronies....acute or chronic inflammation.....the window or six months to a year seems to be the natural course of the disease....If one was to ease up on his inflammation or become stable, then maybe he could have a reduction in curve, say like 25%....I have read many post where a man went from 60 to 45 degrees....
Rico,
You offer only a statement that Peyronies Disease inflammation always gets better, at least for periods of time, and that degree of curve often improves somewhat. It offers no evidence that the improvement is not from an increase in elasticity on the short side of the curve.
Physical science and geometry make it clear that:
Every curved object is shorter on the inside of the curve than on the outside of that curve.
Straightening that curve means lengthening the short side or shortening the long side.
Short of surgery, lengthening the short side can only be done by elasticity (stretching cells without increasing numbers) or adding to the numbers of cells aligned on the short side. In fact it is done that way with surgery by adding cells or a scaffold for them to grow on with a graft.
I do not believe just reducing inflammation in cells on the short side (where the scar is) can make that side longer since it does neither of the above. It may allow normalization to take place that allows the cells to gradually grow into a more elastic structure, but that is elasticity reducing the curve not reduction in inflammation. You are the only one I have ever heard say reducing inflammation reduces the curve and you offer absolutely no explanation that can be considered in order to convince anyone.. Your explanation above offers several statements, but none of them have anything to do with your conclusion that reducing the inflammation will reduce penile deformity without increasing elasticity.
Just saying it again does not explain it or make it so.
Hawk,
I always said I was coachable:)....and if you do read my quote you posted, it says, might...could...maybe....seems.... I put no absolute in my statement..... I understand what you are saying, but the area that surrounds the plaque can be inflammed...the outer edge of the scar area....this tissue will become painful and less mobile also, hence the larger the wound seems and more swelling, once it subsides it becomes more natural as the scar develops....also this outer edge can be the weakest spot in the chain....this is why one has to be careful with the VED....
Is there a Doctor in the HOUSE!!....Tim please jump in....
Rico
Rico
Rico, I did jump in!
Hawk, such concepts are not mutually exclusive. Reducing inflammation would seem to be key to "healing" from a problem that seems to be inflammatory in nature. Without healing, the ongoing inflammation would seem to promote laying down of collagen and fibrin and promoting scarification. OTOH, reducing it would allow for a reduction in the inflammatory triggers, that in turn allow natural healing to improve the situation (meaning that collagen is eaten up by natural collegenases, and remodeling occurs.
Elasticity is perhaps not the right term. I think of that as meaning the stretchability of a tissue. At tension (fully erect), the tunica albuginea does not "stretch" any further. VED proponents argue that over a long time of stretching one can make a penis bigger, but the general concensus is that it does not really stretch. Rather, it is stretched to a pre-determined set point, and then it is quite taut.
It is the loss of normal tissue that prevents it from stretching out to the predetermined length. It is more akin to the curved side of the penis having a "tuck" taken in, such that when erect, and again taut, the TA is simply shorter. So I think of this as replacing scarred and contracted tissue with normal TA as the goal of therapy.
The VED may work simply by stretching out the scar tissue, or it may stimulate remodeling. Data from skin stretched out with tissue expanders suggests that it is simply a stretching of what is there, instead of any sort of remodeling (which would entail cell/cell signaling to make new cells; that is the mechanism for new tissue formation in other areas of research - but not skin).
At any rate, thinking that reducing inflammation would be of value in Peyronies Disease is not new or novel. It is why we have taken things like POTABA, vitamin E, Pentox and Advil.
Tim
Tim,
Such an accepted concept as the value of reducing inflammation has never been at question. Nor, has it ever been implied that one process excludes the other.
My point was simply that Rico responded to my post which stated that deformity is related to elasticity, by saying that this was not the only way "also the reduction of inflammation reduces curve" I am very aware of studies and research on stretching dermal tissue in burn patients and the discussion of "stretching existing cells Vs. generating additional cells"
My point is cross linked scar tissue does not expand like "elastic TA" Just removing inflammation alone does not also change deformity.
Hawk,
Do you think that swelling might cause one to be deformed, a swollen ankle, it is full of inflammation, once the inflammation subsides so might the swelling, which makes it deformed.... there could be several reasons for deformation ..and the action of therapy seems to go along that way also, to attack the inflammation, and then to remold the plaque and supply your unit with oxygen rich blood and the extra Punch with pde5 inhibitors..... my input on elastic tissue was that the bend can be influence also by the stages of inflammation that go along with peyronies, and as Tim said, this is nothing new....
Rico
Rico,
I do not think SWELLING on the short side (where the plaque is) would make the short side shorter. If anything it would fill that area and reduce the curve.
BTW: Normal disease progression on Peyronies Disease is that plaque nodules often reduce in size after the inflammatory phase and the curve and ED becomes worse during this process. Probably due to contracture of plaque tissue (my guess). Often men take the reduction in plaque size as a sign some treatment is working even though this is classic progression and the curve is not improving. So, often the reduction in inflammation is accompanied by a reduction in pain but added deformity. I believe Dr. Mulhall wrote on this topic.
I may move these posts to the "Disease Progression" topic to clean this thread up.
Hawk you raise a good point here on the inflammation going away and the healing of the peyronies plaque. As my plaque healed the scar tissue contracted, causing ED and more deformity and bend in my penis. So in one sense the pain and inflammation went away as my penis "healed," yet my peyronies really got worse to me. A lot of people talk about reducing the plaque, however this may not be desired, if half of ones tunica has turned to plaque and you then reduce that plaque, you are reducing size as well, so your healing plaque but losing size. The most desired result would be to dissolve the plaque and have new cells regrow or regenerate. Or to stretch the plaque out with a VED to regain size and just let it in there, because if one reduces the plaque they will lose size instead of keeping the plaque and stretching it out. It appears that AA4500 must dissolve the plaque, not simply reduce it, because if the plaque was being shrunken down, you wouldn't see a gain in size or a loss in curve necessarily.
Just to let you all know my own experience which I am VERY familiar with. The INITIAL inflammatory stage for me was VERY painful. But it caused no loss in size, in fact I distinctly remember an odd gain in size during time I was very inflammed. But let me tell you, when the pain relented, everything got smaller quickly. As far as new inflammatory cycles go, or going in and out of the 'active phase', I would suggest that the shrinkage involved is due to new plaque CAUSED by the inflamation and not by the inflammation itself. At this point it is clear that Collagenase dissolves the plaque in such a way that it preserves and 'unlocks' the underlying tissue so that it once again can have its normal elastic characteristics. As I have said before, whether or not this 'cure' will stand the test of time is yet to be seen, but what is very clear is that this treatment is addressing a whole lot more than just inflammation. Granted, the removal of the plaque will have the effect of reducing inflammation that that plaque tends to generate, but the complete picture is a whole lot larger than inflammation. Having said that, I really do welcome the coming of Collagenase and expect that it will be a useful treatment for Peyronies even if it needs a little help along the way.
- George
The initial engineering batch of AA4500 has been produced at Auxilium's new Pennsylvania facility. They also announced today that Phase III AA4500 trials for Dupuytren's Contracture are to begin early Nov 06 with about 200 patients at 15 sites. Outside of plaque studies were not required by the FDA prior to this study. It is to be a double blind placebo trial. Placebo patients will be offered the opportunity to receive AA4500 injections after the study is complete. There will be trials in U.S. & Europe. They are not releasing the names of the European countries as yet. Future 07 tests, possibly mid year, are to be open label. They state that AA4500's orphan drug designation does not guarantee FDA fast track approval after BLA submission. As for AA4500 Phase IIb trials in 07 for peyronie's, they are considering a protocol of more evenly spaced injections with an overall much shorter timeframe than in Phase II. Source: webcast of Q&A with institutional investors.
Mark,
Thanks for the update, so it appears that these Phase IIb peyronies trials will start sometime in 07, as a general rule of thumb I'd say later than sooner into the year. So the real quetion is how soon will someone be able to recieve an injection from their doctor? If the studies go well for the dupuytrens and there is quick approval that should be good for us. I"m hoping they will add much more detail in their next batch of peyronies studies. I'm still a bit perplexed why they didn't measure the % reduction of curve in each patient in their last study, especially when they only have 9 patients in one of them.
Mark,
To me it would seem that if they did the know the % reduction in curve of each patient, and that % was significantly higher or generally higher than 25%, it would seem to me that it would be in the best interest of Auxillium to get that information published and recorded in the final analysis. It would also seem that a Dr. would want to be as thorough as possible in his report and analysis. I'm going to be pretty frank, the vagueness of this report is quite concerning, however I don't question the integrity of this report, I do question the vagueness. Why wouldn't a company want to report the facts on a test as best as possible, especially if they were good results? Something doesn't seem right with that aspect. Hopefully Dr. Jordan just did a vague report and there isn't anything fishy going on, and hopefully the next set of trials will have more detailed reports. I think we all have our fingers crossed and are hoping for the best from Auxllium. I'm betting at least a couple of people on this forum get involved in the next set of trials, I know gary from Auxillium was taking names for anyone interested.
ComeBackid
ComeBackid:
I don't know if you read the investor report, but I pasted an excerpt below. It would appear to me that the detail in the statement is about right for an investor report. All in all I think this shows real promise.
Another bit of interesting info at "www.auxilium.com" is an Adobe file "November '06 Presentation". Pages 25 through 28 are of particular interest. Again, I like what I read except for the 2009 market date and two glaring errors. They grossly underestimate the number of Peyronies Disease patients (but still feel the numbers are a good profit base), and state that the disease affects mainly those over 50 years of age. Click "Investor Relations" and then "Presentations" to get the file.
Larry
In Study A (n=25), 3 injections of AA4500, each administered on a separate day, were given over 7-10 days. Patients received a second series of 3 injections 12 weeks later. Patients were evaluated at three, six, and nine months post-last injection. The mean baseline deviation angle was 52.8 degrees. At months three and six, 58 percent and 53 percent of patients (respectively) achieved clinical success with respect to deviation angle.
The best results were achieved with a three-treatment series of three injections each in Study B (n=10). In Study B, patients received three injections of AA4500 administered one per day, separated by at least one day each, over a one week timeframe. Patients received two additional series of 3 injections, each spaced 6 weeks apart. The mean baseline deviation angle was 50.2 degrees. At 9 month follow up (post-first injections), 25 percent or greater reduction in deviation angle was achieved in 8/9 patients who completed the study (89 percent, 1 patient had 24 percent reduction in deviation angle). Based on the investigator's global assessment, 67 percent of subjects were very much improved or much improved after treatment with AA4500.
The most common adverse events reported in both studies were local administration site reactions that were mild or moderate in severity, non- serious, and resolved in time without medical attention.
Larry,
OUCH! That photo in the pdf of the surgical treatment wasn't pretty...and I thought the shots were bad! I'm assuming that the little blue cord is holding up the nerve bundle?
Everytime I see a picture like this, I keep pushing the surgical option further and further back on my list! I wonder if I can wait until 2009, or maybe get signed up for one of the studies ::)?
Steve
Steve:
Yeah, I know what you mean, I have a paper on the surgical approach published several years ago with several photos like the one in the presentation. However, they were not in living color like this one. It appears the penis is still de-gloved so it looks especially bad, but on the other hand it is straight, and the before photo is a real mess.
I had an appointment scheduled with Dr. Jordan about 9 months ago and had to cancel. I sure wish I had been able to keep it as I may have been in the study.
Larry
Words may have meaning but choice of terminology still has impact. For instance:
degloved Vs. skinned or scalped
More direct link http://library.corporate-ir.net/library/14/142/142125/items/219113/AUXLNovember2006.pdf
Hawk:
I'm not real bright and you are making me guess what you are getting at, so let me have it in plane speak.
Larry
Larry,
It was just wise crack commenting on how nice the term degloved sounds for such an ugly procedure. I am sure surgeons no doubt coined that term to prevent having to say, "Mr. Holcombe, we will then skin your penis like a dead muskrat. When would you like to schedule this procedure?" :)
A rose by any other name is still a rose, and if that ain't skinning then I never skinned an animal (and I have).
Maybe if they came up with a neat sounding name for castration, we would all sign up :)
Hawk:
Growing up on a farm in a very rural area, when we castrated our animals, we simply said, "Time to 'cut' all the male pigs and calves".
Guess the term "cut" would turn off the pleasure, huh?
Old Man
I was thinking of something nicer sounding like a testicular redistribution
Larry,
I did read the report, I don't know much about investor presentations or reports, so I'll take your word on the vagueness. I know some others besides me have expressed concern on the vagueness of the report, time will tell especially when the next phase of trials takes place. Kobold and I talked in depth about the company, we believe their investor pipeline is strong, and the investors believe in the company, there product should be successful and it is my belief they will become a very profitable company in the future.
ComeBackid
Hawk:
That's what I thought you were getting at as some medical terms can be .....uh, amusing. It would seem that saying the skin is retracted would work better, but perhaps some things need to be in code especially when it involves cutting on your manhood.
ComeBackid:
I really think they went into all the detail necessary for a investor relations report. What would be interesting would be securing the report that Dr. Jordan made to the AUA in Maui.
Another thought comes to mind on the figures used by Auxilium as to the incidence of the disease. They may believe that it is far higher than they state, but it may be better to encourage or promote orphan status for the disease. Without going back and making a review of orphan status I believe it allows the FDA to grant flexability in drug development and studies, as well as some positive financial incentives.
Larry
Try a Pub Med search on perfenidone. I remember seeing studies. They were not impressive to me at the time. I have kinda dumped it in my failed Peyronies Disease treatment dumpster (started with a garbage can and had to go much larger) and forgot it. Maybe you can find something new about it
There are ongoing multi-center trials of perfenidone, which inhibits TGF-Beta1 much like Pentox does, for idiopathic pulmonary fibrosis (IPF). Although it occured to me that it might be of value for Peyronies Disease, I know of no data showing that (or that it helps Dupuytren's either).
It makes sense that it would help, but the data seem to show only a partial improvement in IPF. I believe that such drugs will play a role in modifying or treating Peyronies Disease, but we are not there yet - and it's frustrating.
Tim
Some thoughts on the Auxilium studies:
25 percent may sound substantial until you consider that a patient receiving AA4500 who began with a curve of, say, 80-90 degrees, will still end up at no better than 60-65 degrees. Those beginning with curvature of 40 can only hope to reduce that to 30. Some guys already see that amount of "improvement" with other treatments that are now viewed as marginal, or even after no treatment at all.
The report makes no mention of how early in the course of the disease the treatment was applied or how much calcification was believed to be already present. If the studies involved new active-phase patients, the results obtained would be even less impressive (or, conversely, more impressive if it involved longer-term patients.)
Efficacy in the long run is most critical for any treatment that seems directed at removing a symptom, but not eliminating the cause. It will take quite some time for the research to show, if it ever will, that men who are prone to spontaneous scarring of the tunica will suddenly and permanently cease to have that tendency after treatment to dissolve the plaque they already have. Those who can't account for how their own disease process started have always been unsure about what they can do differently to prevent worsening or recurrences. Those same patients will also have doubts about whether AA4500 will do anything more than clear away a portion of what may simply continue as an ongoing build-up.
By the way, there is no error in those old posts which say that Collegease was indeed experimented with by Dr. Gelbard in the 1980's. The patent application from the university involved can be viewed online and is clear about the dates, the researchers and the fact that they used a collegenase (which type, I don't recall though, and I wouldn't understand the difference.) If it was proven very beneficial at that time, it would not have taken 20 years for the treatment to be revived.
Kevin,
I share your same concerns about the fact that according to this study, one with a curve of 80-90 degrees will only reduce their curve to 60-65 degrees after treatment. I also questioned the vagueness of the report, and lack of specific details about such things as size measurements, and what the % reduction in curve was for those who saw a greater than 25% reduction in curve. However, I think it is good news that the treatments are doing something, meaning they are working at least a little. I think it is fair to say that Auxillium is still tweaking the dosages, so more powerful concentrations may show more improvment. It is clear that we can't form a final judgement on these early results, and more clinical trials will be necessary. I don't know much about investor reports, but Larry pointed out that the amount of detail in this investor relation report was considered normal, so perhaps Dr. Jordan knows more than he is telling us in his report.
FYI, the interest in Perfenidone began with this posting on the BSTC forum in 2004. I've followed that forum for almost 10 years now and this is, in my opinion, the single credible report of a drug having a positive effect on Dupuytren's.
Date: 3/15/2004 2:28:14 PM
Subject: Pirfenidone
Name: George
Email: gtyson@hyperioninc.cm
I was diagnosed with Dupuytrens about 10 years ago and had a very successful palmar fasciectomy about 7 years ago. Nonetheless, the nodules and bands continued to develop in other parts of both hands. Two years ago, I started treatment in a clinical study of an investigational drug, pirfenidone - an anti-fibrotic which has been successful in treating pulmonary fibrosis. The purpose of my study was to investigate the drug for treatment of radiation-induced fibrosis. (I was treated with radiation and chemotherapy six years ago for throat cancer). The drug helped a lot with my swallowing but I also noted a distinct improvement in the Dupuytrens. It used to be painful for me to tightly grasp certain objects - no more. I saw my hand surgeon last week and he measured my range of motion in all fingers as at or within 2% of normal. On some fingers, the bands have disappeared and on others, they have significantly reduced. So, something is going on and I think it is the pirfenidone.
There were less than 10 people in my study and there are not that many people with pulmonary fibrosis so I might be the only person taking this drug who happened to also have Dupuytrens.
I have emailed the manufacturer of the drug to make sure that they know about my experience. I am not sure what to do next but I would like to get some organization to press the manufacturer to conduct a study of this drug on DC victims. BTW, the only side effect I experienced was some stomach upset which Prilosec counteracted and some fatigue during the first few months of the study
As I mentioned to ComeBackid, the report on the study was written by Auxilium and not by Dr. Jordan. It was directed at investors who only need to know the bottom line, not patients who want to know specifics. It was condensed from a report given by Dr. Jordan to an AUA meeting in Hawaii. If someone has a copy of the abstract by Dr. Jordan and feels that it is vague, that's one thing, but to continue harp on the vagueness of this investor report is foolish.
As I read the report it states that in study B, 8 of 9 patients had a 25% OR GREATER reduction in bend. I don't know about the rest of you, but I would be delighted with a 25% improvement. Now, the study is not conclusive but it does show promise as a possible treatment. A statement was made that some patients see that type of improvement with other treatments. Perhaps, but I've been involved in Peyronies Disease advocacy now for seven years and I don't know of any treatments that have prov-en to be of benefit. I personally had 12 treatments of intralesional verapamil several years ago only to have my condition worsen. I've taken vitamin E, Potaba, Colchicine, and used a VED. The VED is the only thing that has shown some possible slight improvement, but nothing near 25%.
I think these discussions sometimes miss the point. When we talk about treating the disease we are talking about one thing, when we talk of curing the disease we are talking about something else. I have coronary artery disease and have had angioplasty and placement of a stent. This is not a cure for my disease but a treatment to reduce or eliminate angina pain and stress on my heart. I don't think it has been suggested that AA4500 will cure Peyronie's, but it is being studied as a treatment for the conditions resulting from the disease. Many diseases are not really curable. I can't cure my heart disease but I can treat it and control the advancement to some extent. The same is true for other diseases like arthritis. Also, some people are predisposed to one disease or another. It's my belief that the same is true for Peyronie's. When we learn the cause, and there are probably several, it's probable that we will also learn that we can't cure it, but we will at some point be able to successfully treat the symptoms.
As far as Martin Gelbard being involved in a study 20 years ago, one only needs to look at the history of AA4500 with BioSpecifics and Auxilium to see that even if he saw positive results it's reasonable to see how the development could flounder for that many years.
I take the time to go into this because I think that rather than discussing Auxilium and the development of AA4500 in the negative, we should be supporting and encourageing them to press on with the development of the drug with all due speed. Go to their web site and send them an Email. Let them know you are out here and will use their drug if proven successful, I have. It's a positive step that takes little effort with no downside.
Larry
Well stated Larry, Well stated!
Thanks for posting that. Timely indeed. Curtailing the bashing of AA4500 is certainly welcomed in my book.
Power
Perfenidone and Pentox both work by inhibiting the actions of TGF Beta-1. TGF is a pro-inflammatory cytokine that mediates a lot of it's effects through arginase to collagen and proline/urea cycle.
I just read an interesting article or two about "genetic modifiers" in cystic fibrosis (CF). Interestingly, patients with CF, who share identical genetic mutations causing their disease, have a great deal of diversity in how sick they are. Now, so-called "genetic modifiers" are being identified that might make them better or worse. And, equally interesting, those who over express TGF-Beta-1 get sicker than those who do not.
So in this condition (CF), where there is a constant inflammatory trigger in the body, those who make too much TGF do worse. It turns out that there is a "codon" that promotes higher production of TGF in those individuals, and it's genetic locus has been identified.
Here is the stimulting part to me. Recently (last week) a team of doctors scanned the ENTIRE genome of a lot of patients with Crohns disease to look for modifiers. There is a new technology that allows this kind of fishing expedition called a DNA chip that allows one to look quickly at all single nucleotide polymorphisms (SNP's) (mutations) for an enormous number of sites (all of the genes!!). This then identified modifiers of Crohn's disease (specifically looking at interleukin023 and up and down regulators of it).
So it would be possible to draw blood on any man (how about ALL men) with Peyronies Disease, and to run a similar scan. It ocld identify all potential denetic modifiers of this disease and help us understand what promotes it and what might prevent it! And if we had blood from over 1-2,000 men, we could do it within 2-4 weeks.
All we need is a cracker-jack researcher in this field, and unfortunately we ain't got many of those.
Tim
Tim,
Sign me up! Here's my blood ♥.
Where can we find some Grad Students willing to take on this project? Looks like a good subject for a thesis?
Tim, what is also interesting to me is that when you start to review research on kidney failure, you discover that one of the primary bad guys that has been identified there is also TGF-beta. In fact Pentox has been actually suggested in the treatment of kidney failure and the thought among some researchers is that if enough of these pathways can be identified and blocked, it might even be possible to reverse kidney failure. In fact right now there are researchers attempting to identify a possible 'point of no return' so that they don't waste time with people who are too advanced to benefit from possible therapies. But I think I recall reading of another powerful TGF-beta inhibitor in relation to that research, I don't recall what it was, but if I come across it, I will add it to this post.
And to all who might not be aware: It is important also to understand that TGF-beta itself is not 'bad', it fulfills an essential function it the body. It is only when it gets out of balance that it becomes a problem and the purpose of inhibiting it is not to eliminate its function completely, but rather to attempt a 'correction' in its effects in order to restore balance. Some folks read 'inhibit' to mean block 100%. In reality when we talk of 'inhibit' or 'block' in medical terms, it means to in effect 'throttle back' if you will rather than complete inhibition, in which case the cure might prove far more deadly than the disease.- George
Well, I found some more info. The TGF-beta inhibitor being investigated for kidney disease is something called BMP-7. Here's the quote:
QuoteThe actions of BMP-7 in chronic kidney disease involve inhibiting TGF-beta stimulated processes
And here's the link to this very interesting presentation: http://www.ndt-educational.org/hruskaslide.asp (http://www.ndt-educational.org/hruskaslide.asp)
Be sure not to miss the section on the effect of BMP-7 on calcification!
Thanks for the hot tip George.
BMP-7 is a natural inhibitor of TGFBeta effects - and when one does not make enough of it, then TGF goes forward uninhibited and unchecked, and this leads to the damage. A similar issue is seen in Peyronies Disease:
"The ability of both TA and Peyronies Disease cells to induce a typical osteogenic differentiation of the target mesenchymal multipotent cell line C3H10T(1/2),... may be due to the secretion of osteogenic factors such as BMP2 or some other BMP, like BMP4 ... some of which we found were upregulated in the Peyronies Disease cells..."
(from "Evidence That Osteogenic Progenitor Cells in the Human Tunica Albuginea May Originate from Stem Cells: Implications for Peyronie Disease")
http://www.bioone.org/perlserv/?request=get-document&issn=0006-3363&volume=073&issue=06&page=1199
So there is emerging evidence that the inflammatory pathways which affect our lives so very much, comes from a dysregulation of these critical pathways of wound healing gone awry. The BMP's are called a "sub-family" of the "TGF super-family" of proteins - a concept I have to work harder to understand!
Tim
I believe as we speak of the AA4500 and all Bmp-7 or all these underlying health issues...the cure or huge help with this is with the new fde5 inhibitors.... this is the designer drug ciliais.... as the baby boomers fuel this billion dollar industry, they will get better and they will deliver oxygen rich blood and produce phostaslandine E1 and activate the enzyme which suppresses collagen.... at least to be the piece of the puzzle that keeps it at bay once the plaque is removed, if this doesn't do it, maybe the aa4500 will, and the ved will remold the unit and the maintance will be the new fde5 drugs which are being developed as we speak....I'm 100% sure that these drugs will play a huge part in finding the cure or assisting in the future with the program....there is hope, Baby Boomer Power, 30% of population, 50% GNP.....powerful!!!!!!!!
Rico
I am close to one of the top fundraisers for CF in Miami- I want to learn more about the drug- who is the manufacturer?- Can you let me know?
Thanks,
Hopeful
Quote from: j on November 09, 2006, 10:05:42 AM
FYI, the interest in Perfenidone began with this posting on the BSTC forum in 2004. I've followed that forum for almost 10 years now and this is, in my opinion, the single credible report of a drug having a positive effect on Dupuytren's.
Auxilium called me twice today. First they left a message and then called back to talk to me personally. They wanted to give me a heads up on the Dupuytrens study in Atlanta. I gave them my name a couple of months ago to get on a list for Peyronies Disease and Dupuytrens.
Just wanted to let everyone know they were good to their word. BTW, I am not going to participate because of the time involvement and distance. I told him I would go for any Peyronies Disease trials without hesitation. He assured me I would be notified.
Just a ray of hope :).
Liam
One drug that seems quite promising from the literature is Liposomal recombinant human superoxide dismutase (lrhSOD). There's an article describing the results from testing (double-blind,placebo controlled), the abstract can be found at:
http://cat.inist.fr/?aModele=afficheN&cpsidt=17107779
I actually emailed the company, Polymun Scientific (http://www.polymun.com/), in Vienna, Austria, about this drug which they call Lipoxysan. They said they're a small biotech company and they have not been able to find anyone to commercialize it.
Anyone out there have any connections with the major pharmaceuticals? Given their results, it seems like a no-brainer that this could help a large number of people out there. Do the pharmaceuticals not want to license it because there might be something better coming down the pike? Are the profits just not there?
Here's the abstract of their study:
Résumé / Abstract
Objective: To demonstrate the efficacy and safety of a topical gel containing liposomally encapsulated recombinant human Superoxide Dismutase (lrhSOD) in the treatment of painful Peyronie's Disease. The theoretical background is that lrhSOD, by scavenging of free oxygen radicals, might interrupt inflammatory cascades and thereby limit further disease progression. Methods: In a placebo-controlled randomized clinical trial, 39 patients with Peyronie's Disease and significant pain symptoms were treated with lrhSOD or placebo for a 4 week period. At this time, statistical evaluation of pain resolution was performed as primary study endpoint. Patients then were continued in a cross-over study design to ensure a total of 8 weeks of lrhSOD therapy for all study participants. Pain, plaque and curvature assessment was performed at study entry and every 4 weeks until week 12. Results: LrhSOD treatment resulted in a statistically significant reduction of pain (p = 0.017) compared to placebo already after 4 weeks. At week 12 pain was significantly reduced in 89% of patients who all had received 8 weeks of lrhSOD therapy at that time. Response to other disease parameters was assessed at week 12: plaque size was reduced in 47% of patients, as was plaque consistence in 38%. Penile curvature was improved at 5-30 degrees in 23% of patients. The expected spontaneous disease progression rate of up to 40%, as reported by several investigators, was significantly reduced to < 10% under lrhSOD therapy, and patients satisfaction was high, also consequent to the lack of therapy-related side effects observed in the present study. Conclusion: LrhSOD is an easily administrable, safe and effective local therapeutic for the painful phase of Peyronie's Disease.
Revue / Journal Title
European urology (Eur. urol.) ISSN 0302-2838 CODEN EUURAV
SMS(sexual medicine society) had it's fall meeting November 2-5, 2006 in Las Vegas... Dr. Tom Lue heads up the society and Dr. Levine and many other top Urologist where there..... I downloaded a itinerary looking if peyronies was on the table for discussion.... they have many break out sessions on the table, and when the dick doctors aren't at the other tables throwing the bones(playing craps:)), they go to the ones of there choice...
There was one on operation and a couple of others on peyronies, nothing on VED that I saw, one on upping the dose from 10 to 20 on the injections...
Lots of break out sessions on cialias and its effect of scar tissue ect....found this intersting, and also on the effects of taking daily...
Peyronies was in four different sessions...one with cutting, one with injections, one on coping and demographic studies....
I can't help but seeing a bunch of dick doctors partying in Vegas, pockets stuff with Viagra or cialis....what happens in Vegas stays in Vegas ;D!
Maybe the report will be available soon in urotoday.....seems anti fibroid and cialias is a hot topic...
Rico..........
JW, what you are describing appears for all the world to be a topical anti-oxidant. That would be very interesting, since it demonstrates the power of antioxidants against Peyronies to the point of being capable of even reversing the disease. It also reinforces the concept of taking large doses of anti-oxidant supplements. But this is indeed an interesting product with a delivery system that appears to work OK transdermally. To bad that it faces a million dollar barrier in terms of drug trials to achieve FDA approval in the US. I find that whole system disgusting.
- George
There is a spray S.O.D. available that is for hair loss, wrinkles, skin healing, etc. Do you think there is anyway that it could penetrate into the penis and go after the plaque? I know it sounds crazy, but anything is possible I guess. Maybe I'm asking for too much here. Thoughts? crs
JW
Somewhere on this site I saw a reference to superoxide dismutase - in UroToday - European Urolgy 2006. It said:
Quote'Superoxide dismutase No placebo-controlled study No longer relevant, withdrawn from market'
There still may be something in it though.
Regards,
Percival
Percival,
Yup, it was my understanding that there was a similar product based on animal tissue (the original superoxide dismutase), but some people had bad allergies to that, and so it was withdrawn from the market. The lrhSOD is based on human DNA and so my (minimal) understanding of the theory is that it would not cause the allergic reactions associated with the original. That's also in a European Urology survey article.
JW
--------------------------------------------------------------
JW
Somewhere on this site I saw a reference to superoxide dismutase - in UroToday - European Urolgy 2006. It said:
Quote
'Superoxide dismutase No placebo-controlled study No longer relevant, withdrawn from market'
There still may be something in it though.
Regards,
Percival
Auxilium announced today that phase III trials of AA4500 use for Dupuytren's have begun in Australia and Switzerland.
Hey Guys,
Looks like AA4500 it making progress. Check out the link below:
http://phoenix.corporate-ir.net/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=933100&highlight=
Keep fighting the good fight.
Power
I don't mean to rain on the parade. I think and hope that AA4500 will represent some advance in treatment over Verapamil injections and other treatments. It does appear however that the best case scenario is that AA4500 will reduce major plaque formations in concentrated areas of the tunica. I think those with limited curvature and general loss of size from generalized plaque, and even those with hourglass deformity will gain little even if the drug wins FDA approval.
Hey Hawk (and others),
May I ask what you think AA4500 will be able to accomplish should it be given FDA approval?
Power
As stated:
Quote from: Hawk on November 20, 2006, 03:49:11 PM
AA4500 will reduce major concentrations of plaque formations on the tunica.
I am thinking that what you stated concerning AA4500 would at least help in erection qualities for those suffering with ED.
IMHO that is a pretty good benefit in the real perspective.
We will sooner or later see what happens with this drug. I will continue to hope in its efficacy to do anything to help peyronies sufferers.
Power
I agree it would be a significant improvement for many
I just got back from the first visit to my urologist in over a year and I thought I would share the good experience and my hopefulness with you all. I brought in photocopies of the research on P, L-A, &C that I had mostly been directed to on this board. In addition I brought in Dr. Lue's list of publications and PDR references on Pentox. My urologist, who had to date done nothing for me but suggest Vitamin E, was very pleased to see this research (made copies for himself) and even thanked me for teaching him something! He then wrote the prescriptions for me (Pentox and Cialis) in three month scripts and asked me to keep in touch about results. (I am very glad I have good prescription coverage)
I don't honestly believe I will see much if any improvement in my condition, since my main issue is shrinkage and an hourglass deformity. But I am very hopeful that this may prevent further acute phases and any further decline. I'll keep a journal and report in after 3 months.
Thank you all for help and advice!
---PJ
PJ,
That is encouraging that your doctor was open to information. I would say he is a keeper.
When you return, or if so inclined to make a special drop by visit, it would be nice if you would consider directing him to www.PeyroniesSociety.org and tell him to click on the forum button to check out the our forum.
Keep us posted. I am very interested in your results
Hawk
Hawk,
I did mention the forum to him. He seemed interested only in that I was "corresponding" with patients of other urologists. He stated that he felt that was a very positive thing for me to do and while the research was clearly the deciding factor, he did listen when I talked about things I had learned on the board. I may not understand the medicine angle too well (I lack the background education) but being a psychologist I do know how to discuss research abstracts, so that helps.
The board's url was on the folder I gave him, and I shall directly discuss a board visit when I see him next. If he did come by the forum I am sure he would recognize our latest visit's description from my post but could not id himself as my DR due to HIPAA regulations.
When my next Dr visit is will depend on his comfort with prescribing refills and whether or not my insurance covers the visit. Not to get too off topic (and I am not looking for conversation on the topic of insurance since it has no bearing on anyone else's situation) my insurance does not cover visits for Peyronies, so they run me about $300 a piece. This visit was coded ED since that was a legitimate conversation in the Dr visit and will likely be covered.
---PJ
Everyone,
I am a person that had Peyronie's Disease in 1990 and no longer have it. It lasted for about 1 yr. It was very painful and to tell the truth I had not thought much about it until today when I happened to mention it in a conversation with a friend. I wanted to post here to let everyone know what actually worked for me back in 1990 as far as treatment. The doctor put me on Potaba for 1 yr and at the end of the end the last scar to disappear was actually the first one to appear. In total I had 5 scars that all connected. I will say that the only lasting effect of the disease is the size of my penis was about 1 inch shorter and not as thick. It still does curve back towards my belly which it never did before but not as bad as when I had the disease so it is not an issue. The good news is I have never had anymore issues all these years and no problems with ED. I am currently 47 yrs old and this happened in 1990 when I was 31. Just thought you guys might want to hear a success story. I will bookmark this forum and check back at times to see if anyone has questions. Good luck to everyone. I will never forget the pain I had with this little known disease. CRV
Thanks for the info crv, it's very encouraging to hear from someone who's beat this thing, no matter how he's done it! You might want to hit the 'NOTIFY' tab at the top of the messages in this forum. That way, you'll get an email messag whenever there are new messages on this subject, and you can easily see if someone's asking you a question.
Again, Congratulations ;D
Indeed! I join Steve in welcoming you, crv. This forum has far too few 'alumni' members who have been down the path and found the exit door. Your post is very encouraging and very welcome. We need more guys like you who have found the solution and can encourage the rest of us who are still paddling.
WELCOME!
- George
George,
I am more than glad to help in anyway I can. I can't believe some of the issues that guys are having these days with treatment. I wish everyone a Happy Thanksgiving and heal soon.
CRV
Hawk I'm curious as to how you came to this conclusion:
Quote from: Hawk on November 20, 2006, 03:49:11 PM
It does appear however that the best case scenario is that AA4500 will reduce major plaque formations in concentrated areas of the tunica. I think those with limited curvature and general loss of size from generalized plaque, and even those with hourglass deformity will gain little even if the drug wins FDA approval.
I guess I don't understand how one can come to this conclusion with knowing so little about the drug. To me there are a lot of questions since the report from Dr. Jordan was so vague, we don't know much about just how good the results were and especially there was no part on size gained back. If AA4500 even dissolves plaque a little it shouldn't matter if the plaque is highly concentrated or generalized, it could mean more needle pricks for one with generalized plaque though. I seem to have generalized plaque and hardness all over my penis, perhaps the AA4500 would help improve VED results by making the plaque and tunica more spongy and flexible to stretch. Perhaps AA4500 will be ONE part of a treatment used on peyronies, a new combination perhaps to attack the plaque.
ComeBackid
Hi CRV
Nice to hear a success story. What is interesting is that you got better on POTABA, which many of us feel "doesn't work". Similarly, we have heard here of success with vitamin E, verapamil injections, etc - but none of these things work for everyone - with enough spottiness to the record to make using them seem like a waste of time.
My own experience with POTABA was that it did not work - but I never felt I gave it a fair shake. I found the sheer volume of pills I had to take to be too daunting, and so I simply tapered off of it by "forgetting" until I simply stopped (I was going to say my use "petered out", but that seemed too obvious...). I think my failure to take it was related to my youth (I was 20), and to the minimum effect of the disease on me at that time.
Do you now recall how much and how often you took POTABA?
Tim
Quote from: pudder135 on November 23, 2006, 10:35:45 PM
Hawk I'm curious as to how you came to this conclusion:
Quote from: Hawk on November 20, 2006, 03:49:11 PM
It does appear however that the best case scenario is that AA4500 will reduce major plaque formations in concentrated areas of the tunica. I think those with limited curvature and general loss of size from generalized plaque, and even those with hourglass deformity will gain little even if the drug wins FDA approval.
ComeBackid, I just saw this question:
While we don't know a lot about whether the drug works well on Peyronies Disease, we do know something about the theory of its action an a lot about the delivery system. The delivery seems to be the same delivery system used with injectable verapamil and other injectables used to treat Peyronies Disease.
I am surmising that AA4500 has to be repeatedly put in direct contact with scar tissue to break that scar tissue down. A defined curve caused by a concentration of scar tissue (palpable plaque) would seem a likely target of repeated injections. I do not see how very large areas (up-to the entire tunica) could be targeted. If a penis is uniformly involved, I do not see how it would be possible, or at least practical, to uniformly target the scar tissue. My logic tells me that, if we target the scar tissue in a non-uniform method in such cases, it would cause curvature where none existed.
Tim,
It has been so long since I took the medication I am not sure what the dose what but I think it was 500mg 3 times a day. I am sure that things work differently on everyone but I would give it a chance. Like I said I took it religiously for a entire year. Good Luck!
CRV
Auxilium announced today the temporary suspension of dosing of patients in Phase III trials for Dupuytren's. 27% of material failed the visual appearance test of lyophilized material in some vials of AA4500. It is likely related to higher than expected moisture content within the vial. There have been no reports of adverse reactions. There will be follow up on patients that have received injections in this trial. Investigation is underway to find root cause so that trials can resume. Moisture issue may be cured by extending the lyophilization cycle drying time & modifying manufacturing equipment to obtain lower moisture. Auxilium has requested a review meeting with the FDA to discuss the findings & plans to correct this issue.
After hours trading on the stock took it down 16%....it is down today also, not as bad....it must be a concern or they wouldn't of told the street(stockholders) and having to go to the FDA.... Auxilium doesn't believe it is a containment issue of the drug....let's hope they get there arms around it, all we need is another set back, going to market in a couple of years the way it is....
Rico
I just listen to the Auxilium conference call, not a what you call a warm and fuzzy....the top firms holding stock called in, looking for time frames ect.... a outside firm hired by auxilium spotted the moisture problem...this is reported to the fda, all trials stopped, a report will be put together, find out problem, being equipment or processing, then reported back to fda, then at that point in 30 days or so fda should give response.... seventy plus percent of batch they say looks fine, it was 27% that didn't hold out......the batch cost one million to make, they might have to throw it all out and start over.....
Rico
Was reading the message board on the day traders on Auxilium, it is a hoot:).....I do find these guys get to know enough about a company to be dangerous, and you have to take there post with a pinch of salt, the shorters of the stock of course have a gain to be made to run down the company, same as the people long in the stock...
I guess a hedge fund drop thiere position in the company on the 5th...might of knew of something, but again companies do sell off prior to year end for tax purposes, might be timing...and the stock has performed well in the last three months, up 100%+, so why not take profits...
What made me laugh is that they don't refer to it as the dupeytren contracture company, but the bent dick fixer..... one shorter said your better off fixing your bent dick with a sledge hammer:)....
Over all I don't think the company did that bad on the news....if you are a buyer of the stock and like it at $16., well you should love it at $13....it close today above $14...... or one can invest in sledge hammers:)
Rico
Funny stuff Rico.
This is my first post, so please excuse me if I am not 'in place.'
I have been looking at this AA4500 development and just wondered if this may actually be a blessing in disguise. I mean, does anyone know if this is something that may convince/allow the FDA to excuse the Phase 3 trials because of ethical matters associcated with placebo's (?) needels in the penis and QC? Could this perhaps, allow for AA4500 to be released for Peyronies Disease before DC? Maybe I am just hoping too damn much!
This may not make anysense, but it was just a thought. Thanks for a great forum to see and share ideas.
;D
I wish you were right. I'm afraid everything will be delayed. But, I don't know.
Great post (in the right place). WELCOME
Liam
Thanks Liam! ;D
I hope it comes out soon though....any other thoughts?
Have a great night!
You may not have seen my post a couple of weeks ago. They called me to do the Dupuytrens trials. It was in Atlanta and I live on the gulf coast of Alabama and could not commit. Maybe a good thing. I told them I was still interested in the Peyronies Disease trials.
I am getting the feeling that this auxilium is a pump and dump.
I believe the research is solid behind Auxilium's AA4500, it was with another company and they picked up the ball so it has a lot of funding behind it as of now and WAS in the third stage......the processing of the drug or storage seems to be the issue and one would think they can get there arms around this soon and re issue it....
Sitting on the sidelines with a bent dick and being second in line to dupuytrens trials is frustrating for everyone....Hope is all we have and to take this away at Xmas is a sad thing.....it will be several months before we here anything, and I guess to try to stay positive.....
I myself don't know or think that aa4500 will be a cure for me....the hour glass is a tough issue to deal with... I hope that more ED drugs and drugs like aa4500 are in development, the better chance we all have in some day finding a better solution to our problem....
Auxilium has there back against the wall....I find for myself when this happens to me I do better with the task at hand...this is the only chance they have right now to stay in the market place,none of us know if it will work for us...but if it helps some of the brothers then this will be good and once again all research in the area of peyronies is a good thing....
The Chinese wall will be crossed soon also, if they can't fix the problem, well you will see this in the stock price.....loose lips sink ships and companies can only blow sunshine up your rear end for so long......aa4500 for peyronies....2009..maybe:(....
auxl is there stock symbol...one can go to yahoo finance and put this in symbol look up and go to message boards ect..... sometimes the street tells you more...but again these day traders...well take them with a pinch of salt also:)...
Rico
Happy New Year.... I Hope. (This post effects us all, and I believe would be appropriate under all threads)
First off, let me extend my appreciation to the founders of this forum and their continued vigilance to freedom of speech of the Peyronie's Sufferers.
I have not posted on the forum much or for very long. However, I believe that there is something that we all may be missing, and for that, we will NEVER achieve our goal of complete rehabilitation.
Please allow me to explain. The 2 drugs in 'development' that hold any real hope for any of us are AA4500 & Pirfenidone (sp?). Furthermore, under new trade initiatives with Latin America, it will soon be ILLEGAL to buy VITAMIN E! (Or any vitamins whether they work or not are a debatable even among experts, but should it prevent us from trying?)
These remedies will never be allowed to reach the very people that we need these products, us. Here is why....
1) Pirfenidone (by Intermune) is largely controlled by 'Warburg, Pincus Equity Partners, L.P. and its affiliates' –
12/28/06 S-3
Registration Statements
2)
a) Warbug is one of the fundamental architects of the Unconstitutional Federal Reserve System created in 1913.
b) THERE ARE CUTTING EDGE MEDICAL TREATMENTS FOR ALL CONDITIONS THAT HAVE BEEN SUPRESSED BY THE RULING ELITE THAT ALLOW FOR, NOT ONLY THE CURES FOR ONCE THOUGHT TERMINAL/LIFELONG DISEASES, BUT LIFE EXTENTION TECHNOLOGY.
3) AA4500 (by Auxilium) is largely controlled by 'Perseus-Soros BioPharmaceutical Fund, LP" -- (the information is in the SEC filings on their own website, look at it -- )
Form SC 13D/A
AUXILIUM PHARMACEUTICALS INC filed this Form SC 13D/A on Dec 11, 2006
a) George Soros is a former member of the Board of Directors of the Council on Foreign Relations. This group is an instrument of the Federal Reserve System and its partner the Bank of England to create World Government.
All of this information is Documented Fact. I wish there was a magic pill we could take. I have lost a lot of sensitivity, size in length and girth, and a huge amount of emotional worth.
It is imperative that you understand this for yourself and do you own research. The best place to start is by watching the free Google video from Aaron Russo (who directed Eddie Murphy and Dan Ackroyde in 'Trading Places' among numerous other accomplishments) and sign the petition to abolish the Federal Reserve System.
Commonly said is...'trying the same think over and over again is the definition of insanity"
If we don't truly see why we have not had any solutions to our problems, they will never be forthcoming.
http://www.freedomtofascism.com/ -- it is free
I wish you all peace and success in this New Year!
???
>> it will soon be ILLEGAL to buy VITAMIN E! <<
Unless I missed something, my vitamin E comes from Utah, and will not be affected by a trade agreement with South or Central America.
The profitability of a drug will definitely affect it's likelihood of being developed. A larg(er) pharmaceutical firm is not likely to even try to do something for which they will not make a sizable profit. As many of us as there are, we will never compare to the numbers of those with heart disease or diabetes. Our disease will remain an "orphan" disease (though it is true that far more suffer from Peyronies Disease than is suspected).
Much of the rest of what you say, like:
" ...Pirfenidone (by Intermune) is largely controlled by 'Warburg, Pincus Equity Partners, L.P. and its affiliates'... (and) ...Warbug is one of the fundamental architects of the Unconstitutional Federal Reserve System created in 1913."
and
"THERE ARE CUTTING EDGE MEDICAL TREATMENTS FOR ALL CONDITIONS THAT HAVE BEEN SUPRESSED BY THE RULING ELITE THAT ALLOW FOR, NOT ONLY THE CURES FOR ONCE THOUGHT TERMINAL/LIFELONG DISEASES, BUT LIFE EXTENTION TECHNOLOGY."
These strike me as conspiracy theory stuff, and I would prefer that such theories, even if "true", be moved to the "off-topic" area for discussion.
Tim
They guy who wrote the original post is a bozo
JV- Here is a link to a SOD, a spray
http://www.youngagainproducts.com/OurProducts/tabid/4206/CategoryID/4/List/1/catpageindex/5/Level/1/ProductID/60/Default.aspx?SortField=ProductName%2cProductName
However, it's not liposomal SOD, so unlikely to penetrate into deeper tissues. On the progression header, there is a possible supplier of liposomal SOD.
AUXL has put out there 8k.... you can download it on Edgar on line.... they talk about the "meltback" of lyophilized cake was detected and the trails stopped on aa4500 in December.... they are trying a couple of techniques to see if they can correct this with a new batch....
They did say that trials for peyronies phase 11b will start in 2007.... this trial is to get the dose right... then of course will be phase 111.... and the beat goes on........
This discussion seems to be converging on something I've believed for a long time, which is that the only route to a solution for Peyronie's would be a drug with systemic antifibrotic action. I also have Dupuytren's and have been following news and discussion on that condition for about 10 years now. In all that time, I've seen exactly one credible report of reversal, and it came from a person with IPF who'd been participating in a trial of Pirfenidone.
With Dupuytren's - unilike Peyronie's - there's just no fooling yourself about the efficacy of a treatment. Your fingers either get staighter or they don't, it's easily and objectively measured. That person who took Pirfenidone had no expectation that it might affect his Dupuytren's - that came as a surprise. Conversely the trial participants weren't selected because they had Dupuytren's and probably few of any other participants had that condition. So our sample size is 1, but it's a valid sample, and we have a huge number of controls, who've tried countless other medications or supplements againt Dupuytren's with no results.
Pirfenidone has come up now on multiple posts. This is just the kind of situation that fills me with frustration. Just go out and google Pirfenidone. You come up with a plethora of hits, some skeptical, but most extremely positive. Same when you do a search on PubMed archives. So here we have a drug with a huge degree of promise for a wider range of fibrosis sufferers than one can imagine, and people are dying, and we have to wait while all the i's are dotted and t's crossed in terms of research before we can get access to it. Truly something is wrong with this system. People who are late stage terminal should have access to promising treatments even if they haven't been run through all the trials. Not to allow this is morally repugnant. Well thats my little rant. Aside from that, this is truly the most promising thing in sight beyond Pentoxifylline. It should be at least fast tracked if it is not already. At least they have given it orphan drug status. The case that j points out in his post below is just so typical. You would think things like that would ring some sort of bell, but unfortunately the people who make the decisions seem to be pretty hard of hearing on these things. What is interesting to me, is that all of the testing that has been done, has been done with Pirfenidone alone. Who might imagine what could be accomplished by combining this drug with other substances that attack other common vectors of fibrosis. Don't get me wrong. I DO believe in the FDA approach of thouroughly testing every aspect of new treatments through a system of well designed multi-stage trials. But, as I stated above, I really believe that we desperately need a department of experimental medicine for dying people who are willing to voluntarily submit themselves to experimental treatments, followed by complete outcome analysis. And I believe that much could be learned from such an approach as well, both positive and negative.
By the way, check this out:
http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100231 (http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100231)
http://www.clinicaltrials.gov/ct/show/NCT00287729 (http://www.clinicaltrials.gov/ct/show/NCT00287729)
And I could give examples with liver fibrosis as well, there is just all kinds of activity going on with this drug.
And note the title of this study:
"Pirfenidone inhibits inflammatory responses and ameliorates allograft injury in a rat lung transplant model"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16153939&dopt=Abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16153939&dopt=Abstract)
"inhibits inflammatory responses" ... hmm ... why do all paths seem to lead back home? In any case this drug is hugely important for Peyronies sufferers, because we will likely be next after the more serious diseases are addressed. Don't assume that the manufacturer will not want to increase their market scope by recruiting Peyronies sufferers as potential customers. This could actually be the breakthrough we are all waiting for.
- George
Google on "pirfernidone intermune lawsuit" and you'll see the real story.
http://www.findarticles.com/p/articles/mi_m0EIN/is_2003_March_25/ai_99165792
http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=ITMN&script=410&layout=6&item_id=446317
In 2002, the rights to pirfenidone were bought by a company called Intermune. Intermune had a competing drug, Actimune, and they wanted to end the competion from pirfenidone, so they simply made it unavailble by buying the rights and sitting on them. They were successfully sued by a man who had IPF and had been staying alive by taking pirfenidone. A setttlement was reached in which Intermune grudgingly agreed to do an FDA trial and make the drug available on a limited basis as part of the trial, so that people already dependent on the drug could stay alive, as inconvenient as that might be for Intermune.
On this basis it seems likely that pirfenidone will remain "in trials" as long as Intermune owns the rights to it.
George,
Thank you for your rant, which expresses pretty much exactly how I feel. Had I been eligible for the clinical trial on pirfenidone, which I doubt due to having other respiratory conditions, I would have had to stop taking any drugs which might conflict with the study's "purity". This includes pentoxifylline, and possibly L-arginine and Vitamine E. In addition, I would have only a 50 percent chance of receiving the pirfenidone, as opposed to the placebo. On the other hand, had I been offered the pirfenidone with no strings attached to take and see how well I did, I would have taken it in a New York second.
I am also aware of the problems with the the company owning the rights to pirfenidone, but since their competing drug has not worked out too well, the clinical trials on pirfenidone may be forthright and honest. However, the problem of drug companies "sitting" on drugs until they are ready to sell them is all too real.
To paraphrase the quote about the legal system, "the mills of clinical research grind exceeding slow but exceeding fine."
Thanks J and Scott for the added information. So why am I not surprised? What a sad story behind Pirfenidone. These robber barons are out to kill off anything that gets in the way of their wealth machines. And I suppose you also heard of the failed IPF trial on Pirfenidone. They called off the trial in the middle of the process because all the participants in the placebo group were dying like flies (none of the members of the Pirfenidone group died). So what do they do? They basically stamped the trial a failure and couldn't figure out where to go from there. Apparently now things are underway again, but as you say, when a company wants to kill a product they just sit on it forever and declare gleefully that it 'needs more study'. Shame on you guys! Here you got me started again. Too bad there isn't some way we could form an alliance with the CKD, IPF, and other fibrosis advocacy groups and really put the heat on these people. But at least the power base is changing in Washington. Finally, I am hearing about a congressional proposal for a new law to prevent the major drug pushers from PAYING generic vendor to NOT produce generic versions of their flagship products AFTER their IP rights expire. Can you believe that they would do an underhanded thing like that? What a perverted implementation of capitalism. :'(
One added note - It would be a VERY GOOD THING if Pirfenidone gets approved soon for IPF. Know why and how that would affect us? Because once Pirfenidone gets the nod as an approved drug for ANY purpose, that means that cutting edge docs like Lue will have the option of prescribing it for Peyronies (or other MDs for CKD, ect.) as an 'off label' use. Much, much simpler than trying to prescribe a drug that is still experimental, because at that point, at least the major safety issues are pretty much addressed. Also a bad thing that could turn out to be a good thing in the case of Pirfenidone is the fact that some people have actually been using it for quite a few years without any negative health effects. All that lays down a solid safety record for the day that it does get approved and makes it more likely that Peyronies sufferers, at least those with the most severe symptoms, will be able to get their hands on it fairly quickly. So, after all, the picture may not be that bleak. Apparently, now, at least, Intermune has gotten the message.
- George
Folks,
'Take the Red Pill' - Matrix Movie
I understand that it may be scary to think that there are forces that you are not aware of prohibiting you from accomplishing your goal. 'Our Goal.'
What floors me is that one can attack another for FACTS that are unknown to them. This is just the tip of the Iceburg. I am at a Library Comp. and only have a little time, so here it is.
Let's get our 'cure' or treatment so that we can live happy sex lives again. I love you all.... :-*
***********************************************************
Anti-Aging Molecule Discovered
Korea Times | January 1, 2007
Kim Tae-gyu
A team of South Korean scientists on Sunday claimed to have created a ``cellular fountain of youth,'' or a small molecule, which enables human cells to avoid aging and dying.
The team, headed by Prof. Kim Tae-kook at the Korea Advanced Institute of Science and Technology, argued the newly-synthesized molecule, named CGK733, can even make cells younger.
The findings were featured by the Britain-based Nature Chemical Biology online early today and will be printed as a cover story in the journal's offline edition early next month.
``All cells face an inevitable death as they age. On this path, cells became lethargic and in the end stop dividing but we witnessed that CGK733 can block the process,'' Kim said.
``We also found the synthetic compound can reverse aging, by revitalizing already-lethargic cells. Theoretically, this can give youth to the elderly via rejuvenating cells,'' the 41-year-old said.
Kim expected that the CGK733-empowered drugs that keep cells youthful far beyond their normal life span would be commercialized in less than 10 years.
Other researchers here heaped praises on the discovery but they were cautious about the practical therapeutic application of the new substance.
``Obviously, it is an innovative finding. But we need to see whether or not CGK733 could really rejuvenate cells inside human bodies without generating side effects,'' Prof. Kim Sung-hoon at Seoul National University said.
Prof. Kim Tae-kook, however, is confident about the commercial viability of CGK733, believing the efficiency of the material was created using state-of-the-art magnetic nano-probe technology.
``We have the magnet-associated technology to identify molecular targets inside living cells, which allowed us to examine the mechanisms of CGK733 directly,'' Kim said.
``Unlike other research teams that must make candidates materials for drugs without being able to see their intra-cell activities, we know the precise mechanism of CGK733. So we have the better chance of making a success of the substance,'' he continued.
Indeed, Kim basked in global recognition last June when he and his associates developed a technology dubbed MAGIC, short for magnetism-based interactive capture.
MAGIC uses fluorescent materials to check whether any drug can mix with targeted proteins inside the cell. The results were globally recognized by being printed by the U.S.-based journal Science at the time.
``MAGIC is kind of a source technology to see inside cells. Based on the method, we also found a pair of promising substances that can deal with cancers,'' Kim said.
Truly fascinating technology, but I'm not sure just how it would relate to Peyronies ???. We've had a number of 19yr olds posting on this forum and I am sure that they are NOT suffering from cell aging. In fact very young people (down to pre-teens) suffer from various forms of fibrosis and attacking cell aging is not a likely solution. There are developmental drugs that DO attack fibrosis, but this is not one of them. For those that are interested, here are the relevant links for 'The Red Pill':
http://eport2.cgc.maricopa.edu/published/v/va/vvalente43/weblog/1/
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_IUDs=16767085
- George
I've been surfing the web (all peyronie-related site) for the past 10 years, trying manual techniques, and the vitamin-bazare, and I can only conclude this :
There have been studies, trials, and so called 'miracle-meds in development' for as long as I remember (over 10 years) & I can only conclude : Don't get your hopes up, you WILL have to live with it. ;)
Julien, with all due respect, I think you are being overly pessimistic. Medical science is only now beginning to unravel the secrets of fibrotic diseases. And the medications to do the job do take a long time to develop. There are scientific issues and political issues involved. But we are closer to a solution now than we ever have been before and you can take that to the bank.
- George
George,
Although I appreciate your enthusiasm, and generally agree with your optimistic outlook, Julien has a point. I would say I have the same point - the only difference is that I have been scouring the medical literature for over 30 years now, and I have had my hopes soar and be dashed. And so it is easy to imagine it will always be the same.
But Julien, remember that right now is a fertile time in the field of biology, and that new insights into the mechanisms of Peyronie's are finally being gleaned. This means that, in turn, ne treatemtns that hold out hope for all of us are on the way.
My point is that Julien is right - we WILL have to learn to live with it. But George and Old Man are right too - they and others who have been able to reverse their Peyronie's without surgery show us that something CAN be done about it.
Tim
Hmmm...
If Intermune actually does continue "squatting" on a very promising drug (Pirfenidone)....
...and...
Intermune is a public company ("ITMN" on NASDAQ)....
...then...(just a thought)... if enough people in the Peyronie's, Duputytren's, & IPF online communities each bought just a couple of shares of their stock...
Control is Powerful. It's something to discuss.
http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=ITMN&script=2100
They claim to be moving forward, but if they don't...
I keep reading about Harvard scientists and Dr. Anthony Atala at Wake Forest creating rabbit penises from their own cells, but they seem content to experiment on other animals instead of conducting human trials. How would subjects be chosen for any future human trials, and have prominent Peyronies Disease docs like Lue, Levine, Mulhall, etc. shown any interest in this field? Finally, what is a realistic guess as to when a human penis will be grown, and which biotech companies might jump in to give the whole thing momentum?
Robert
An exact duplicate of this post under "Urologists and other Doctors" was deleted as a duplicate post.
Hawk
auxl CEO will be on a conference call on the Feb 8th and there will be another(earning report) on the 15th.... the 8th will be replayed for a week on the auxl site on Yahoo finance.....
The Harvard scientist was Anthony Atala - and then he moved to Wake Forest.
The penile recontruction was a "proof of priniciple" experiment that he conducted to demonstrate that it could be done. He has focused more of his attention on simpler organs that are more devastating to people when they malfunction (or so they think!). He has been creating artificial bladders, and may contruct an artificial uterus that could carry a fetus to term. This is all big stuff and is out of the league of scientists like Lue, Levine etc. When he gave a talk recently here he gave no indication that he intended to do any more work with penis surgery. But he has a big lab, and some eager trainee will probably pick up the ball and run with it.
Tim
Dear forum members,
I just listen to the CEO from AUXL... Mr. Armando Anido.... he address the company and different applications for the aa4500... he address the peyronies and said at this time the FDA is having them do a study with animals to see if the aa4500 misses the plaque when the doctor injects it into the penis, what happens to normal tissue.... once this study is done and FDA lets them move forward then they do the two b phase which is to see if 6 or 9 injections are needed.... then a questionaire filled out by clients and they feel they should be able to license the product to the public after this...
The drug aa4500 is not in the clinics now since it was pulled in december for manufactoring problems.... they are working with the FDA to correct this for they can go back to phase three with the frozen shoulder and hand trials....
It was nice to hear the call and peyronies brought up to the financial community and that someone is working on it a least..... he did say that after phase 11b and the questionaire that the FDA should let it go to the public.... so with luck it could be a year or so..... I still don't know if it will help with lost size or waisting, but it should help with bend....
Rico
Rico,
Good update thanks.
One issue - If they have not yet started with animals; they will never do the animal studies, plus the human trials, and questionairs, and be done in anything close to one year.
Hawk,
Good point, it could still be awhile. I listened in on the conference call for a bit, only part of it was spent on peyronies. It seems they are looking to try a new format for the shots, 2 per week, then a 6 week break until the next shots. I'd encourage everyone to listen in on auxilliums webpage. It does seem positive that they are moving forward at least and aren't giving up on the drug. They seem to think that after the animal study which really needs to be done for safety(we don't want to inject this medicine and destroy healthy erectile tissue) as much as we grip about it, and after the next phase studies, this product will be at market.
ComeBackid
Hawk when I listen to the call it sounded like the animal studies where in process... hard to say for sure.... one has to remember that share holders and funds are listening to this call and of course they want to put a positive spin on the company and products coming to market....
The most positive part of the whole thing in my opinion is that they are working with peyronies and bringing it to the attention of more people.... as far as a year, I shouldn't of said that, I have nothing to base that off of other than wishful thinking:)...
Rico
Someone asked when the aa4500 would be on the market on the auxl message board, don't know how accurate this answer is but it was 1st quarter of 2009....two years out:(...
Today there was a documentary on History Channel about sex and technology-Modern Marvel (airing right now as I type). Dr. Atala and his gene therapy research was featured in a segment and it was stated that it should be availble by 2010 to the public.
Keep on Fighting this crap
Power
It will be interesting to see what form that takes, whether there will be human trials for a full replacement or if a scaffolding approach to grow new tunica cells over the damaged will be tried first, and how the existing scarring and fibrosis will be dealt with in that case. I'm just wondering if there's some way for this forum, the APDA or someone with clout acting as a representative to access a contact there at Wake Forest to alert us if there are to be trials, or at least how the preliminary research is progressing other than the infrequent press releases/conferences.
Robert
Thats a neat idea RCRJ, to grow new tunica cells over the damaged ones, perhaps they could be injected into the penis? But yeah we should think about contacting Dr. Atala, he seems to be really on our side, and interested in this stuff. Perhaps he doesn't realize just how many guys out there have peyronies, and how desperate we are. We do have a director of advocacy but hes been inactive for awhile, I hope everything is ok with Blink, perhaps someone new should fill in for him that has the energy to run with the ball?
AUXL just had there earning call and the CEO talked about peyronies and aa4500, he said that phase two B should be in place by fourth quarter of this year and then the bla study for the fda in fifteen months followed by fda approval in another 12 months, so 2010 looks like when it would be ready for market.... the formation or melt back of aa4500 and the need to learn how to extend drying to reduce moisture set it back a good year:).... the animal studies are not complete yet for the fda on what happens to normal tissue also if it misses the plaque...
Received an email from Auxilium with some new information concerning their phase III trials on AA4500 for Dup.
http://phoenix.corporate-ir.net/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=964735&highlight=
Keep Frighting,
Power
Power, thanks for the info. It looks like there were enough patients who completed their treatment with AA4500 in Phase III prior to the early termination of trials to determine its effectiveness and safety. That's the good news. The bad news is that Auxilium predicts trials for peyronie's & dupuytrens will not begin again until Oct-Dec 2007. Keep the faith.
I agree that the conference call and reports are positive, but like mark501 said they aren't even going to start again till the fourth quarter of 2007 and the CEO said that it will be anouther two years for peyronies to be available to the market, and this is if the FDA approves it, they still have the animal testing to complete to see how it affects normal tissue... I guess three years from now is better than nothing:(...
I just got this news in a Google alert!...here's the link http://biz.yahoo.com/prnews/070221/nyw034.html?.v=84 (http://biz.yahoo.com/prnews/070221/nyw034.html?.v=84)
As you can see in this quote from the story, BTC has close connections with Auxilium:
QuoteAs a result of its research and development efforts BTC has also developed an injectable collagenase for treatment of various diseases or indications. BTC has a development and license agreement with Auxilium Pharmaceuticals, Inc. ("Auxilium") for injectable collagenase for clinical indications in Dupuytren's disease, Peyronies's disease and frozen shoulder (adhesive capsulitis).
Yes this is the aa4500.... it will be available with luck in 2010 for peyronies, this is if it gets passed by the FDA.
I came across this article on pubmed where I periodically check for new articles...
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17325694&query_hl=1&itool=pubmed_DocSum
When I think about this disease process in general, I think the first big break will be the ability to pharmacologically inhibit TGF-beta to halt the abnormal disease process. Further down the road, gene therapy will allow for cells to be redirected to attack fibrotic tissue and increase elastic characteristics of the tunical tissue.
Just wanted to 1) highlight the fact that the disease process that currently is being proposed as being behind Peyronies Disease is generating interest for more research and 2) go on record with my theory so I can say "told ya so" when this stuff is just a thing of the past!
This is Hopeful.. Please tell me what the drug (Pirfenidone)....is??- and how does it work with Peyronies Disease?-any studies that I can read, etc.. how is it administered,
Thank you,
Hopeful
Quote from: kevin on January 31, 2007, 04:12:54 AM
Hmmm...
If Intermune actually does continue "squatting" on a very promising drug (Pirfenidone)....
...and...
http://www.corporate-ir.net/ireye/ir_site.zhtml?ticker=ITMN&script=2100
]
Hopeful,
if you click on the SEARCH button (right next to "Help")
then type pirfenidone
put a check in front of SHOW RESULTS AS MESSAGES
You will find all the information you are requesting. We have a great advantage on this forum having a search feature and it keeps members from having to type he same information over and over again.
If you have any problem just ask. Many of us would be glad to help you with this option since it will help you greatly in researching topics.
REF: Journal Sexual Medicine March 2007 (477-84 & PubMed Abstract 17367443 / Title: Topical Verapamil HCI, Topical Trifluoperazine & Topical Magnesium Sulfate For the Treatment of Peyronie's - A Placebo Controlled Pilot Study // Among the authors are William Fitch MD of Urology Consultants*, San Antonio & WJ Easterling RPH of Prescription Dispensing Laboratories** of San Antonio (this per Blackwell Synergy website). // They studied the same 3 drugs in a 2002 report (with a 3 month protocol). In this new study it was for 9 months: l. verapamil only for the full 9 months, 2. trifluoperazine (trade name: stelazine) for 3 months followed by 6 months of verapamil and 3. magnesium sulfate for 3 months followed by 6 months of verapamil. According to the abstract no patients were given a full 9 months on only trifluoperazine or magnesium sulfate. I wonder why not. Was this study sanctioned by the FDA? Was the FDA consulted before, during or after this study? The magnesium sulfate is the only one of the three available without a prescription. It might be a big challenge to obtain a patent on this inexpensive natural substance. I believe Peyronies Disease Labs & Assoc. holds patents on use of verapamil & stelazine for treatment of peyronie's. This from the Peyronies Disease Labs website today referring to topical verapamil: "This medication provided only by a physician's prescription, is not FDA approved & no formal claims related to efficacy or safety are being made" *Urology Consultants is an office of 5 urologists in the Medical Center area in San Antonio of which Dr. Fitch is the only one named on this study. **Peyronies Disease Labs is a commercial compounding pharmacy located in the Falcon International Bank building in the Stone Oak neighborhood of San Antonio.
This is certainly interesting. Stelazine is an antipsychotic (for schizophrenia) taken orally. It was applied topically in this study? What is it thought to do for Peyronie's?
Fitch and Easterling are the guys that originally gave us transdermal Verapamil. From this abstract, it appears that the other compounds were given to the 'control' group basically as placebos.
I wouldn't be surprised if this new article is nothing but a rehash of the study they reported in 2002. That study also claimed improvement in over 90% of the patients. Based on my own experience and that of many posters to this forum, a number of 0% seems more accurate.
j, yes this is somewhat similar to the 2002 study however it does have a different protocol. The conclusions they draw from their studies do not match the experiences of members on this forum. The abstract mentions 4 groups of patients. I take it from that statement to mean 3 different drugs plus l placebo. I don't feel that the magnesium sulfate & trifluoperazine could be considered placebos as they have both shown some effectiveness in treating peyronie's. I have used magnesium sulfate with good success & no side effects. I also used verapamil with bad side effects. This is a bit odd since both are calcium channel blockers. I think I would be cautious in using trifluoperazine (stelazine) even in topical form. It is a potent anti-schizophrenia & anti-anxiety drug. Peyronies Disease Labs did patent it's use in 2003 (issue date) for peyronie's. They call it a calmodulin blocker. In any case I would like to see offical FDA clinical trials on these 3 drugs separately. Until then I remain skeptical of the conclusions in their reports.
Just a note of clarification. The FDA sanctions and controls study of experimental drugs that are new to the market. They thus make researchers do studies in phases that first dertermine that the drug is not unsafe, and then potentially helpful (for limited uses). Once a drug is approved it can be prescribed by anyone.
After a drug is approved (and some were never studied initially anyway - like aspirin), then one can design a study of it for other purposes. If one creates a new formulation (this might improve, say, drug delivery to tissue - but it might also be patentable!), then that formulation must also pass FDA muster. However, if one is studying an older drug in a novel way, then the FDA is not going to primarily control that study.
I could thus study the role of vitamin E on lung health. I would have to propose a study, find someone to fund it, and get it approved by my Institutional Review Board. If I were in private practice, then the rules are more slack. For instance, a local Homeopath may decide to "study" vitamin E, but not really do a randomized study, or get it to pass muster with an IRB. But that person might find it hard to get published in a peer reviewed journal.
I haven't looked at this journal (Journal Sexual Medicine) lately, but it is definitely second tier in terms of level of quality. It is the kind of place I might submit a paper less likely to be accepted in a "real" journal like Urology.
Tim
mark501, do you have access to the full text of the article? If so, how many patients are they claiming were enrolled in the new study?
Is "Peyronie's Disease Labs" just a new name for their old front, "Prescription Dispensing Laboratories"?
I'll state the obvious question - why have none of these patients (94% of whom saw significant improvement) posted on this forum? And I'll predict that none of them ever will. As was the case with the 2002 study.
J & Tim, Thanks for your input on this subject. Sorry I don't have access to the full article. It does say in the abstract that there were 57 patients "randomized". On the company literature "PDLABS" is in large print & underneath in small print is "prescription dispensing laboratories". I spoke to one of the employees of this company years ago and they told me that to comply with FDA regulations of a clinical trial of their primary asset (topical verapamil) would cost them more than the bank building that they are housed in. The wording "two simultaneous, three armed, double blinded, placebo-controlled studies" sound very impressive at first glance however it does not address the role of each of the 3 topicals independently for a 9 month period. Their stated goal in the abstract is "to assess the efficacy of a 15% verapamil gel". What about the efficacy of the other 2 gels? Unstated at least in the abstract is the percentage (strength) in the magnesium sulfate gel & the trifluoperazine gel.
Quote from: mark501 on March 23, 2007, 09:38:06 AM
I spoke to one of the employees of this company years ago and they told me that to comply with FDA regulations of a clinical trial of their primary asset (topical verapamil) would cost them more than the bank building that they are housed in.
My guess is that it would cost them more than that. I suspect it would demonstrate the ineffectiveness of their product and cost them their business.
So Mark, please tell us what this magnesium sulfate preparation is. The common form of magnesium sulfate is epsom salts, but I take it you are using something more concentrated? ??? So, please give us some information on what you are using and where you are getting it. :P
Thanks,
George
George, I don't know how to make an exact strength comparison between epsom salt cream from www.kirkmanlabs.com & epsom salt granules from Walgreens. Perhaps you can help work the numbers. Kirkman Labs cream: 113 grams in 4 oz. jar; 1 gram supplies 100mg of epsom salt USP (magnesium sulfate heptahydrate); suggested use on label: 1 gram 1-4X daily. Walgreens epsom salt granules (magnesium sulfate USP) Total magnesium - 9.8%, Total sulfur 12.9%. suggested use onl label: dissolve 2 cups of epsom salt (granules) per gallon of water. The label does not say how many mg are in each cup. Perhaps another brand would have this info on their product. My use of the Kirkman product has usually been 2 grams 3x daily.
Mark, I'm not sure strength is the important factor here. Its efficacy can also be related to the formulation itself. The fact, for example, that it is dissolved in a a fatty or oily base rather than in water can make a huge difference in its potential effectiveness. And of course, convenience can be a factor as well. Thanks for sharing the info. This is interesting.
- George
Does anybody know if epsom salts or this formulation could be irritating to the skin or whatnot over time?
Gee and this is the one I have been hoping for. I'd volunteer for this one in a minute I think. This is one reason I hesitate to have a graft or something. I keep thinking that maybe a cure will be coming soon. Looks like this one will be a while.
Quote from: Rico on February 21, 2007, 10:37:40 AM
I agree that the conference call and reports are positive, but like mark501 said they aren't even going to start again till the fourth quarter of 2007 and the CEO said that it will be anouther two years for peyronies to be available to the market, and this is if the FDA approves it, they still have the animal testing to complete to see how it affects normal tissue... I guess three years from now is better than nothing:(...
Auxilium stated today that their "outside of plaque" animal study is to be completed this summer & the results forwarded to the FDA then. If I understand correctly they are saying that in Dupuytren's, a 5 degree variance from normal will be considered a success. A measurement of success for AA4500 in treatment of Peyronie's has not been determined yet. They mentioned today that answers from patient questionaires after treatment & consultation with FDA would help define success.
So does this mean human trials by end of the year?
Quote from: mark501 on April 12, 2007, 02:30:20 PM
Auxilium stated today that their "outside of plaque" animal study is to be completed this summer & the results forwarded to the FDA then. If I understand correctly they are saying that in Dupuytren's, a 5 degree variance from normal will be considered a success. A measurement of success for AA4500 in treatment of Peyronie's has not been determined yet. They mentioned today that answers from patient questionaires after treatment & consultation with FDA would help define success.
This may be of interest to some:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17419813&query_hl=2&itool=pubmed_docsum
http://www.cnn.com/2007/TECH/science/05/17/baldness.study.reut/index.html
while completely unrelated to peyronie's there was this little nugget in there that may lend some application to peyronie's:
"Cotsarelis also envisioned treating wounds in a way that would leave skin with hair follicles, sweat glands and other normal attributes that would be functionally and cosmetically much better than a scar."
edit:
full text of the article below
QuoteWASHINGTON (Reuters) -- Mice with deep skin wounds can grow new hair, scientists said on Wednesday in a finding that offers hope for a baldness remedy for humans.
The mice regenerated hair at the site of the wound via molecular processes similar to those used in embryonic development, according to the research, published in the journal Nature.
The findings show mammals possess greater regenerative abilities than commonly believed. While some amphibians can regenerate limbs and some reptiles can regenerate tails, regeneration in mammals is far more limited.
Dr. George Cotsarelis, a dermatology professor at the University of Pennsylvania School of Medicine in Philadelphia who led the study, said the findings dispel the dogma that hair loss is permanent in people and other mammals, and that once they are lost new hair follicles cannot grow.
Cotsarelis said the findings could pave the way for remedies for male-pattern baldness and other types of hair-loss. He said the idea would be to apply compounds to get epidermal cells to turn into hair follicles.
The regenerated follicles functioned normally, cycling through the various stages of hair growth, and the hair was indistinguishable from neighboring hair with a key exception -- it lacked pigmentation and was white.
The otherwise brown-haired mice had patches of white hair marking the site of the wound.
Cotsarelis said the white-hair issue may not materialize in any baldness remedy in people because the human pigmentation system differs from that in mice.
The researchers made relatively large wounds on the backs of adult mice, and found that if a wound reached a certain size new hairs formed at its center, with the skin undergoing changes mimicking stages of embryonic hair-follicle development.
Dormant embryonic molecular pathways were activated, sending stem cells -- master cells able to transform into other cell types -- to the damaged skin.
The stem cells that gave rise to the regenerated follicles were not stem cells usually associated with hair-follicle development.
"They're actually coming from epidermal cells that don't normally make hair follicles. So they're somehow reprogrammed and told to make a follicle," Cotsarelis said.
The researchers also found a way to amplify the natural regeneration process, causing mice to grow twice as many new hairs by giving the skin a specific molecular signal.
Cotsarelis is involved with Follica Inc., a privately held start-up company that has licensed the patent on the process from the University of Pennsylvania. He said it probably would be more than five years before a treatment was possible.
Cotsarelis also envisioned treating wounds in a way that would leave skin with hair follicles, sweat glands and other normal attributes that would be functionally and cosmetically much better than a scar.
Dr. Cheng-Ming Chuong, a professor of pathology at the University of Southern California who was not involved in the study, said it proved the principle that hair can regenerate from adult skin, but cautioned that human skin differs from mouse skin.
"Repair and regeneration appear to be in competition," Chuong said by e-mail.
"Since fast-closing wounds help the survival of wild animals, repair often dominates regeneration. In the practice of medicine, physicians are trained to close wounds as soon as possible, thus leaving not enough time for regeneration to occur."
Jon,
That link is worthy of discussion but you should probably summarize it. CNN will move or delete the story and the link will go inactive on the CNN site. No one will have a clue what you were in reference to.
Hey Guys,
Seems like AA4500 will come to fruition (though its taking a while). Keep fighting and strive to keep the body as optimal as you can, so when the time does come around, the treatment can do what it does best..bye bye collagen!!!
Check the link out below:
http://www.chron.com/disp/story.mpl/ap/fn/4835578.html
God Bless,
Power
I am personally quite suspicious of this company and their practices. I have seen more that is directed towards increasing market share value and less towards development of a genuine product. Buy now? I will pass and accept a loss gladly if I can see a product that works.
I am starting to wonder if this company is all hat and no cattle.
Tim
Hey Tim,
Sorry you feel that way. Understandable though. I have some suspicions my self.. Suspicions that you may be one of the first in line to get it, if and when it does reach the market. ..I'll see you in line.. hahah.
But for real. They really need to get the whip cracking on this AA4500. I personally, prefer to keep hope alive, irregardless of the company's profit aspirations.
God Bless,
Power
Well, living in America, I don't mind a company trying to increase it's market share, but only if it's by bringing out a worthwhile product...not by bringing out promises only! Time only will tell if/when AA4500 will be a savior to all of us or just to Auxilium.
I posted earlier about taking borage oil and vitamin E. While on Vitamin E, I was ramping it up to about 1000 IU and noticed a lot of fatique, mentally especially. I took one borage oil capsule at night along with 400 IU of Vitamin E. The next morning I took one more borage oil capsule. I was studying for a test that morning. About an hour after taking the borage oil, I noticed a very sudden increase in pressure (which can only be described as a once in a lifetime event of a mammoth increase in pressure that did not cause pain however) localized on the left side of my brain. I stopped whatever I was concentrating on and the pressure went down. The increase and the decrease was on the order of 3 or 4 seconds total. It was nearly impossible to concentrate after this during the day on whatever I was studying. During that day, on the very few times that I talked, there were popping sensations in my head, and I had fatigue. I had a test 4 days later, and one where I could easily have concentrated before, it was literally like wading in quicksand in terms of thinking. I could still think but it was very slow. The left side of my head which would activate when I concentrated has only come back minimally. I would have to say that my ability to concentrate, especially in terms of reading material or verbally, has diminished somewhat. It is clear in my mind that I had a blood vessel burst in my head localized in the region that I used a lot, in fact which I was using at the time that it happened. I still have the logical, mathematical abilities, it is just that I literally am disabled when it comes to reading and concentrating on verbal things. It's like there is this blank or void spot in my head that never activates, when I could feel it activating before. I don't mean to sound like I'm bitching, but this is what I believe happened. I remember in the days afterward, when I tried to concentrate like I used to, that there was pain in this region of my head. The only other explanation is that this increase in pressure was a drug effect that shut down this area of the brain, temporarilly, it is yet to see. But I literally feel that I am somewhat disabled.
Quotethere were popping sensations in my head,
Man, I hate it when that happens!QuoteI stopped whatever I was concentrating on and the pressure went down.
This I understand.QuoteI still have the logical, mathematical abilities
I'm not sure about the logical part. This is very very far fetched. Check with your doctor!
QuoteThe only other explanation is that this increase in pressure was a drug effect that shut down this area of the brain, temporarilly, it is yet to see
That is the only thing that would explain nothing. Vitamin E and Bosarge Oil are not drugs, they're supplements. In low doses they are safe. They're not going to cause your brain to bleed. And if they did, you would not be here writing about it. See your doctor and explain your theory. See what he says. Have you considered something like Meniere's Disease ( http://www.menieresinfo.com/start.html ). Another alternative is chronic fatigue syndrome. Lyme Disease and MS could produce those symptoms. There are several psychiatric disorders which could be culprits. Have you been tested for ADD?
I remember the good old days when kids would OD on real drugs and then have coversations with characters from "Through the Looking Glass". :-\
BTW, here's a good link on Aphasia: http://en.wikipedia.org/wiki/Aphasia
Also check www.ASHA.orgAny other discussion on this...... Lets move to Oral Treatments topic.
Liam
When you last checked in, you asked us if using the VED made our penises look like "beat up sausages", which challenges us to state publicly if we are insane or sane, for who on earth would use something that did that to our penises if we were sane?
Today, apparently unconvinced of our sanity (for no one admitted to having their penis look like a sausage after VED use), you are challenging us to believe something that is, um, unlikely and incredible.
I do think that this statement is probably truthful: "I literally feel that I am somewhat disabled."
There are other explanations for your symptoms (if they really happened and you are not simply an attention junkie here making crap up). Migraine headache is a good bet, as is a psychologic impairment of some sort. You could resolve such a question with a trip to a doctor - and one might wonder why a man who was convinced a blood vessel had burst in his head, rendering him disabled, did NOT go to a doctor.
If you genuinely want to learn about Peyronie's Disease, I think it is time to take the cotton out of your ears and stuff it in your mouth. Read here and learn, but such posts are beyond incredible.
Tim
I can't say that it caused a disability. I will try to describe what happened. Do you know when you concentrate, you can sometimes feel the brain activating? Well I was concentrating, and the usual feeling of just activation in the left area of my brain somewhat near the ears was occuring. I'm concentrating, and then suddenly it's like that feeling starts to escalate and escalate and escalate, almost like a blow-out or something. I can't be certain it was a blood vessel burst. Perhaps what was happening was an increase in blood pressure in this area, and that either caused the brain in this area to shut down for safety reasons or there, and I'm speculating, that there was small amounts of blood leakage from capillaries due to the increased pressure. That day, I was literally wiped out and could not probably do anything that required a great deal of thought if my life depended on it, and I don't know how vitamin E fatique could explain that. For the next several nights, in bed, when I tried to concentrate like I used to, it wouldn't really activate and there was pain while trying to concentrate but not without. I've had this area activate again in the past usually when I'm not trying to activate it, like when I am encountering a new situation, and it is somewhat coming back now. Perhaps it is psychological to some extent. But what I don't know is why it was so difficult for me to concentrate and finish the test, as if I had a really bad hangover. I've had vitamin E in the past causing fatique, and making it difficult to concentrate, but nothing like this. I stopped taking all vitamins after this, and yet for several weeks, it was still quite difficult to concentrate in comparision to previous times. It has improved somewhat, though.
I just looked up brain hemorrhage. They say a brain hemorrhage is a sudden increase in pressure within the brain caused by leaking blood. My question to anybody knowledgeable in this area, and I may see a doctor, is, can the increase in pressure be localized to one area of the brain or is the feeling of increase in pressure throughout the entire brain. The feeling I had was in one localized spot in my head which the pressure went down after I stopped whatever I was doing. The link I see says that if there is enough bleeding, it can be enough to cause unconsciousness, which I didn't have. They also say that the bleeding can cause a massive headache, which I didn't have. One of the main reasons I didn't see a doctor, was that I didn't have a headache.
Tdsc, You might want to consider the fact that the pressure referred to in the case of brain hemorrhage is actual physical pressure within the brain. The perceptions of that pressure are as stated in the definition which, as far as I know, do not include the perception of 'pressure'. Simply 'feeling' pressure in the brain could probably be caused by a long list of things, most of them benign. But there is simply no way that one can accurately diagnose one's own condition reliably because to do so takes a lot of objectivity and that is why even doctors see other doctors to diagnose their afflictions. I once was told by a doctor that it is very common in medical school for even doctors to suddenly become convinced that they were experiencing some dread condition simply on the basis that it was something they had recently studied and, from their perceived symptoms, they just knew that they must have had that problem. And it was equally common that they were completely misinterpreting their symptoms. So Tim is right about this. You should run it by your doctor and let him have a chance to be able to ask the right questions to help you understand whether or not this is serious, important or even diagnosable. As you get older, you will find that you will suffer from all sorts of mysterious symptoms that come and go and usually, almost always, amount to nothing. I am not trying to trivialize your concern, I have been in similar situations myself on more than one occasion. But those experiences would indicate to me that you probably have very little to be concerned about. All of our physical perceptions are sensed through the nervous system and the nervous system can and does play tricks on us. That would be one of my first suspicions in your case. Like you, I have felt a sensation of pressure in my head before on more than one occasion. Other than being a bit weird and scary, no negative effects ever resulted from it. When you need to become concerned is when you are experiencing such things as sudden vision problems, or unexplained nausea or dizziness, stiffness or numbness in the extremities, stuff like that. But just to make sure you are not missing something, it is always good to mention these things to your doctor. - George
PS - Trust me, you can die a thousand unnecessary deaths by trying to speculate on your symptoms and to diagnose your own condition. People actually commit suicide simply because they are convinced they have some terrible disease which they don't (didn't) have. So it doesn't pay to try to use the internet to come up with a diagnosis. Do go see your doctor. Its a lot less painful that way.
TDSK - This is NOT a self-diagnosis forum. It certainly is not a self-diagnosis forum for neurological problems. These posts are both beyond the scope of any forum and totally unrelated to, and off topic to this forum. I am certain that your perceived problems have nothing to do with the things to which you attribute them. I am also certain that you need some up-close, hands-on, time with competent professionals.
Please peruse this coarse rather than wasting time with these type of posts.
Good luck.
Auxilium in an SEC filing yesterday are now calling AA4500 by the trade name "XIAFLEX" . In the filing they also restate clinical trials for Dupuytren's to begin 4th quarter of 2007 and for peyronie's Q1/Q2 of 2008. I didn't notice any info on results of out of plaque animal studies but perhaps it will be mentioned later today in their audio webcast. They have a 2d webcast this month; tuesday, July 31 at 9am CDT.
Auxilium stated today that results from the "outside of plaque" animal trials should be available first half of 2008. Even so, the trials for Dupuytrens are to go ahead this year. They claim a success rate of 70% for Dupuytrens with a single 1/4cc injection of XIAFLEX. (3 doses maximum for Dupuytrens) When trials for Peyronie's restarts it may be 6 doses over about a 13 week period.
I just wanted to throw my 2 cents in and say that I am extremely excited about the Xiaflex results thus far. It is hard to be patient but the fact that it has made it to a second phase II trial is good news for all of us. We would not want for this process to be rushed so that we lose this promising treatment altogether!
What I hope for in the future is a treatment such as Xiaflex to address established fibrosis and a preventive treatment targeting the pathogenesis of the disease. Scientific knowledge expands exponentially, and with the biomedical techniques available today being applied to novel medical problems, I have to imagine that we could see this problem solved within 20 years. While that won't be as much help to some of us as others, at least guys in the future wouldn't have to deal with a problem like this because it is awful!
It is promising as well that there are other fibrotic conditions, such as pulmonary fibrosis, that are being researched. Medical therapy aimed at these conditions might produce a treatment that could be adapted for Peyronies Disease treatment. Further, as motivated as our country is to find the fountain of youth I imagine anyone who could find a pharmacologic means to stimulate production of elastin and reduce fibrosis and degradation of elastic tissue would be able to retire at a pretty early age! Don't think there are not people out there working on this day and night! Again, even if their target is skin integrity, low back pain...whatever it is...it may also have efficacy in our condition.
Just a few thoughts...everyone hang in there!
Found this in an emedicine article discussing Dupuytren's...at least demonstrates that there is thought going into prevention as well as treatment:
"Myofibroblasts are the primary cell type in Dupuytren disease and 5-fluorouracil (5-FU) inhibits both proliferation and myofibroblast differentiation in Dupuytren cell culture. Thus, 5-FU has the potential of being used as an adjuvant to reduce the rate of recurrence and contracture (Bansal, 2005)."
Now, that is a chemotherapeutic agent so not sure how feasible it would be to use something like this but who knows?
Does this relate to Peyronies Disease?
Protein Reverses Effects of Cardiac Fibrosis
Jul 30 2007, 11:47 AM ESTGEN News Highlights
Researchers at Beth Israel Deaconess Medical Center (BIDMC) further elucidated the origins of cardiac fibrosis, a scarring of the heart tissue that leads to a variety of cardiac diseases, most notably heart failure. The study also demonstrated that a molecule known as recombinant human bone morphogenic protein 7 (rhBMP7) can reverse the cardiac fibrosis process.
Fibrosis develops when the body's natural wound-healing process goes awry. Under normal conditions, specialized cells known as fibroblasts deposit layers of collagen protein to form a scar and thereby enable wounds to heal. However, in abnormal circumstances and for unknown reasons, excessive production of matrix proteins such as collagen, results in pathological scarring or fibrosis.
The researchers speculated that a specialized form of epithelial-mesenchymal transition known as endothelial-mesenchymal transition (EndMT) might be the mechanism behind this, so using knockout mice in which endothelial cells had been marked genetically, the investigators confirmed that, during cardiac fibrosis, these cells were indeed converting into activated fibroblasts that were depositing scar material and impeding the proper function and electrical conduction of the heart.
In the second part of the study, the investigators turned to the rhBMP7 protein to determine if it could successfully reverse the EndMT process in mice, reducing the development of fibroblasts and improving heart function.
"The rhBMP-7 protein was quite impressive in its ability to recover the function of damaged hearts," says Raghu Kalluri, Ph.D., senior author and chief of the division of matrix biology at BIDMC. "These findings provide compelling proof that the process of fibrosis can be reversed in the heart and offers the possibility of new therapies for patients who have developed cardiac fibrosis as the result of myocardial infarction, hypertension, valvular diseases, or heart transplantation."
The study appears in the July 29 advance online publication of Nature Medicine.
Source: http://www.genengnews.com/news/bnitem.aspx?name=21011920
Moved to appropriate topic.
Liam, this is a really, really, good find. And what was REALLY fascinating to me about it is that this is not the first time I have seen BMP7 mentioned in connection with fibrosis. In fact I am trying to dig it out right now, I know I have it around here somewhere. Well, it was research speculating that it would be useful in treating kidney disease and I have it on one of my computers somewhere and can't find it OR the hard copy. But thats OK since good old Wikipedia actually references the latest on this with their BMP article:
QuoteBMP-7 has also recently found use in the treatment of chronic kidney disease (CKD). BMP-7 has been shown in murine animal models to reverse the loss of glomeruli due to sclerosis. Curis has been in the forefront of developing BMP-7 for this use. In 2002, Curis licensed BMP-7 to Ortho Biotech Products, a subsidiary of Johnson & Johnson.
http://en.wikipedia.org/wiki/Bone_morphogenetic_protein (http://en.wikipedia.org/wiki/Bone_morphogenetic_protein)
So there you have it. BMP-7 being used to treat kidney "sclerosis". For those who might be in the dark, sclerosis is really just yet another term for fibrosis. Plaque, scar tissue, sclerosis, its all just varying forms of fibrosis. So if BMP-7 is useful in treating fibrosis of the heart AND fibrosis of the kidney, what other types of fibrosis might respond to it? Fibrosis of the TA perhaps? Hmmm ...
Another interesting point from the very same article:
QuoteOriginally, seven such proteins were discovered. Of these, six of them (BMP2 through BMP7) belong to the Transforming growth factor beta superfamily of proteins. Since then, nine more BMPs have been discovered, bringing the total to sixteen.
Anybody notice anything curious about this statement? It seems that BMP7 is DIRECTLY related to TGF-beta. Such a coincidence. And could it be that it actually is the perfect agent to turn TGF-beta-1 "off"? - George
PS - I REPEAT ... This is the best time in history to have Peyronies! With all the fibrosis research going on there WILL be a breakthrough soon. Hang in there guys. We are oh so close. Don't let the stuff that doesn't pan out discourage you, there is more on the way. We just have to be as pro-active as possible, encourage each other to see the bright side (and there really is a very bright side), and be informed so that we can have access to the best treatments as they emerge.
Moved to appropriate topic.
George,
The key word to me is reversed as opposed to stopped. Many of our Peyronies Disease progressions have stopped or are inactive. Reversal of the process is what seems so promising (yet still far away). Who knows?
Moved to appropriate topic.
Here is the abstract of the study George mentioned.
Articles by Morrissey, J.
Articles by Klahr, S.
Articles citing this Article
Search for Related Content
PubMed
PubMed Citation
Articles by Morrissey, J.
Articles by Klahr, S.
J Am Soc Nephrol 13:S14-S21, 2002
© 2002 American Society of Nephrology
--------------------------------------------------------------------------------
Pathophysiology of Chronic Renal Failure and Complications
Bone Morphogenetic Protein-7 Improves Renal Fibrosis and Accelerates the Return of Renal Function
Jeremiah Morrissey*, Keith Hruska*, Guangjie Guo*, Song Wang*, Qing Chen* and Saulo Klahr*
Renal Division, *Department of Internal Medicine and Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri.
Correspondence to Dr. Saulo Klahr, Department of Medicine, Barnes-Jewish Hospital (North Campus), 216 South Kingshighway Boulevard, St. Louis, MO 63110-1092. Phone: 314-454-7107; Fax: 314-454-5110; E-mail: sklahr@imgate.wustl.edu
Abstract
ABSTRACT. A prevention protocol has demonstrated that bone morphogenetic protein-7 (BMP-7) blunted the development of fibrosis in a rat model of unilateral ureteral obstruction. This prevention protocol also preserved, to an extent, renal function. The prevention protocol was extended and a treatment protocol used to examine if BMP-7 was beneficial at limiting fibrosis of the kidney when the BMP-7 was administered during the progression of fibrotic disease. Animals were distributed into four groups. Group 1 received vehicle, group 2 received enalapril (12.5 mg/kg body wt per d), group 3 received BMP-7 (50 or 300 µg/kg), and group 4 received both the enalapril and the high dose of BMP-7. Rats underwent reversible unilateral ureteral obstruction for 3 d, after which the obstruction was relieved. In the treatment protocol, 300 µg/kg BMP-7 was given after the release of obstruction. Seven days after release of the obstruction and the onset of treatment glomerular filtration rate (GFR), renal blood flow, and various histologic indexes of fibrosis were determined. On a consistent basis, BMP-7 treatment alone was found to be slightly but significantly (P < 0.04 to 0.007) better than enalapril alone or in combination with enalapril at decreasing interstitial volume or tubule atrophy. BMP-7 treatment was slightly but not significantly better (P < 0.09) than enalapril at restoring GFR in the prevention protocol. Treatment with BMP-7 significantly boosted GFR (P < 0.01) above that seen with vehicle treatment. These results suggest that BMP-7 treatment is capable of blunting the progression of fibrotic disease and of decreasing interstitial volume. Importantly, a return of renal function is accelerated by BMP-7 treatment. These results suggest that administration of BMP-7 may be an effective treatment to restore or preserve renal histology and renal function in this experimental model of renal disease.
http://jasn.asnjournals.org/cgi/content/abstract/13/suppl_1/S14
Moved to appropriate topic.
I decided this is the appropriate topic for these.
http://gut.bmj.com/cgi/content/abstract/56/5/706 - Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VJ0-4N8164H-1G&_user=10&_coverDate=03%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=30cd508329bff5f75e0e797532785874 -The Effects of Rapamycin in the Progression of Renal Fibrosis
------------------------------------------------------------------------------------------------------------------------------------
Papers In Press, published online ahead of print June 11, 2007
J. Biol. Chem, 10.1074/jbc.M700194200
Submitted on January 8, 2007
Revised on June 6, 2007
Accepted on June 11, 2007
Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition
Michael Zeisberg, Changqing Yang, Margot Martino, Michael Duncan, Florian Rieder, Harikrishna Tanjore, and Raghu Kalluri
Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
Corresponding Author: rkalluri@bidmc.harvard.edu
Activated fibroblasts are key contributors to the fibrotic extracellular matrix accumulation during liver fibrosis. The origin of such fibroblasts is still debated, although several studies point to stellate cells as the principal source. The role of adult hepatocytes as contributors to the accumulation of fibroblasts in the fibrotic liver is yet undetermined. Here we provide evidence that the pro-fibrotic growth factor, TGF-beta1, induces adult mouse hepatocytes to undergo phenotypic and functional changes typical of epithelial-to-mesenchymal transition (EMT). We perform lineage-tracing experiments using AlbCre.R26RstoplacZ double transgenic mice to demonstrate that hepatocytes which undergo EMT contribute substantially to the population of FSP1-positive fibroblasts in CCL4-induced liver fibrosis. Furthermore, we demonstrate that bone morphogenic protein-7 (BMP7), a member of the TGFbeta superfamily which is known to antagonize TGFbeta signaling, significantly inhibits progression of liver fibrosis in these mice. BMP-7 treatment abolishes EMT-derived fibroblasts, suggesting that the therapeutic effect of BMP7 was at least partially via inhibition of EMT. These results provide direct evidence for the functional involvement of adult hepatocytes in the accumulation of activated fibroblasts in the fibrotic liver. Furthermore, our findings suggest that EMT is a promising therapeutic target for the attenuation of liver fibrosis.
Source: http://www.jbc.org/cgi/content/abstract/M700194200v1
------------------------------------------------------------------------------------------------------------------------------
Here's a repeat from a different source:
A new injectable mixed collagenase (AA4500, Auxilium Pharmaceuticals) was studied in two 12-month open-label studies to determine reduction in penile curvature and improvement of sexual quality of life in men with Peyronies Disease. Results from the studies were pooled for analysis (n = 35).[9] In both studies, sets of 3 injections over 7-10 days were given in different sequences over 6-12 weeks. At 9 months, 89% of patients had achieved clinical success; baseline angle of deviation improved by a mean of about 25°, all had pain-free erections, and other distressing physical symptoms improved. The size of the plaque, however, did not change significantly. Local adverse effects related to the injections did occur, but there were no generalized problems. Larger controlled trials are planned.
Source: http://www.medscape.com/viewarticle/559060
roadblock, an English reconstructive surgery group called the Raft Institute tried 5-flourouracil on Dupuytren's several years ago, but did not see an effect.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WJM-4BFX2KS-8&_user=10&_coverDate=02%2F29%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4cf406ea50f3ab4f1ef988161ae57339
Well Liam, here is another fascinating one:
QuoteBone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells.
Wang S, Hirschberg R.
Harbor-UCLA Research and Education Institute, UCLA, Torrance, California 90502, USA.
Bone morphogenetic protein-7 (BMP7) is expressed in adult kidney and reduces renal fibrogenesis when given exogenously to rodents with experimental chronic nephropathies. In mesangial cells that regulate glomerular fibrosis in vivo, BMP7 inhibits transforming growth factor beta (TGF-beta)-driven fibrogenesis, primarily by preventing the TGF-beta-dependent down-regulation of matrix degradation and up-regulation of PAI-1. The signals and mechanisms of the BMP7 opposition to actions of TGF-beta are unknown. Here we show in mesangial cells that BMP7 reduces nuclear accumulation of Smad3 and blocks the transcriptional up-regulation of the TGF-beta/Smad3 target, CAGA-lux. Smad5 knock-down impairs the ability of BMP7 to interfere with the activation of CAGA-lux and the accumulation of PAI-1 by TGF-beta indicating that Smad5 is required. Smad5 knock-down also reduces the rise in Smad6 upon BMP7. Forced expression of smad5 (found to be the preferred BMP7-induced receptor-activated Smad signal in mesangial cells) or of smad6 mimics BMP7 in opposing the increase in transcriptional activation of PAI-1 and its secretion upon TGF-beta. This suggests a model for the BMP7-induced opposition to TGF-beta-dependent mesangial fibrogenesis requiring Smad5; the model involves the inhibitory Smad6 downstream of Smad5 as well as reduced availability of Smad3 in the nucleus. BMP7 does not require signaling through Erk1/2, p38, or JNK and does not utilize the TGF-beta transcriptional co-repressors Ski or SnoN in mesangial cells. These studies provide first insights into mechanisms through which BMP7 opposes TGF-beta-induced glomerular fibrogenesis.
PMID: 15047707 [PubMed - indexed for MEDLINE]
- George
Moved to appropriate topic.
Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis.http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17665426&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Post was edited. Subject and title added to link.
Inhibition of TGF-beta induced lung fibroblast to myofibroblast conversion by phosphodiesterase inhibiting drugs and activators of soluble guanylyl cyclase.http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17659276&ordinalpos=42&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Post was edited. Subject and title added to link.
QuoteA new injectable mixed collagenase (AA4500, Auxilium Pharmaceuticals) was studied in two 12-month open-label studies to determine reduction in penile curvature and improvement of sexual quality of life in men with Peyronies Disease. Results from the studies were pooled for analysis (n = 35).[9] In both studies, sets of 3 injections over 7-10 days were given in different sequences over 6-12 weeks. At 9 months, 89% of patients had achieved clinical success; baseline angle of deviation improved by a mean of about 25°, all had pain-free erections, and other distressing physical symptoms improved. The size of the plaque, however, did not change significantly. Local adverse effects related to the injections did occur, but there were no generalized problems. Larger controlled trials are planned.
Source: http://www.medscape.com/viewarticle/559060 Free registration.
Yes, I'm quoting myself. Does any one have a direct link to the results?
This report is giving me problems on so many levels. On the surface it is very promising. I am hopeful. But that skeptic in me asks the questions. If they are using collogenase, why didn't the plaque "breakdown"? If the average was 25 degrees improvement, what was the range?
I would (and my name is in the pot) volunteer as a subject in the trials. This report just made me pause.
http://ir.auxilium.com/phoenix.zhtml?c=142125&p=irol-eventDetails&EventId=1599870
I wonder if posts about developmental cures and research on associated disorders, should be posted under Developmental drugs and treatments - (Still in trial or not approved for Peyronies Disease)
We have discussed fibrotic conditions like Dupuytrens Contracture, fibrosis of the heart, kidney fibrosis, just to name a few. They all have related issues such as inflammation, and most mention TGF-B1.
Well, I was just doing a fast look-up on Cirrhosis of the liver for a friend. I was interested when it said that it was caused by an inflammatory reaction that resulted in the progressive formation of fibrotic scar tissue that interferes with normal liver function. I was startled however when it indicated that one of the many symptoms or associated complications is Dupuytrens Contracture.
The picture becomes more and more clear that most if not all fibrotic conditions seem to have clear common components. Also, inflammation seems to be the root of an incredible range of disorders from vascular disease to cancer. While this gives some hope, we cannot wait while a yet undiscovered cure for some associated fibrotic condition trickles down to us. Between the discovery and the trickle it will be a long wait. We need Peyronies Disease specific research.
Moved to appropriate topic.
Hawk, I think you are absolutely right. The "Open Questions" and "General Comments" areas are notorious for drifting along and then, seemingly without warning, drifting over into one of the previously designated topic areas and focusing on it. This seems to happen when such a subject gets gently touched on and others of us dive in and share our knowledge/discoveries/thoughts on the same subject. This is when it becomes necessary for you (or Liam) to come along and move the specific clump of posts, like intruding weeds, into the proper pot. Thanks for being so vigilant and picking up on our wayward ways. - George
Moved to appropriate topic.
Ok, accuse me of being a bit slow. To others this may be Peyronies Disease 101. I only wish I had a lightbulb smiley.
Transforming Growth Factor - Beta 1 (TGF-B1) is a component of the immune system which I think is produced by smooth muscles under certain circumstances. One of its roles is to produce collagen. I have long known that (TFG-B1) plays a role in the development of the fibrosis we know as Peyronies Disease. As I began to learn more however, it is as though all the pieces are falling together. It is as though everything revolves around TFG-B1. This is what I think I know.
TGF-B1 is a key and possibly THE key that triggers Peyronies Disease fibrosis
Every non-surgical treatment suspected of working on Peyronies, seems to mediate (reduce) the production of TGF-B1
Pentox - thins blood and changes blood cell shape and also mediates TGF
Viagra - Oxygenates the penis with blood, reducing the TGF produced by the smooth muscles.
Now we just learned that the stretching by the VED somehow mediates TGF (not to mention mediation of TGF by any oxygenation) (lending more credibility to the VED)
Under the interesting topic "A New Theory" the writer has what seems like a well founded theory on the fibrosis of DC and Peyronies Disease based on insulin resistance. The author was articulate but seemingly in left field as far as other theories were concerned. Now, lo and behold I find out that (TGF-beta1) is a key regulator in inflammation and fibrosis in diabetes mellitus (I didn't know diabetes even involved fibrosis). Every bit of this I have learned from members directly, or from Pub Med links that members posted. Unless I am miscounting as I try to connect the dots this lends great credibility to this "New Theory" topic
TGF is at least related to Peyronies fibrosis, Heart Fibrosis, Dupuytrens Contracture fibrosis (DC), Cirrhosis of the liver fibrosis, and diabetes fibrosis.
Cirrhosis is related to DC. Peyronies is related to DC. Peyronies is related to diabetes.
Why do older men tend to get Peyronies Disease and why do frequent erections tend to help? It appears that reduction of oxygen in the penis from fewer erections causes the smooth muscles to produce TGF
I realize this has all been said more concisely and that i left out a lot of details but it increasingly looks like anything that helps Peyronies Disease does so only because it somehow mediates TGF. Anything that is known to worsen Peyronies Disease does so only because it encourages the production of TGF.
Too simplistic ???
Do Peyronies Disease docs like Levine keep careful watch for other TGF fibrosis conditions, treatment, and research ???
What can we do to make people more aware we are here and that we also need direct Peyronies Disease related research on these issues ???
Hawk,
Looks like an amazing correlation's been developed between TGF-B1 and Peyronies Disease! I'd suggest that your take your post and forward a copy of it to Levine and other top Peyronies Disease docs to a)get their opinion on the relationship between fibrosis and TGF or b)get them thinking about the relationship! I'd love to hear their opinions.
Steve
Steve,
Let me explain my hesitation to do as you suggested. First, I think TGF-B1 clearly is a key factor but the more basic problem may be what triggered its production. Apparently each fibrotic condition has its own triggers that may only produce TGF-B1 in their respective tissue (I know little about this). maybe we will never find a general TGF-B1 solution. I am also completely unsure of whether other fibrotic diseases systemically flood the body with TGF-B1 or only the effected organ such as the liver in cases of cirrhosis. Finely, I suspect it would take a doctor that was very:
Uninformed about TGF-B1
Exceptionally interested in research
And VERY VERY humble to accept anything I would point out or suggest.
As I learn more I may reconsider your suggestion since it costs nothing but rejection and I am highly experienced at dealing with that. :D
It seems clear there is a connection. But, the actual chain of cause-and-effect may be so complex - and TGF-B1 may play so many roles in our biochemistry - that a way to manage this connection to our benefit may be far off. We all realize it's unlikely that we'll really solve this problem by reading abstracts on the net. BUT - if we cast a wide net, and monitor what's being done with related fibrotic conditions - we may eventually hear about something that works, long before it would be formally adopted by the urological 'community'.
Hawk,
Great summery!
J,
Couldn't agree more
One point I want to make is our comments here may actually influence the research community. I cannot imagine researchers do not peruse this site from time to time. What we talk about must be considered by the reader, even if it is only informally. I'm not giving our site too much credit. However, we are a respectable forum with a significant web presence (THANKS HAWK). Don't think we may not have at least some impact.
J,
I always carefully read your posts because I can count on you for sound analytical comments.
Quote from: j on August 05, 2007, 02:46:14 PM
It seems clear there is a connection. But, the actual chain of cause-and-effect may be so complex - and TGF-B1 may play so many roles in our biochemistry - that a way to manage this connection to our benefit may be far off.
I completely agree with this statement and I agree that it is only a small piece of the puzzle. I also would be surprised if researches of Peyronies Disease and/or Peyronies Disease experienced urologists have not put all of this together before (although not real surprised).
I do scratch my head at the "speculation" part of your subject line. I would have
no pause at terms like "too simplistic", "incomplete", "shallow", but I can find no place it the post that I made a statement that is not pretty well established beyond the point of speculation. If so, I want to correct it. I may be a little over enthusiastic because a light (however dim) just clicked on. :D
I did qualify a couple statements that have not been demonstrated beyond speculation with terms like "appears"
Hawk, if you were speaking at a scientifc conference and laid out your case for TGF-B1, I t think there would be a lot of nodding but the term 'speculation' would still be heard. From a lay person's point of view, there's a lot of solid evidence and the connection seems beyond question; in a formal academic setting I think the idea would still be termed "speculative" until proven by experiment.
J, I think if I were to speak at a scientific conference that there would be a tar and feathering going on ;D
I think if you spoke at a urological convention, there would be a lot of embarassed silence as doctors realized how little they know about this condition that they probably see every week, compared to how much one can learn with a couple hours of Googling.
Hi guys...
just a quick note...I found one description for Vitamin E in the Slovakian
Database of Drugs and was very suprised that they admit Vit E as a
therapy for Induration Penis Plastica, also they say how much of it a man
must take to treat it :) ...even there is no approved clinical study for it, you know..
Here is the link if you want to look:
http://www.sukl.sk/buxus/docs/download/vitamin_e_100_200_400_cps_spc.pdf
if it doesnt work, try this one
http://www.sukl.sk/sk/pomocne-stranky/detail-lieku?lie_id=52716
and click on the first hypertext below.
Its in Slovakian but on the first page there is expression "Plasticka induracia penisu" (its IPP)
in the "4.1 Therapeutic indications" chapter.
And also "Iduratio Penis Plastica" on the second page in the "4.2 Measurment and aplication"
They say, you should take 300-400 mg daily during a few weeks and then 50 mg daily during a
few months.
I will be back soon with an update of my condition. I am going to have a few appointments with
urologists soon.
But I read all new posts everyday, and its always very interesting reading. :))
R3
Developing gene therapy vectors for therapeutic uses in urology:
I take it that people have seen this already: http://www.cdrewu.edu/cosh/biomedical_sciences/mcgee.htm
If so, apologize for the repost.
McGee has worked with Gonzalez-Cadavid, who is a leader in Peyronie's research.
Tim
QuoteGene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.Davila HH, Magee TR, Vernet D, Rajfer J, Gonzalez-Cadavid NF.
Department of Urology, UCLA School of Medicine, Los Angeles, California 90095, USA.
The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (Peyronies Disease) by determining whether a plasmid expressing iNOS (piNOS) injected into a Peyronies Disease-like plaque can induce regression of the plaque. A Peyronies Disease-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the Peyronies Disease plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in Peyronies Disease is defense mechanism by the tissue against fibrosis.
PMID: 15240426 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/sites/entrezcmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15240426
It's an older paper - once again out of the lab of Gonzalez-Cadavid. See the pattern? Almost all of the original thought in this field seems to come from him and his trainees or collaborators.
Unfortunately, he's a PhD, so I can't go see him for a consultation.
Tim
Auxilium announced 2 days ago that the FDA has given them clearance to resume Phase III clinical trials of XIAFLEX for Dupuytrens. This approval came earlier than expected. Enrollment of 725 patients expected to begin within 30 days. Trials to be conducted in U.S. & Australia. As you may recall the 2006 trial was interrupted when it was discovered that some of the vials of collagenase had too much moisture in them (melt back). It is great to know that Auxilium has solved this manufacturing problem. Also, the FDA has lifted the "clinical hold" on XIAFLEX for use with Peyronie's. The next step is for out of plaque animal studies to be completed so that XIAFLEX trials for Peyronie's can begin.
Mark,
Thanks for the update, this is some positive news. I'm looking forward to seeing some more trial results sometime soon. Specifically I'm looking forward to reports with more details than we saw last time. Hopefully once good dupuytrens results come back they will finally start using xiaflex off label for peyronies disease. Keep us updated, and if anyone knows of any local trial opportunities, don't hesitate to inform us. I know before blink let us know, I put my name on a list, haven't heard anything from auxillium since then.
Comeback
As stated above if the drug is approved for another use it can be used off label for Peyronies Disease. Insurance carriers wont pay but so be it if it works. Personally I am waiting for the results of the animal studies before I rush into being a trial subject.
Just one comment. Insurance often pays for off label use. It may be because the doctor writes it up differently to make it look like it is NOT off label. If this is true I guess it would be difficult in this case unless he could declare that you have Dupuytren's Contracture of the penis. ;D
Maybe he could be creatively deceptive with the vague diagnose of Dupuytren's Contracture of one of the patient's digits. ;D
I have progressive Dupuytren's in both hands. So if and when this stuff becomes real, I'll find a hand surgeon who's using it; and when I get the treatment, I'll pull out $1,000 in small bills and ask if he'll inject me in a couple of other spots. Ok I'm kidding.
You're right - flourouracil does not work.
Hi Colleen, Do you have experience with flouroucil? Please share. :)
With a big Celtic welcome,
Liam
Is this something that could reverse payronie's?
http://www.intercytex.com/icx/products/woundcare/icxskn/
http://ir.auxilium.com/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=1050270&highlight=
Quote from: Franklins Tower on September 10, 2007, 02:03:50 PM
Is this something that could reverse payronie's?
http://www.intercytex.com/icx/products/woundcare/icxskn/
Nope.
Tim
FT, We have all been anxiously awaiting completion of the "Xiaflex" (collegenase) study. I am cautiously optimistic.
Liam
anyone know when they are planning to start the IIB studies in Peyronies Disease. Did the dog study ever happen?
FYI:
QuoteAuxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) will webcast its analyst and institutional investor meeting to be held at the Grand Hyatt Hotel, on Park Avenue at Grand Central, in New York City on Wednesday, October 17, 2007.
The event will feature a discussion of clinical data and potential future commercial opportunities for XIAFLEX(TM), the Company's lead pipeline candidate that is currently in phase III development for the treatment of Dupuytren's contracture and in phase II development for the treatment of Peyronie's disease. Participants from Auxilium will include Mr. Armando Anido, Chief Executive Officer and President, Mr. Jim Fickenscher, Chief Financial Officer, Mr. Roger Graham, Executive Vice President, Sales and Marketing, and Dr. Jyrki Mattila, Executive Vice President, Business Development, R&D, and Technical Operations. Speakers will include the following leading scientific experts in the treatment of Dupuytren's contracture and Peyronie's disease:
-- Lawrence Hurst, M.D., Professor and Chair, Chief of Hand Surgery,
Department of Orthopaedics of the Health Science Center, State University
of New York at Stony Brook
-- Gerald H. Jordan, M.D., F.A.C.S., F.A.A.P., Professor, Department of
Urology, Eastern Virginia Medical School Director, Devine Center for
Genitourinary Reconstructive Surgery, Sentara Norfolk General Hospital
The event will be held from 11:30 a.m. to 3:30 p.m. Eastern Time. To access the live web cast for the presentation, which will begin at 12:00 p.m. Eastern Time, please log on to the Company's web site at www.auxilium.com approximately 15 minutes prior to the presentation. The web cast will also be archived and available on the Company's web site approximately one hour after completion of the live web cast and will remain available for approximately 90 days after the event.
About Auxilium
Hi,
Will any one be listening to this meeting ?
I am very interested to hear what they have to say, but I will busy at work.
It's also going to be 'archived' at the company's website, and will be there for about 90 days for those of us who can't listen to it 'live'.
Check this out from Modern Marvels on The History Channel - It features Dr. Anthony Atala from Harvard aand promises to have these treatments available it 3 to 10 years.
http://www.history.com/media.do?action=clip&id=mm_hts_gene_therapy_broadband
Also on this show but not on this clip was Viagra that you rub on your penis. If this direct application methond works it my cut down or eliminate the side effects
Hawk,
Do you mean that there will be ED product that is like HEAD ON - APPLY DIRECTLY TO THE FOREHEAD?
I suppose it will be called (sorry about this): HARD ON - APPLY DIRECTLY TO THE FORESKIN ;D
Liam:
In our US TOO group we have several drug company reps that attend our meetings at various times. They even sponsor meals for us, etc. They keep us to speed on the development of new drugs for ED, prostate cancer and related men's health problems.
At least two of the companies have been or are in the process of developing, testing and getting FDA approval for a topical ED cream. MUSE (Male Urethral Suppository for Erections) is in the same family. MUSE is injected in the urethra and in a very short time an erection occurs. It does have a nasty side effect for some guys. It produces a severe burning sensation especially after intercourse, etc.
I am sure that in the near futurre, at least one of these medial producers will have a topical erection cream on the market.
OM
That's a pretty amazing clip, Hawk. I'll hope for the best but expect a lot of setbacks and problems (and a looooong time for it to become affordabile to the common man) until we get DNA-grown Peyronies Disease-free packages.
Sorry if this a bit off topic, but
Auxilium Pharmaceuticals, Inc. Completes Enrollment in Two Phase III Clinical Trials of XIAFLEX(TM) for Dupuytren's Contracture
MALVERN, PA, Dec 17, 2007 (MARKET WIRE via COMTEX News Network) -- Auxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) today announced that it has completed patient enrollment in the Company's second U.S. phase III pivotal trial (CORD I) and its Australian phase III study (CORD II) of XIAFLEX(TM) (clostridial collagenase for injection) for the treatment of Dupuytren's contracture. In accordance with the study design, all enrolled patients have received their first injection of either XIAFLEX or placebo. Due to the high level of interest from patients and physicians, the Company was able to exceed its enrollment targets in both studies, with greater than 300 patients enrolled in the CORD I and CORD II studies combined. The Company had targeted enrolling 216 patients in CORD I and 60 patients in CORD II.
Well it is not for peyronie yet, but I guess we are getting closer to a release of Xiaflex I think hope it will help us
Jan 7th 2008 from Auxilium Pharmaceuticals: to Securities & Exchange Commission: "In life stage of animal study (outside of plaque) completed 4th quarter 2007. Expect to send final report to FDA 1st half 2008. Phase IIb dose ranging study (clinical trial) expected 2d quarter 2008 pending FDA review of animal study.
Still years away.... :(
However I recently read a stock analyst's writeup on Auxilium. He said that to meet projections (stock price, earnings), they will need to market Xiaflex for Peyronie's. The Dupuytren's market alone won't do it. So there there may be strong financial incentives for them to actually finish the work on this.
Well, I was at my Uro yesterday and he said that if FDA approves, the trials could start in a couple of months. Who knows how long the trials will be and when will the final results come out, but if it is approved for DC who knows may be there will be off-label use.
BTW, I was looking at the a DC forum the other day and found a thread about it where people saying they had success with it and it restored function to their hands.
Regards,
Pal
Am I to understand that Xiaflew will not reduce curvature, but will make intercourse possible by making the plaque fexlible? Is that the idea?
Pal-31, I understand that at least one protocol for trial IIb will be 6 injections over a period of 13 weeks. Mark 501
Is there anybody reading this forum that has received any of the trial injections of Xiaflex? I'm sure all of us would be interested to hear how these individuals are doing now several months out from their treatment!
Bodoo2u,
Actually the trials they had on Xiaflex only measured the curve. They defined success as a decrease of greater than 25% of the angle of the curve. I don't think they measured other symptoms and they are probably right to focus only on the angle as it is measurable. Other parameters may be harder to measure and could get into the subjective realm.
However they did give each participant a questionair that asks about other things.
This was from a presentation I read on their web-site about the medication. It was a long presentation but very informative.
Pal
They have been measuing the size of tumors for many years. I am more than a little suspicious about the reason they are not measuring plaque size. They obviously don't hold out any hope it will destroy plaque.
As far as 25%, that is not much considering all the hype.
The questionaire to be filled out by participants in Xiaflex clinical trials will be similar to the one used when Viagra was in clinical trials. The questionaire for Viagra trials was one element considered by the FDA in making its final approval and the same applies to Xiaflex.
Liam,
I really hope it is not so. However, I also happened to stumble on a DC forum and people there was reporting good results. The Auxiliam presentation said the results showed, if I remember correctly, something like 80% say they "greatly improved" or improved. At least that tells me it is better than Verapamil which if we polled 10 people who used it we will probably find 5 that say they were worse or much worse as a result :-)
I agree the jury is still out but we can only hope ( and pray)
Pal
I have Dupuytren's and have been following that situation in detail. Xiaflex definitely works. In the trial, they simply used it to weaken the cord until it could be forcibly snapped by the MD - he literally gets a good grip on your finger and straightens it until the cord breaks, often with an audible 'pop'. There's been some soreness and bruising but nothing major. However, the treatment for Peyronies will obviously have to be a bit less direct. Multiple injections over a period of time should cause some breakup of the collagen, but who knows how much and what the effect will be. It will probably vary a lot.
Even if it works, Auxilium isn't going to produce it unless they can make what they feel is an appropriate profit. After all these years of speculation and hype, that means they intend to charge a heckuva lot of money and if they can't get it, AUXL stock - which has had a big runup - will be seen as overpriced and existing options might be underwater.
Quote from a stock analyst: "If Xiaflex is to succeed, Auxilium will need to displace surgical procedures and convince insurers to pay the same for the drug as the surgery. Surgery for Dupuytren's costs $5,000. For Peyronie's, the price is $11,000. CEO Anido figures Xiaflex would bring similar prices."
I would gladly pay $11,000 for a few injections of collagenase to fix this problem. Curious to find what others might pay ...
BTW, if you'd invested $3000 in AUXL when it sold for $8/share (not long ago), the value of your stock would now pay for your treatment.
11,000!? That stinks. I'm just out of college, that's about half of a yearly starting salary, give or take a few grand, and not considering any other expense. I wonder if the healthcare people will cover it - or, since it's useful and desirable they'll label it "experimental" and refuse to cover.
That is so disheartening. I know medical procedures are expensive, but when I read things from Auxilium that states things like "High motivated consumer base willing to pay for treatment" it just reminds me that most development is driven by accounting jackals and not medical practioners wanting to cure disease. You'd figure Auxilium, requiring much less invasive treatment than surgery and thus less skill required, would cost the patient LESS, not similar or more.
Anyway, just charging at windmills here. Let's hope insurers agree to pay. Money makes the world go 'round.
Jackp, you seem to know more about accounting than I (I'm an English Lit geek, no mathematical braincells in my head) -- if AUXL stock tanked, wouldn't that be beneficial for the poor patient? They'd try to cover the loss by selling the patented formula, perhaps? I can't beleive that they'd just let it fall into the dustbin of history if they didn't meet stock price.
I dont think we should sweat the cost yet. First lets hope it works well for Peyronies and it gets approved. As for the money, and I am totaly guessing here, I dont think it will be that much as it will prevent many people from getting the treatment and the insurance wont pay. It will make more sense for them to price it where most patients can get it and the insurance wont fight it.
Just my 0.02$
In the Phase II trials with a small number of participants almost all had at least an improvement of 25 percent in their curvature. If I remember correctly there was one guy that had a 24 percent improvement. Auxilium did NOT reveal how many participants had an improvement more than 25 percent. Future trials will have many more enrolled and give a much better idea about the degree of effectiveness.
Where do you guys find the information in Xiaflex trial results?
For those of us with active disease (and I believe that is actually most of us), my concern is that even a "fix" will be just temporary, and that the disease will return. Of course, if I was fixed for a year or two, I'd gladly take it...
Tim
Quote from: Tim468 on January 16, 2008, 07:57:09 AM
For those of us with active disease (and I believe that is actually most of us), my concern is that even a "fix" will be just temporary, and that the disease will return. Of course, if I was fixed for a year or two, I'd gladly take it...
Tim
At $11,000.00 dollars a year I would almost feel obligated to have sexual partners lined up in my hallway to assure I got my moneys worth. ;D
That figure, of course, is just a number thrown out by a CEO to reassure the board and the big investors that this grand "play" is going to pay off big.
Here's another analyst quote:
"The future of Auxilium relies heavily on the development of Xiaflex. [...] Upside to our Xiaflex forecasts could come from positive development in Peyronies Disease or Frozen Shoulder Syndrome.'We model Auxilium reaching profitability in 2011. The stock looks expensive at this level based on future earnings and the current price/sales ratio."
What this means is that financial success now depends on selling Xiaflex at a breathtakingly high price. Doing that requires a big and very expensive sales/marketing effort, with lots of wining-and-dining of decision-makers. If Auxilium ultimately can't get the insurance companies to pay, things get shaky because of all the cash being burned. Executives see stock options evaporating and demand big bonuses instead, further draining cash. The board gets nervous and replaces top people - writing out big severance checks. New "rainmakers" come in based on unrealistic projections, then bail out with golden parachutes after 9 months. Eventually - even with a viable product - there's no cash to continue, and no new investors coming in, and the lights go out. I've seen it all from the inside.
Iit might all work out, somehow. Auxilium and the big insurers may settle on some figure that allows it to happen. Or, AUXL may flame out and the rights to injectable Collagenase are sold - once again - and we start all over...
I think success depends in large part on urologists agreeing to give this product a serious try, instead of referring us across town to their HMO's surgical group, or writing prescriptions for Topical Verapamil.
J
Thanks for the insightfull information , that is a very interesting post. It is sad but I think it is true.
However, I remain optimistic in the Xiaflex case. I think this is the only drug so far that has shown consistent results. Also, it actually works for DC and other fibrotic conditions. Dr. Jordan is actually involved with these trials.
I think Auxilium is close to start making money on this so I dont think they will bail. I could be wrong on all counts, but I'd rather stay positive and hopefull which at least is good for my Peyronies Disease :-)
Thanks again,
Pal
There's nothing wrong with being optimistic. Number one, Xiaflex works against Peyronie's - that much has already been proven. Number two, the company that owns the drug is actively trying to get it to market - in contrast to countless other usefull drugs for which speculators are sitting on the rights.
Number three, this is sort of the way our world works. Many other new drugs have passed through this gantlet of greed and bureaucracy, Xiaflex might make it too.
Why would speculators sit on a drug anyway? I know this is off topic, but what would be the point of sitting on a drug and not letting it get out to market? It seems like it's the difference between projected money, which gives only imagined gains in the future - and actual money, which one makes by selling a product.
I thought that the business world was about always selling. Sell, sell, sell. Not sit on something and not sell it in the hopes that one day you can.
The price of a stock is based mostly on "expected future value". While a product is just a rainbow on the horizon, investment dollars pour in - based on nothing but hype - from investors who want in on the ground floor. A successful round of fund-raising puts a lot of money in the bank which is immediately available for salaries and bonuses. And this can go on for a long time. But when a product actually gets manufactured and sold, it's real profitability becomes known, costs are incurred and the stock may plateau - often, the gravy days are over for the guys at the top.
Sometimes the rights to a "promising new drug" are more useful as bait for investment than as the basis for a real product, which may never live up to its profitability projections. Sometimes, if a company is going under because of negative cash flow, selling a patent - rather than developing it into a product - is a quick way to raise money.
The patent on Collagenase has brought in many millions of investment dollars over the last 10 years. The trials have been on, off, on, off more times than I can recall. This time it looks like they're going to complete the trials, more than 10 years after collagenase was first used successfully on Dupuytren's..
Biospecifics Technologies Corporation has a development & license agreement with Auxilium Pharmaceuticals for clinical applications of Xiaflex in treatment of Peyronies, Dupuytrens & Adhesive Capsulitis (frozen shoulder syndrome). Auxilium has an option to acquire from Biospecifics additional licenses for treatment of cellulite & lipomas. This from Biospecifics: " Significant portion of our revenues are tied directly to the success of Auxililum commercializing Xiaflex".
From Auxilium today: Urologists have reported to Auxilium that there has been an increase of patients seeking help with peyronie's since the introduction of PDE inhibitors. They further state that approx. 475,000 men with peyronie's consult with a urologist annually. The latest estimate of the cost of Xiaflex is $l,600 per each injection. They have patent protection until 2019.
So if all those guys with Peyronie's get just one shot of Xiaflex, Auxilium grosses $760,000,000. I'm sure the investors are loving these projections. But let's wait and see what the insurance companies say.
J,
We can have fun with these numbers. For a 16 injection protocol, which showed the most result, the total $$$ would be 760 M x 16. If this number of patients is only in the US then we could probably multiply that by 100 for world wide distribution, etc...
Auxillium needs to get busy and get this thing on the market so they can start making the big bucks...
Pal
Pal-3l, There is no 16 injection protocol. Previous trials for peyronie's had as many as 9 injections. The next trials, Phase IIb is a dosage trial in an attempt to reduce the required number of injections down to 6. In trials for Dupuytrens some patients only needed 1 injection per joint & some needed 2 but not more than 3. I suspect that not all cases of peyronie's will require the same amount of injections for a good outcome. Also I don't think that all men with peyronie's will be good candidates for this treatment. Auxilium is promoting the idea that they will become a billion dollar business.
Auxilium's investor pitch is probably something like this:
1. The current treatment for Peyronie's is surgery.
2. Insurance companies will pay for our treatment if it costs a little less than surgery.
3. Surgery costs $11,000.
4. Success is defined as a measureable reduction in curve, say 10%
5. Our product is "successful" with an average of 6 injections.
6. 6 x $1600 = $9600
This leaves $1400 for 6 visits to the urologist.
It's all hype at this point. The insurance companies may bring things into reality, or shoot down this product entirely. Maybe a long slow 'trial' period including pointless and unscientific self-evaulation of "customer satisfaction". Or maybe it works great and within a couple of years, a lot of us are much better off. Life is unpredictable.
Mark,
I dont know where I got the 16 injections number from. I must have been half asleep. The number that got the most success was what they call group B which had 3 series of 3 injections so a total of 9.
Just from reading the results of the trials I am optimistic. Hopefully it will work for us. I am an average guy financially, but I would not mind paying the money if it worked as they claim.
Once it gets to market will find out (soon enough hopefully)
Pal
If it works, believe me, we will all work all the angles to get it covered by insurance. For my insurance, I think that if I have a lot of pain with erections, surgery is covered, otherwise it's just "cosmetic".
Already, I think I feel an ache....
Tim
;D Oh the Pain...The severe ED...The Loss of Appetite...The Dandruff...Anything to get Insurance to pay for it!!! ::)
Mental health coverage is politically hot - insurers are under pressure. So - would it be more cost-effective to send me to a therapist until I accept that life with a bent peter isn't all that bad - or to pay 11K and maybe fix the problem?
Actually, the therapy is not going to be effective if I know there's an actual treatment.
How do you guys feel about being part of a clinical trial of Xiaflex if the cost of the medicine to you is zero? Would you be willing to pay for travel & hotel expenses if trials were held in another city? What if there was a possibility that you might receive a placebo instead of xiaflex? I have been weighing these questions and can't quite decide. Does an "open label" trial mean that there are no placebos involved?
Mark,
I am guessing that "open label" means you are getting the the real deal. Double blind usually means , I am guessing again, you dont know if you are getting placebo or the real stuff.
Are you being asked to participate in the trials ?
Thanks,
Pal
mark501, my understanding also is that no one will get a placebo.
I don't think you can ethically make multiple injections into a man's penis with a placebo. You could possibly use a control like Verapamil, but I am not suggesting that they intend to use such a control.
I don't mean to beat a dead horse, but since the discussion was still revolving around money:
Is there any chance that, a few years out of the gate, Auxilium gets that initial "rush" of men waiting for Xiaflex and then drops thier price to lure in the less drastic cases of Peyronies Disease, the one's guys want to correct but isn't causing them ED or anything?
Similarly, what are the odds of insurers picking this up? I admit I know little to nothing of how they work, and given that I'm fresh out of college I'd be more likely to stumble on a chest of gold dubloons to pay for Xiaflex than find an employer willing to give me premium benfits. Don't insurers label anything they want as "new" or "experimental" and deny payments for them?
My only reassurance here is that insurers pay for Viagra, which isn't life-threatening but apparently important enough to warrant coverage. It seems that if getting hard is covered, straightening your penis would be an easy choice to cover.
Quote from: ocelotDon't insurers label anything they want as "new" or "experimental" and deny payments for them?
My only reassurance here is that insurers pay for Viagra, which isn't life-threatening but apparently important enough to warrant coverage. It seems that if getting hard is covered, straightening your penis would be an easy choice to cover.
I will comment only on your this quote. I have Blue Cross and it does NOT cover Viagra. I do get some kind of "discount that lowers the price somewhat but I still pay about $11.00 a pill for 100mg. Also, insurance companies do not just get to label anything they want as experimental. There are guidelines that establish what is usual and customary in the way of charges and to establish what is or is not accepted as standard treatment.
ocelot556, don't let all this cynical pseudo-analysis get you down.
Any company starts out crowing about they'll get absolute top dollar for their whiz-bang new product, because the world will beat a path to their door. And then they encounter reality. If Xiaflex really works, and their really are that many guys with Peyronies, market forces will work to extract every possible dollar from everyone who might possibly pay. Sometimes that means a product initially sells for a very high price to people who are standing in line with fistfulls of money; and eventually, the price sinks down and deals are worked out so they can collect money from the rest of us too.
Remember how fast the iPhone went from $600 to $400?
Hawk
I am a retiered county government employee. The powers that be have reneged on a verbal agreement and put us on Medicare Part D with a supplement.
None of the ED drugs are now covered and we have to pay full price.
Another case of the government taking money out of the pocket of retires to pay for there mistakes.
Jackp
Yeah, you're right. But since it's my opinion that a bad and barely-documented side effect from another drug caused my Peyronies Disease in the first place, and my own experience working for medical device companies, it hasn't left me with much love or trust of corporations in general when they're in the business of medicine. And Peyronies Disease is enough to make anyone a cynic! Hah.
Quote from: ReutersWASHINGTON, Feb 15 (Reuters) - U.S. health regulators on Friday issued proposed guidelines that would make it easier for pharmaceutical companies to advise doctors about unapproved uses for their drugs.
http://www.reuters.com/article/companyNews/idUSN1560771720080215 (http://www.reuters.com/article/companyNews/idUSN1560771720080215)
Hi,
Can someone recomend a doctor in the Chicago area, other than Dr Levine.
I would like to locate a doctor who is working with the new Auxillum Xiaflex treatment.
In the discussion form here: Peyronie's Advocacy Group - Awareness/Advocacy/Activism > Auxilium Follow Up
someone mentioned twenty doctors are participating in the Auxilium trials. Does someone have a list of who those
twenty doctors are?
Thank you
JXYZ
Jxyz,
I admittedly do not follow Xiaflex that closely, but I know of no doctors currently part of a trail of xiaflex for Peyronies Disease. If there were any in the Chicago area, I think it is safe to say Dr. Levine would be one of them both due to his medical emphasis and his loose association with Auxilliam.
Does anyone know whether the gene therapy being tested by Mehlman and Co. in New York would apply to cases of ed that might be caused by diffuse fibrosis or cavernosal scarring?
Since I do not see this study posted anywhere, I am going to throw it out to you all now for any information you might glean from it:
Quote from: PubMedThe use of intralesional clostridial collagenase injection therapy for Peyronie's disease: a prospective, single-center, non-placebo-controlled study.
Jordan GH.
Department of Urology, Eastern Virginia Medical School, Norfolk, VA, USA. ghjordan@sentara.com
INTRODUCTION: Peyronie's disease afflicts at least 3% of sexually active men over the age of 30. Many pharmacologic therapies have been tried, but to date, no systemic or local therapy has been proven to provide predictable and lasting results. AIM: This study was designed to assess the efficacy and safety of intralesional clostridial collagenase injection therapy in a series of patients with Peyronie's disease. METHODS: Twenty-five patients aged 21-75 years who were referred to a single institution with a well-defined Peyronie's disease plaque were treated with three intralesional injections of clostridial collagenase 10,000 units in a small volume (0.25 cm(3) per injection) administered over 7-10 days, with a repeat treatment (i.e., three injections of collagenase 10,000 units/25 cm(3) injection over 7-10 days) at 3 months. Primary efficacy measures were changes from baseline in the deviation angle and plaque size. Secondary efficacy end points were patient responses to a Peyronie's disease questionnaire and improvement according to the investigators' global evaluation of change. MAIN OUTCOME MEASURE: The primary efficacy measures were change in deviation angle and change in plaque size. Secondary end points were patient questionnaire responses and improvement according to the investigators' global evaluation of change. RESULTS: Significant decreases from baseline were achieved in the mean deviation angle at months 3 (P = 0.0001) and 6 (P = 0.0012), plaque width at months 3 (P = 0.0052), 6 (P = 0.0239), and 9 (P = 0.0484), and plaque length at months 3 (P = 0.0018) and 6 (P = 0.0483). More than 50% of patients in this series considered themselves "very much improved" or "much improved" at all time points in the study, and the drug was generally well tolerated. CONCLUSION: The benefits of intralesional clostridial collagenase injections in this trial lend support to prior studies supporting its use in the management of Peyronie's disease. A double-blind, placebo-controlled study is currently under development.
PMID: 18173766 [PubMed - in process]
Can't get hold of the whole thing. It is also another unblinded study, but supports the notion that breaking up scar made of excessive or abnormal collagen will relax the contraction. If one had a palpable plaque, I think it sounds very promising (and clostridial collegenase is not a "new" drug, and coult herefore be studied but not have to go through the same FDA hoops as a new drug).
Tim
George999, that study you posted I believe is the abstract for the Phase II study done by Auxilium for Xiaflex, right?
With regards to Xiaflex, I was thinking that one way in which this forum might be helpful to its members would be for everyone who sees a urologist to ask them (the urologists) whether they are familiar with the clostridial collagenase studies and if they will be using this drug off-label for peyronies once it is approved for dupuytren's. It may cause them to research it more and possibly incorporate this therapy into their practice if they feel it safe and efficacious. Everything I have read thus far has been positive and although no definitive studies have been completed they are in the works. Although it will be no magic bullet, it seems that this will be the best option yet for non-surgical management of this disease.
So, next time any of you go to your urologist ask about Xiaflex (clostridial collagenase) and see what they have heard and if they plan to be using that off-label because it is becoming more and more acceptable to do so when it seems appropriate. I would guess that at least a handful of urologists across the country will be doing so and I'm sure many of us will be lining up for an appointment! It's not to early to begin to discuss this because the data from the dupuytren's study should be out shortly and they anticipate applying for a patent I believe by this time next year.
roadblock
Ah, I think that Roadblock has it right. This is Xiaflex.
Tim
I might be beating a dead horse here, but does anyone know if there are interferon studies going on now? I've seen a few promising summaries about it's interaction with Peyronies Disease, but apart from the fact that Dr. House is always giving his patients interferon on TV, I don't know a single thing about it! It seems like this is a solution that encourages the production of collagenase in the body, and yet I don't know of anyone who's received it as a treatment. Anyone know anything about this?
Synvista is continuing its work on Alagebrium which is apparently in Stage III trials. This drug is the "only A.G.E. Crosslink Breaker in advanced human testing". I believe this drug holds great promise for Peyronie's patients:
Quote from: Synvista R+D PipelineSynvista's clinical program on treating diseases associated with aging and diabetes is focused on alagebrium, a first-in-class A.G.E. Crosslink Breaker. It has been demonstrated that the formation of A.G.E. Crosslinks is a process that results in irreversible tissue damage associated with enhanced inflammation, deposition of collagen, the major structural protein in the body, and a diminished function of many tissues and organs. Alagebrium is the most advanced agent in a new class of compounds thought to chemically "break" A.G.E. crosslinks, thereby restoring more normal function to organs and tissues that have lost flexibility or function as a result of the crosslinks or the consequent tissue alterations induced by inflammation and scarring. By cleaving the pathological bonds that cause tissues, organs and vessels to stiffen and lose function over time, alagebrium has demonstrated the ability to reverse certain age-related and diabetes-related conditions. A.G.E.s also are known to upregulate various inflammatory and matrix producing cytokines. These signaling molecules are known to modulate the body's response to injury and inflammation and are responsible for both healing and scarring of tissues. As a composite, these cytokines induce pathologic alterations in tissues and organs resulting in a loss of flexibility or function. The deposition of excess collagen matrix protein in the heart results in stiffness of the ventricles or pumping chambers of the heart leading to diastolic dysfunction and chronic heart failure. Similar deposition of matrix proteins in the kidney results in scarring of the kidney with leakage of protein into the urine. Similar alterations are known to occur in many organs including the eye, resulting in visual impairment that is provoked by aging or elevated glucose in diabetes.
Alagebrium efficacy data are consistent across species. Studies in animal models in numerous laboratories around the world have demonstrated rapid reversal of impaired cardiac, vascular, renal, and other systemic functions with alagebrium. Alagebrium is being evaluated in various pre-clinical models to assess its safety and potential in a number of other disease states, including atherosclerosis, vascular calcification, peritoneal dialysis, osteoarthritis, arterial remodeling, forensic DNA identification, ischemic induced neovascularization, effects on renal function in response to oxidative stress, glaucoma, acute macular degeneration, erectile dysfunction and Alzheimer's disease, among others.
Synvista R+D Pipeline (http://www.alteon.com/cross1.htm)
More information can be found in their February 2008 overview document:
Synvista February Overview (PDF Document) (http://media.corporate-ir.net/media_files/irol/10/100218/Synvista%20February%20Overview%20Final%20-%202008-02-27.pdf)
Research on this product IS ONGOING globally and is uniformly PROMISING!
Advanced glycation end-products and arterial stiffness in hypertension. Mar 2007 (http://www.ncbi.nlm.nih.gov/pubmed/17324733?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Quote from: PubMedThis brief review discusses the formation of AGEs, their role in mediating cardiovascular injury, as well as the results of experimental and clinical studies involving alagebrium.
Cross-link breakers as a new therapeutic approach to cardiovascular disease. Nov 2007 (http://www.ncbi.nlm.nih.gov/pubmed/17956231?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Quote from: PubMedWe aimed to evaluate the role of AGEs on duodenal nNOS expression and the effects of aminoguanidine (a drug that prevents AGE formation) and ALT-711 (AGE cross-link breaker) in experimental diabetes.
Inhibitors of advanced glycation end-products prevent loss of enteric neuronal nitric oxide synthase in diabetic rats. Mar 2008 (http://www.ncbi.nlm.nih.gov/pubmed/17971026?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
For those interested in further reading on the subject:
Background: Glycation and Crosslinking Proteins (http://www.legendarypharma.com/glycation.html)
Wow...sounds too good to be true. One thing I didn't see, though, was much in the way of current, ongoing trials. Is it dead in the water? Surely with the broad spectrum of possible applications for this drug someone would pick up the ball and run with it?? At least we have Alagebrium and Xiaflex on the horizon to give us something to feel hopeful about!
Addendum: I take that back...looking a bit more closely at the info on their website it appears that they are going forth with two Phase 2 trials that should produce data by sometime in 2009. So, probably looking at 2012 or so?
http://en.wikipedia.org/wiki/Alagebrium
...It's wikipedia, sure, but it says here that the company that picked Alagebrium up isn't going to be developing the drug for economic/pharmaceutical reasons. I hope this isn't true - since the last line essentially conveys "This molecule is easy to replicate and therefore not cost-effective, therefore it will never be released!" or something. Maybe I'm misreading in a pessimistic way.
I think it is helpful to look at their 10K which is a form that they must file with federal regulators and disclose. Prepare to be blown away!
Quote from: Sysvista 10K filed 03/31/08Alagebrium chloride or alagebrium (formerly ALT-711), is an Advanced Glycation End-product Crosslink Breaker being developed for diastolic heart failure ("DHF"). To date, alagebrium has demonstrated potential efficacy in two Phase 2 clinical trials in heart failure, as well as in animal models of heart failure, nephropathy, hypertension and erectile dysfunction ("ED"). The compound has been tested in approximately 1,000 patients, which represents a sizeable human safety database. Our goal is to develop alagebrium in DHF and nephropathy. These diseases represent a rapidly growing market of unmet medical needs, and are particularly common among diabetic patients. ... The data from one Phase 2 clinical study, presented at the American Heart Association ("AHA") meeting in November 2005, demonstrated the ability of alagebrium to improve overall cardiac function, including measures of diastolic and endothelial function. In this study, alagebrium also demonstrated the ability to significantly reduce left ventricular mass. In November 2007, a 100-patient, placebo-controlled, two-arm study called BENEFICIAL (Double-blind, placebo-controlled, randomized trial evaluating the efficacy and safety of alagebrium) began patient enrollment to evaluate the efficacy and safety of alagebrium in patients with chronic heart failure. We expect to report initial results from this study in the second quarter of 2009. ... In July 2006, we announced that the Juvenile Diabetes Research Foundation ("JDRF") awarded a research grant to one of our independent researchers, Mark Cooper, M.D., Ph.D., Professor at the Baker Heart Research Institute, Melbourne, Australia. This grant will fund a multinational Phase 2 clinical study of alagebrium on renal function in patients with type 1 diabetes and microalbuminuria. Alagebrium will be tested for its ability to reverse kidney damage caused by diabetes, and to reverse the protein excretion which is characteristic of diabetic nephropathy. Dr. Cooper has demonstrated promising preclinical results with alagebrium in diabetic kidney disease. We expect to enroll patients in this study beginning in the first quarter of 2009 and results may be available approximately 30 months following enrollment of the first patient. ... In addition to these pipeline products, we have identified compounds in multiple chemical classes of Glutathione Peroxidase Mimetics and A.G.E. Crosslink Breakers and A.G.E. Formation Inhibitors that may warrant further evaluation and potential development. ... A.G.E. Crosslink Breakers have the potential to treat a number of medical disorders where loss of flexibility or elasticity leads to a loss in function. Alagebrium has demonstrated the ability to reverse tissue damage and restore function to the cardiovascular system in Phase 2 clinical studies in cardiovascular distensibility and DHF. Additionally, we are evaluating the development of several compounds in the breaker class for other indications where A.G.E. crosslinking leads to abnormal function. ... We have identified several potential chemical classes of A.G.E. Crosslink Breakers, and have an extensive library of compounds. ... The majority of our patents and patent applications are in the following three areas: there are 146 issued patents and 45 pending applications in the United States and world-wide, related to A.G.E. crosslink breakers.
Note that research IS ONGOING! Also note that alternative non-profit funding sources are being tapped. In addition note that they have more potential AGE related products in the wings. The full 10K is posted here (http://phx.corporate-ir.net/phoenix.zhtml?c=100218&p=irol-SECText&TEXT=aHR0cDovL2NjYm4uMTBrd2l6YXJkLmNvbS94bWwvZmlsaW5nLnhtbD9yZXBvPXRlbmsmaXBhZ2U9NTU3MTU5NiZhdHRhY2g9T04%3d). There is plenty of information included which gives a much better picture than the brief and misleading Wikipedia entry. This company is very much alive, active, and dedicated to delivering their product. They currently have $26M on hand having spent $260+M since 1987 or so. So far they have profited nothing. But this is the nature of the industry. They are continuing to raise the money and are continuing to move alagebrium through the necessary regulatory hopes. They are not there yet but they are moving along, none the less. These compounds are EXTREMELY promising and one way or another they will find their way into the market place. So chill out! - George
If it can kill cancer, could the same methodology also knock out plaque?
(The Kanzius Machine) (http://www.cbsnews.com/stories/2008/04/10/60minutes/main4006951.shtml?source=RSS&attr=HOME_4006951)
When I saw it on TV I thought the same thing. We have to identify a way to get the metallic compounds into the plaque, which is really touch material with low blood flow. It would require getting antibodies to attach to plaque specifically, and "flip" the "nano-bots" of metal into the cells. No easy task.
Tim
For the doubters out there, here is even more evidence that SynVista is serious about Alagebrium chloride AGE-Breaker.
Current Trial (note the date!) (http://clinicaltrials.gov/ct2/show/NCT00662116?intr=%22Placebo%22&rcv_s=04%2F10%2F2008&count=1000)
Hi everyone!
I was reading about the clinical development and trial of AA4500 (collagenase) of Auxilium labor (the last new)... Someone knows how is the progress of the trial? I read that AA4500 will be able in the market in 2008/2009... So, i think that they are having sucess in tratament (Can we have hope? :D)... And this forecast is to Europe, after this the USA, and someday here...
I don't have find any research about Peyronie... Really exists an interest
of the labors to find a cure? :(
George: I didn't understand all about Algebrium.. It's just for ED or improve Peyronies to? (curvature and plaque)
Whether it is ED or Peyronies, the root of the problem is tissue fibrosis. In the case of Peyronies, it is fibrosis of the Tunica Albuginea. In the case of ED, it is more likely to be Vascular Fibrosis. Alagebrium treats both problems. Its first use will likely be for Systolic Hypertension which is caused by Arterial Fibrosis. Alagebrium Chloride is a drug that acts at the molecular level to treat virtually all forms of tissue fibrosis from Cataracts to Cirrhosis of the Liver and perhaps even Alzheimers. It works by dissolving the abnormal molecular bonds at a systemic level. It is a very promising substance that I believe has a great future. Multiple Phase II trials have already been done and all have been successful. - George
Like a man drowning in the ocean we will reach for a piece of straw to help us stay afloat. If this " Alagebrium Chloride" is great stuff I don't suppose a man
can stop at the local chemical supply house and pick some up. It's side effect
is probably worse than Peyronies ( if that is possible ). George how can I place
my order?
The thought crossed my mine about the drug testing. If half of the men take
a "placebo" and the drug works, what about the poor B@@@ards that took the
empty bullets?? Do they get the real thing later?
If I sound a little irritated it is sometimes hard to live with a boomerang.
Musicman, Its out there, but I certainly wouldn't recommend anyone buy it at this point. The reason is that I am not sure that one could trust the supplier AND that it would be difficult to work out the right dosage. I thoroughly understand your frustration, but there are some legit reasons why drugs are tested the way they are. Anyone participating in a study who receives a placebo instead of a drug that later proves effective can have access to that drug just like anyone else when it is approved. I have a lot of confidence in the effectiveness of this particular drug from what I have read and hopefully it gets approved for SOMETHING soon. At that point the trick will be convincing our uros to prescribe it for an off-label use. On the other hand, some innovative uro like Dr. Lue could pick up on it and make it available on a quasi research basis. Another important point is that this drug is just the first of a number of new drugs with the same mode of action that will be moving through clinical testing in the days ahead. Anyone of them could end up being a (the first) really good Peyronies treatment. Until then, the most effect treatment in my estimation is probably the VED. It is certainly the only treatment that offers relatively quick results. - George
George I follow your way of thinking very well but I am sure a man
that is dying of a disease wants a cure Right Now! My thinking is that
if a person wastes 2 years on the placebo he is never going to make that
2 years back. I am not getting any younger and sooner is better.
Musicman
Synvista has announced that its Alagebrium trial is now underway with completion expected within the next 18 months or so:
Synvista Initiates Phase II Heart Failure Study (http://www.redorbit.com/news/health/1385230/synvista_initiates_phase_ii_heart_failure_study/)
Synvista Therapeutics Announces Initiation of the BREAK Study of Alagebrium for Diastolic Heart Failure (http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/05-13-2008/0004812243&EDATE=)
George, you're the dogs bollocks as they say for keeping on top of these things. Thank you for your effort, it's always a glimmer of hope in what is generally a hopeless affair.
I've been doing a little reading into Synvista, as well, after following the links you previously put on this forum - and noticed that in some of the writeups of alagebrium it says that it only breaks one of two kinds of AGE fibrosis. I can't recall what the two types were, but do you think this is a potential cure? They certainly seem to discuss it that way vis a vie arterial plaque, but I can't be sure how much of that is hype versus the actual results.
Similarly, would the AGE breaker compounds really do that much for established plaque in the tunica? Obviously this is fledgling stuff and being employed for more life-threatening diseases, but the results in the ED reports are heartening. Wouldn't alagebrium also reverse a number of other problems in the body, like accumulating but-not-yet-dangerous artertial plaque, poor circulation, wrinkles, et al?
I'm surprised if (as they claim in a lot of the AGE breaker literature) most issues of aging are caused by glycation endproducts, that there isn't millions more in this research. Maybe I'm not grasping it, but it seems like this would be the "golden ticket" for any company, if it can reverse the byproducts of the aging process, specifically superficial ones like skin quality...
Quote from: ocelot556 on May 22, 2008, 03:18:16 AMI've been doing a little reading into Synvista, as well, after following the links you previously put on this forum - and noticed that in some of the writeups of alagebrium it says that it only breaks one of two kinds of AGE fibrosis.
There are two major types of AGEs. Both (plus lesser types) can be inhibited by currently available products. As of now, only one type can be broken by Alagebrium and other products in the drug pipeline. The search is on for substances that can break the other major type at this point. There is LOTS of work going into this behind the scenes by some major venture capital pharmaceutical organizations.
Quote from: ocelot556 on May 22, 2008, 03:18:16 AMI can't recall what the two types were, but do you think this is a potential cure? They certainly seem to discuss it that way vis a vie arterial plaque, but I can't be sure how much of that is hype versus the actual results.
If you break half the crosslinks, you get a LOT of elasticity back. Enough so that you wouldn't be worrying a lot about the other 50%. So I am not sure I would use the word cure in the sense of ending up as pure as a baby. But I suspect it will be a functional cure.
Quote from: ocelot556 on May 22, 2008, 03:18:16 AMSimilarly, would the AGE breaker compounds really do that much for established plaque in the tunica? Obviously this is fledgling stuff and being employed for more life-threatening diseases, but the results in the ED reports are heartening. Wouldn't alagebrium also reverse a number of other problems in the body, like accumulating but-not-yet-dangerous artertial plaque, poor circulation, wrinkles, et al?
That is the exciting part. This new emerging class of drugs has the potential to positively impact the whole body. And that is something that is being noted in the studies. Participants are realizing that other things are getting fixed besides what this drug is targeted for. But one thing you have to understand is that it is dependent on things like blood flow in terms of efficacy in clearing out AGEs. The tunica has notoriously poor blood supply. This means that once again we are looking at a long term project. On the other hand, Synvista is targeting the Aorta simply because it has notoriously robust blood supply and can be repaired rather quickly. So this is the fastest route to get this drug through the FDA. From there, they should finally have a food chain to feed further research and approved uses.
Quote from: ocelot556 on May 22, 2008, 03:18:16 AMI'm surprised if (as they claim in a lot of the AGE breaker literature) most issues of aging are caused by glycation endproducts, that there isn't millions more in this research. Maybe I'm not grasping it, but it seems like this would be the "golden ticket" for any company, if it can reverse the byproducts of the aging process, specifically superficial ones like skin quality...
At this point it is mostly venture capital companies. Thats the way it ALWAYS is with new therapies. But once it gets approved, watch for Synvista to get snapped up by one of the big guys. There are two things at play here. 1) The big companies ALREADY have blockbuster products and they don't like to take risks on new approaches. They prefer to build on and refine what they already have. 2) They view new approaches with some degree of fear and trepidation and are to some degree loathe to fund them. After all, can you imagine what this would mean to a number of companies current product portfolios that DEPEND on the AGE process to generate customers? So its really a two edged sword for them. But once the cat is out of the bag, watch for one of the big guys to snap this up. The choice is to be innovated out of business or to own the new killer product. They will all be looking for a way to survive once this is out the door. There will likely be a feeding frenzy of buyouts of all the little VC outfits that our making headway in this arena. - George
Quote from: HealthDayFRIDAY, May 23 (HealthDay News) -- Patients with a progressive fibrosis of the lungs that's fatal within a few years of diagnosis may finally have some reason for hope.
Japanese researchers say daily use of the drug pirfenidone improved the lung function and lengthened the survival of patients with the illness, called idiopathic pulmonary fibrosis (IPF).
Drug for Deadly Lung Disease Shows Promise (http://www.healthday.com/Article.asp?AID=615764)
- George
QuoteI was diagnosed with Dupuytrens about 10 years ago and had a very successful palmar fasciectomy about 7 years ago. Nonetheless, the nodules and bands continued to develop in other parts of both hands. Two years ago, I started treatment in a clinical study of an investigational drug, pirfenidone - an anti-fibrotic which has been successful in treating pulmonary fibrosis. The purpose of my study was to investigate the drug for treatment of radiation-induced fibrosis. (I was treated with radiation and chemotherapy six years ago for throat cancer). The drug helped a lot with my swallowing but I also noted a distinct improvement in the Dupuytrens. It used to be painful for me to tightly grasp certain objects - no more. I saw my hand surgeon last week and he measured my range of motion in all fingers as at or within 2% of normal. On some fingers, the bands have disappeared and on others, they have significantly reduced. So, something is going on and I think it is the pirfenidone.
There were less than 10 people in my study and there are not that many people with pulmonary fibrosis so I might be the only person taking this drug who happened to also have Dupuytrens.
I have emailed the manufacturer of the drug to make sure that they know about my experience. I am not sure what to do next but I would like to get some organization to press the manufacturer to conduct a study of this drug on DC victims. BTW, the only side effect I experienced was some stomach upset which Prilosec counteracted and some fatigue during the first few months of the study.
Source: http://www.biospecifics.com/DNForum/default.aspx?f=5&m=2104 - Post from way back in 2004 . I have no way of ascertaining it's validity, but it's very interesting and hold potential promise, no?
Edit - Just did a search and found that this had been posted here a couple of years back. Feel free to delete it if you wish.
newguy:
If you will go to the Child Boards topic you will find a thread that contains quite a number of posts brought to this forum from the Biospecific forum when this one was started. It contains the "best posts" from the Biospecific forum made by bone fide people.
This forum resulted because the man who started it was totally fed up with the way that forum was run. That forum did not require registration, no I.D.s or passwords to join. It was a disaster so for all practical purposes it became useless.
Old Man
It just gets better! Here is yet another company developing anti-Glycation drugs:
Quote from: Philadelphia Business JournalEarlier in the company's history, Tobia was in a lab where the company was conducting animal studies related to 3DG and diabetes.
"I picked up one of the mice," she said. "Don't ask my why I did it, but right away I could feel the difference in the skin of the animal being treated. There was a measurable difference in the skin elasticity of the animals being given the drug and those who didn't get any."
Dynamis discovered 3DG causes inflammation, loss of collagen, disabling of collagen and other factors that contribute to skin aging.
Dynamis finds compounds that may slow aging process (http://philadelphia.bizjournals.com/philadelphia/stories/2008/05/26/story8.html?b=1211774400%5E1639402)
- George
Hi George,
I wrote a long piece on Pirfenidone a while back for those who are trying to understand it's mechanisms.
https://www.peyroniesforum.net/index.php/topic,35.msg6411.html#msg6411
The anecdotal evidence regarding DC is very interesting - and precisely how ideas promulgate. What is awful is how reports like this do NOT lead to clinical trials like they should.
Also, don't forget that Intermune had to be sued by sufferers of Indiopathic Pulmonary Fibrosis (IPF) to get the studies back up and running. I am not sure why the Japanese group ended up publishing first. It was interesting to learn that more people die of IPF than do from breast cancer every year, yet no-one seems to know anything about it.
Tim
Quote from: Tim468 on May 25, 2008, 01:40:15 PMWhat is awful is how reports like this do NOT lead to clinical trials like they should.
Hmmm ... I wonder if it has something to do with $$$?
Lipoxysan is another promising treatment that has yet to get off the ground after nearly three years since promising trial results were reported. I really suspect that the fact that the pharmaceutical execs are aware that these treatments against Glycation and its effects would severely compromise the performance some of their current star products has something to do with the decision to relegate these candidates to the round file as quietly as possible. Maintenance drugs have a far superior profit profile as compared to curative treatments so it is not surprising that these companies tend to focus their R+D money on maintenance drugs. - George
Well the FDA is finally taking another huge step forward. They are experimenting with fast tracking medications that target the terminally ill and allowing them to skip the safety testing normally required. DUH! Finally common sense is prevailing. When you've got someone with months to live, you worry about the safety of a promising experimental treatment? I don't think so. For those of you who are younger and probably not aware, the medical establishment used to worry about the safety of administering appropriate pain relievers to the terminally ill. No kidding. And there were many medical professionals that used to obsess over the possibility that there terminally ill patients might become 'addicted' if they didn't restrict pain relief medication. Thank God we finally got over that one. Why is this important to us a Peyronies sufferers? Simply because this means that finally the medical establishment, including the regulators is starting to pay attention. AND there are indications that they are finally questioning why promising therapies are languishing because they involve generic commodities (like alagebrium chloride and green tea) and thus provide no financial incentive for trials. If we could finally get over that hill and direct public funding toward those candidates the impact on public health would be immense and we would all benefit. Why green tea? Initial research is showing that green tea MAY PREVENT Alzheimer's and other fibrotic syndromes BUT are frustrated because NO MONEY is available for further research because their is no profit angle. Hopefully the trend continues and further enlightened changes are made in the way things get done in medicine. - George
I am new to this forum, but have suffered from Peyronies Disease for a while. George999 mention VED as a good treatment. What does this acronym stand for?
thanks
alfapd:
VED stands for Vacuum Erection Device. They have been used successfully for a number of Peyronies Disease sufferers. It was designed originally for erectile dysfunction. Later, it was found out that with a special regimen of exercises that it would help with Peyronies Disease symptoms.
There is a special thread on the forum devoted to that title, VED, etc. So check it out. Also, in the Child Boards topic on the Home Page, there is many posts compiled into one place so that new guys can learn as much as possible about VEDs and their use. So check out that thread too.
Let us know if we can help in any way. Welcome to the forum!!!!
Old Man
The trend of the AUXL share price is encouraging for Peyronies Disease sufferers. It just matched it 52-week high (contrast that with the DJIA). The only product in AUXL's portfolio with promise is the collagenase, trade name Xiaflex. Even the analysts believe in this drug, suggesting it will make Auxilium profitable by 2010.
As a secondary benefit, Peyronies disease will gather new attention after Xiaflex comes market. Men will be coming out of the woodwork for treatment and that may inspire other pharma to invest in Peyronies treatment.
In the end I believe that we'll combine treatments like collagenase injections to clear existing plaque, pentox to stave off oncoming bouts of inflamation, and traction/vacuum devices to prevent and correct deformity.
Peyronies Disease sux, but this is the best time in history to ever suffer from this affliction because we might be within a few short years of effective treatment. Don't give up!
couldbeworse - I definitely agree that peyronie's will be getting more attention in future. I've spoken with very educated professionals in the medical field who are unaware of peyronie's. It's quite shocking really. The development of drugs with potential to treat peyronie's, along with other scarring based disorders will no doubt shine a light in the condition - and god only knows it won't be befiore time.
Indeed, I agree very much with the previous two posts. There is just so much coming down the R+D pipeline right now that bears promise in treating Peyronies. And, of course, this is a good thing which promises great benefits especially for those younger guys among us. My only real concern is that, since Peyronies does not occur in vacuum, but happens due to a metabolic environment that encourages its development, even a successful treatment can end in disappointment when the Peyronies returns as soon as treatment is concluded. So unless we strive to try to correct the underlying metabolic problem, a long term cure is likely to be elusive even in the presence of effective treatments. - George
This may be kind of a stupid question, but does anybody think Xiaflex could possibly be described off-label? Seems like no, because I mean often pills are prescribed off-label, but that is because they have tests showing that it is relatively safe to take the pill. Whereas with Xiaflex, you wouldn't be injecting your hand like the on-labelers, you (or more accurately, your uro) would be injecting your penis. I can't see that ANY urologist would be willing to take that risk and start injecting Xiaflex off-label. I read that Aux doesn't even plan to APPLY for whatever it is to get approved for use in America until early 2009, so I'm guessing it will be at least a couple years before Xiaflex could POTENTIALLY be prescribed for Peyronie's treatment given their current phase II status. And from that point who knows how long it would take for the Xiaflex to actually result in noticeable changes? A few months? A year? 2 years? (rhetorical question)
I think Xiaflex in the pipeline will make doctors much less likely to do surgery, but will prove to be a terribly long wait for those currently suffering from Peyronie's.
Off Label is a term used to describe the use of an APPROVED drug for something that it was not approved to treat. Only drugs already approved to treat some existing condition can be prescribed for off label use. Xiaflex on the other hand is a drug still in development which has not yet been approved for any use by the FDA. Therefore it can not be prescribed at all without some unusual dispensation from the FDA. That is the reality. Its simply not here yet. Its on the way, but not here yet. - George
Yeah, of course. Sorry for the confusion. But I meant because Xiaflex is in Phase III trials for Dupuytren's, and only Phase II for Peyronie's, it will likely be available to Dupuytren's patients much sooner, maybe by 2009. But unfortunately for us, that doesn't mean that it will be available for Peyronie's then through off-label prescription b/c until further research, we won't know if it's as safe to inject into your penis as into your hand. Although, if any uro is willing to take the risk and offer it off-label to patients, I would imagine it could be a lucrative move.
And if I may vent (just a tiny bit), does anybody else find it interesting that Xiaflex (assuming it works) is being developed by a smaller, start-up pharmaceutical company??? Imagine if Pfizer or Bayer would/had put their resources into this! But I guess it's not profitable enough for them, and in fact, it could have a net decrease on profits from selling expensive erection pills. To me it goes to prove what Winston Churchill once said about capitalism (ok, actually he said it about democracy): that it was the worst system except for all of the others.
jxyz:
Why did you not just post the link to this research instead of writing the whole dissertation? I don't think that many guys will take the time to read it here. I know that I will not be reading it in detail.
Just my 2 cents worth!!!
Old Man
jxyz, I suspect there are a lot of agents out there that do things that *might* be helpful for Peyronies. The problem is, what are the short and long term side effects of these agents? These are issues that would take a lot of time and money to sort out. And if no one is willing to put up the millions of dollars necessary to sort out those issues to the satisfaction of the appropriate regulatory agencies, those agents will not be put into use. Its that simple. When you look at the research, there are all kinds of possibilities, but few of them are really viable in terms of attracting the necessary investment to bring them online. Personally, I am quite daring. I have been using a lot of supplements that have been helpful to me. But even if not thoroughly tested, these substances have all been in general use for some time and are pretty much vetted out in terms of major risks. I would not dare to touch some of the more exotic stuff even if I could get a hold of it. It would be risking my life. No thank you. Not when I can block many of these same pathways with something like Pentoxifylline which has a long history of safe use. - George
Fascinating new directions (though I agree very hard to read these online I only post entire articles if the links do not really go to full text). Lots of new stuff to hope for.
Tim
Today I mailed six articles pertaining to Pirfenidone to Dr. Levine and Dr. Fedunok, a uro at University of Chicago.
We have to make ourseves and our pain heard!!! You people do great research here yet you sit on your ass with the potential solutions.
We have to be vocal!!!
In order to make their suffering heard a group like Mothers against Drunk Drivers are very vocal. They are in your face vocal. Call your uro, print and mail your peyronie's articles, TGFb-1 articles, any promissing research. Keeping it to ourseves on this board is not going to help us. Be vocal!!
I'll bet you that within a month I well be taking Pirfenidone prescribed by Dr. Levine. I will not take no for a answer! I will not sit by quietly while I suffer!
I implore you to call and write your ero. Like I said, Mothers against Drunk Drivers had to harrass lawmakers to get their point heard. I am saying harass, persistently, unrelentingly!
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jxyz:
Sorry that you take such an approach to the good work that has been done so far on this forum. I don't think that you have made many points with the members by posting is such bold type and using exclamation marks to end your sentences.
I believe that most of us on this forum are grown up adults and we do not have to resort to such tactics to make ourselves heard or known.
Hope you have good luck with your emailed articles and your visit with the good doctors you mentioned.
Old Man
Quote"Sorry that you take such an approach to the good work that has been done so far on this forum."
It's not good work if it doesn't get off this form and infront of our eros, senators, congressmen. How many congressional forums on breast cancer have we seen on CNN, plenty! Women had to become activists to get better healthcare. Many of them unashamedly living by the words (History is rarely made by the well behaved woman) The same women beleaguered, bothered, badgered all those who can make positive changes for better female healthcare. That is what men need to do and that is how we will draw more attention and funding to our disorder, by becoming activists.[/size]
Quote"I don't think that you have made many points with the members by posting is such bold type and using exclamation marks to end your sentences."
Deal with it!
Quote"I believe that most of us on this forum are grown up adults and we do not have to resort to such tactics to make ourselves heard or known."
What is your tactic old man? Sit on a (single) forum, remaining unheard and unknown. Let me quote Newguy;
Quote"I've spoken with very educated professionals in the medical field who are unaware of peyronie's. It's quite shocking really."
I am saying become an activist. Write the endowments who supply money for research grants...write to at least two eros a day. Beleaguer them, bother them, badger them. Don't let them forget we are here.
To bad you choose to live a quiet life of desperation. I'm not going to end up like you old man.
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jxyz:
No, I don't have to deal with it, you do. I have been on this forum as long as any one and have a good reputation of helping others. So, if you think that you can come so strong, why don't you just go to another forum where your kind of remarks would be accepted and appreciated.
We do not have to put up with the likes of your sarcastic remarks at any time. If you would use the forum in the manner that it is set to be, you would be better served. Just keep up what you are doing and see what happens.
Thanks for your ridiculous remarks posted in bold type. Are you so small that you have to use large letters to get your point across?
Old Man
Quote from: jxyz on July 05, 2008, 07:00:43 PMTo bad you choose to live a quiet life of desperation. I'm not going to end up like you old man.
With an attitude like that you are not going to get much respect from many of us around here. If you think we are all doofisses, you are welcome to try to show us all how its done, but don't try to use our forum to ridicule us. And you are going to find out that there is a lot more standing between you and Perfinidone than Dr. Levine. You have better be writing letters to the pharmaceutical company that makes it AND to the FDA among others. As much as I would relish a prescription for Perfinidone (and make no mistake about it, I most certainly would love to have access to it), there are some good reasons why I can't get it at this point. Turning it loose to all those who might benefit at this point could end up jeopardizing the long term viability of the product. Testing and marketing these products costs gazzillions and all it takes is one misstep and the whole project is back to the drawing board. You are so wet behind the ears and so arrogant, you have no right to respond to Old Man the way you did. He has probably done more to better our lot than you will ever achieve. Those are my sentiments. - George
Dear jxyz:
Most of us can understand and empathize with passion. Most of us feel strongly about various aspects of this problem. But we are not all things for all people. We are not necessarily "advocates", or activists in a cause. We are here because we share a problem and this is a support forum. So while I understand your passionate feelings about the need for advocacy, that does not make it proper or your right to engage in personal, ad hominem attacks on individuals.
I could point out how much help Old Man has been to others, but others already have done so. His help has been primarily through discussing and advocating - here - what has worked for him. What he has recommended has helped innumerable people.
A life of "quiet desperation"? I don't think so. He has had Peyronie's for over 50 years and has found a way (unlike most of us) to control it and to regain his penis' function. He has an active sex life in his seventies. Sounds more like a goal to aspire to, rather than a path to revile. The fact that folks will surely rally to his defense will speak to the value of what he shares.
I do not need to know why you suddenly shifted gears here. You have made over 20 posts, most sharing up-to-date information on research with appended questions regarding the applicability to Peyronie's care. You have expressed gratitude to others for the information that you have received that helped (i.e. your post expressing thanks for the information on supplements). https://www.peyroniesforum.net/index.php/topic,22.msg12909.html#msg12909
More recently, you have expressed frustration, describing the supplements as those you have "wasted" your money on.
We can all relate to frustration, but "shouting" at others through the use of larger fonts, along with personal attacks will not be tolerated. We do not have a ton of rules here, but have thrived through decency and mutual support. Please respect this accepted and commonly agreed upon mode of interaction with others here.
Tim
I'm also going to point out the dubious effectiveness of such an "advocacy" -- there are promising treatments on the horizon for MS, arthritis, alzheimers, etc. -- diseases that affect a much, much larger portion of the population. If all it took was advocacy these diseases would be a thing of the past - there are charities and infrastructure devoted to these potentially fatal and more debilitating diseases than there ever will be for a disease that affects a small percentage of a gender that makes up less than half of the population. I hate hate hate the FDA and the red tape it needlessly winds around progress (and the fact that enough $ can get something like Vioxx through) but it's in place to help ensure that the incredibly complex drugs that are being manufactured won't do more harm than good.
I check this forum more than all of the others. Why? Because I'm young and I hate that I have this disease, and this forum is the greatest hope we have. Sometimes I despair too, and think the economy will collapse or some other disaster will occur and stall or stop this research, but you're wrong to take out that fear/anger/aggression on the small population of people out there who are WILLING to help you. Most Uro's don't know much about Peyronies Disease -- most people on this forum do. Please, go and advocate for us - but don't cut off your nose to spite your face.
To Old Man, Tim, Ocelot, George:
Well said!
Peyronies is a form of fibrosis, and there's lots of research already going on regarding fibrosis, for other reasons. Fibrosis is a big problem with radiation treatment for cancer, for example. New antifibrotic drugs may very well turn out to be effective against Peyronie's as well as other, higher-profile conditions.
Also, let's not forget: the one and only drug which has definitely shown success against Peyronie's - injectable collagenase - is in Phase III trials and apparently still grinding its way toward the market. These things take so ungodly long - the road is so twisted - that eventually the "process" just becomes part of the landscape and we stop thinking or talking about it, because it's frustrating. But in this case, I think it will go to completion, and guys who actually have Peyronie's (and not some conjunction of other problems and anxieties) wil be able to get real improvement.
If you want to be an advocate, then buy shares of Auxilium, show up at a stockholder meeting, get in front of the microphone and demand to know what's happening with this product.
j, Thanks for a few words of sanity here. As you note there are products in the pipeline with huge potential and Collagenase is one of them. AND there are a number of doctors AND researchers that ARE sympathetic to our plight. We need to encourage them, not anger them by insinuating that they don't care about us. Thanks again for a great post! - George
???
I ran into this document titled "
Medical Management And Surgical Management Of Peyronie's Disease" today...
http://www.medicalnewstoday.com/articles/117599.php (http://www.medicalnewstoday.com/articles/117599.php)
with the following statement about medical management (vitamin E, potaba, Colchicine, Tamoxifen, Carnitine, Pentoxifylline, and PDE5 inhibitors ):
QuoteIt is clear that rigorous well-designed controlled studies have in the past not been uniformly done. They are needed, and we are in an era where that deficiency is being addressed.
I'd like to know just
where these studies are being addressed? Anyone know of anything?
Check the article. Xiaflex could launch by late 2009. We all could make good money pn the shares based on what we know. However, i will be very happy if there is a cure for this next year.
http://www.marketwatch.com/news/story/swinging-fences/story.aspx?guid=%7B4D97A2D5%2D0A50%2D47A8%2D9A74%2DD04406AB3C93%7D
BioSpecifics Technologies Corp. Reports Second Quarter 2008 Financial Results (http://www.marketwatch.com/news/story/biospecifics-technologies-corp-reports-second/story.aspx?guid=%7B960A6392-A726-4E37-8ABC-34B2A9F81347%7D&dist=hppr)
Quote from: Wall Street Journal Digital Network"In the second quarter, successful pivotal Phase 3 results for XIAFLEX(TM) to treat Dupuytren's Contracture were announced by our partner Auxilium, Inc. We continue to expect a biologics license application (BLA) filing for this product with the U.S. Food and Drug Administration in early 2009. In addition, we expect Auxilium to initiate a Phase 2b trial for XIAFLEX in Peyronie's Disease later this quarter," commented Thomas Wegman, President of BioSpecifics Technologies Corp.
This does indeed sound promising! I suspect the trick here will be to keep the lid on inflammation with current treatments whilst blowing away the scar tissue with Xiaflex. Once the scar tissue is gone and the whole thing has healed, there should be no further stimulus for any further inflammation. - George
I found this post over on the BTC Discussion forums:
"I have been in the Xiaflex test program for near 3 years. I would drive to Erie, Pa 70+ miles countless times over that span. First the drug was tainted with moisture and I had to wait a year for another chance. Then I recieved the placebo and had to wait again. Then I finally got the real thing and my first joint on my little finger went from 50% bent over to 0%, straight over night. I need only one more injection for the next joing up and my hand will be completely recovered. I am enjoying doing small things I took for granted for years like shaking hands, and for all of you whom are waiting for this drug it is purely amazing, do not get surgery, I waited and it is worth it. NO SCARS, and use of your hand within days."
Granted, this was testing done for Dupuytren's disease but CLEARLY this is promising news!!!!
Thoughts?
I am starting with my uro, Culley Carson at UNC Hospital on Monday, and maybe this is a trial that I can be put on... I have heard there is a trial of Xiaflex with Peyronie's taking place in Virginia.
I posted this on another thread, but check this out http://www.theindychannel.com/health/16902359/detail.html
Also, this is just an average Jane on youtube http://www.youtube.com/user/samanthahoffman
I think I just watched her last video, and even though it didn't look that great (def not 100%) she said that it made a huge difference, so that's good!
I have much hope that Xiaflex will come to cure this terrible condition. No one should have to suffer such a ridiculous disease.
this looks so promising. wow i am crossing my fingers for such a thing. This would not be a cure but definitley help a lot of us I bet. What is the deal and where are they currently for using this for peyroines?
I found this site after reading an article in the alternative magazine Nexus. I jotted down the Website and accessed it when I got home.
The info on stem cells is similar to the contents of the Nexus article, which leads me to believe that the company that produced the product paid for the article. Nevertheless, can any of the knowledable members of the forum tell me if it's possible to produce stem cells by ingesting or topically applying colloidal silver? Wouldn't that be wonderful.
Of course I'm talking about a quality brand, which this manufacturer says its product is ::)
\http://www.live-silver.com/StemCells3.htm
They're in the second part of the second stage of testing for Peyronie's, I think I read that they expect to inject their first penis with the substance early next year. I hear the manipulation after the Dupuytren's shots don't feel to good, so I'd expect the Peyronie's ones wouldn't be too pleasant either. But there's something about this condition that I doubt very many of us are worried about the pain.
I understand that dosing with Xiaflex will begin late this month or early next month. Does anyone have additional information?
Second question - For anyone with some knowledge of anatomy. It seems that Xiaflex injections are safe for Dupuytren's contracture. Can we then assume it will be safe for penile injections?
I don't know, but I see that all these money magazines are now recommending it, and the prices has gone up a lot this summer. Damn it, I've been thinking I need to set up an account to invest in it, but have just been too lazy. Really need to get on that and do that. You make money in the stock market when you have information that others are not aware of, and we all have definitely been aware of this stuff long before most market people probably were. Now the google news hits for Auxillium is relatively huge to what it has been.
ohbj1
Penile Injections. Don't Do It. I have corporal fibrosis from trying Trimix and it made things worse.
I know I have tried all things legal and some that are not. Just be careful what you inject into your penis.
IMHO.
Jackp
For injections in the hand, I doubt that they do any numbing first. Which could explain why there might be some pain afterwards. I know for Verapamil injections from personal experience that they do numb the penis first before the injections. So I would think the same would be true for Xiaflex.
As JackP points out, there are some risks. But there is also some documented evidence that the Verapamil injections do help in some cases. I suspect the same will be true for the Xiaflex. Has has been stated many times on this forum: What will work for some won't for others and vice versa.
I have Dupuytren's (along with Peyronies Disease) and I've been following the Xiaflex story for over 10 years now. I haven't had the injections, but I've read first-hand reports and I think I understand the issues.
With Dupuytren's you have hard, tough cords restricting the motion of your fingers. The cords are usually pretty distinct from the surrounding tissue, and just severing the cord is often enough to restore fairly normal motion. Xiaflex is injected into one spot in the cord and allowed to dissolve the collagen for a while; then the finger is forcibly straightened with considerable force to complete the job by snapping the weakened cord. There is literally a 'pop' when that happens. To prevent the enzyme (collagenase) from damaging surrounding tissue, they don't inject more than is necessary to simply weaken the cord enough for it to be snapped.
The procedure has worked well in trials. But obviously Peyronies Disease is quite different; the collagen is more integrated into the surrounding tissue, and that tissue is very easy to damage, and very hard to repair.
So I don't know how they'll use Xiaflex for Peyronie's. Maybe they'll inject small amounts in several spots and hope to weaken the collagen enough to restore some stretchability. I don't think it will be a 'cure', because it won't be possible to dissolve all the unwanted collagen. But with a careful strategy of multiple and/or repeated injections, I think it could really improve things for a lot of us. The key will be urologists who care enough to experiment, do the imaging and the followups, and try to refine their technique.
I think it will work.
Thanks J,
That was a very good observation and yet another reason why I have not returned the letter I received from a medical group that is planning to test Xiaflex on Peyronies. I'm bad, but not as bad as a lot of the guys on the forum, so I don't want to end up damaging myself further and needing surgery.
Bodoo
Quote from: j on July 07, 2008, 03:24:52 PM
Peyronies is a form of fibrosis, and there's lots of research already going on regarding fibrosis, for other reasons. Fibrosis is a big problem with radiation treatment for cancer, for example. New antifibrotic drugs may very well turn out to be effective against Peyronie's as well as other, higher-profile conditions.
Also, let's not forget: the one and only drug which has definitely shown success against Peyronie's - injectable collagenase - is in Phase III trials and apparently still grinding its way toward the market. These things take so ungodly long - the road is so twisted - that eventually the "process" just becomes part of the landscape and we stop thinking or talking about it, because it's frustrating. But in this case, I think it will go to completion, and guys who actually have Peyronie's (and not some conjunction of other problems and anxieties) wil be able to get real improvement.
If you want to be an advocate, then buy shares of Auxilium, show up at a stockholder meeting, get in front of the microphone and demand to know what's happening with this product.
I spoke with Dr. Gelbard (Burbank, CA) re Clostridium collagenase, and he said it's now in Phase III trials for use in Dupuytren's contracture patients only (not Peyronie's). He said that it's looking very good, with little or no adverse reactions. He is now conducting Phase I trails of collagenase treatment of Peyronie's patients, and he needs more participants.
I do think that translating Xiaflex's success with Dupuytren's into success in treating Peyronies is going to be difficult. That is why I suspect that in the long term Alagebrium Chloride will likely turn out to be the more successful solution. Instead of targeting Collagen like Xiaflex, Alagebrium targets the crosslinking itself which defines scar tissue. - George
I believe Xiaflex is beyond Phase I testing and the current trials will be considered Phase IIb. Does anyone know how many men have been previously tested with Xiaflex for Peyronies? I believe, but am not sure, the original company may have done some testing.
I went to the Auxilium web site and they indicated that Xiaflex resulted in an average 25% reduction in curvature. Since I have a severe case, a 25% reduction won't do it for me. Has anyone seen the complete results from earlier testing to see if those with more severe cases have had more success in terms of percentage reduction?
Thanks.
I think the goals of early stage testing are to show that a product does no harm, and has some positive effect. So, dosage and treatment plans will be very conservative. The last thing they want to do is inject too much, cause collateral damage and blow the whole deal. 25% improvement is enough to convince investors that this product will sell. I have no inside knowledge, but based on how this drug works it seems to me that more aggressive treatment is certainly possible and will be tried in time.
Ohjb1,,,,I haven't had any experience with this Xiaflex,,,,but i did have great success with vita-E and Topical Verapamil and i had a severe case of peyronies,, check out this website as it kinda comes close to what i looked like, www.revistaciencias.com/publicaciones/EEElkyEkFkxaTlhnDF.php
I was on the Topical and E and seen results after 3 months and much better results after 5 months..was very expensive but i felt it was worth it to get my penis back straight....MY penis looked much worse than this picture,,twisted and bent like a donut all the way back into my groin..
This is just my opinion and results for me,,,,,,,,kimo
is topical verapamil something you have to get a doc's prescription for?
have subsequent tests after the one on the following site have had mixed results about topical verapmil??
http://www.phoenix5.org/sexaids/basics/penile/VerapamilPR042600.html
The site itself claims the patent holder/inventor was ridiculed by those who had seen sporadic results from verapamil injections....so I assume, scientifically, this is still in a grey area?
Wayne, Topical Verapamil or "TV" as it is known in many circles does indeed require a prescription. It was the subject of intense conversation on this very site some months back when it was just emerging. It was widely panned by guys who tried it and then claimed it to be ineffective and also implied that its distributor was lacking in ethics and not telling the whole truth about it. But now you have people like Kimo claiming that they were helped by it. At this point, I think, perhaps, it is like a lot of Peyronies treatments. They seem to work for some people and not for others. There is still a lot about Peyronies that is really not well understood and I believe that various efforts to control it may conflict to prevent improvement or conversely be synergistic to facilitate improvement. Those few who are benefiting or have benefited from TV may actually have chanced upon such a pathway to improvement. So if I were to look to TV for help, I would seriously study the efforts of those who have gained benefit from it. - George
George,,,,you are correct in saying the TV doesn't help everyone...When my URO prescribed it for me, he said it might not work,,,BUt he did also say it only works for a few men and it was worth the try..I do admit that i was very fortunate that it worked for me...
I forgot to mention that in my post..I felt that it was worth the try and was willing to take a chance,,and i am so glad i did...i was very punctual about putting it on every morning and every evening, was willing to do anything at that point to get my penis straightened out...My URO also said that he felt vita-E would help the TV to do a good job,,,IT Worked..
This is just my opinion and experience,,,,,,kimo
Nick, I'm not sure that this is the best venue to look for a donor. ::) - George
That's what I'm thinking. If John Wayne Bobbit can have it cut off and then star in porn a few years later, shouldn't our conditions be simple? Oh well, that rant isn't productive.
Mr. Bobbit suffered major trauma and yet did not end up with Peyronies from his ordeal. With that degree of trauma one would expect total loss of function due to a massive case of Peyronies. But what this is actually demonstrating is that trauma is JUST A TRIGGER. It is NOT the cause of Peyronies. Thats why we have to address the ROOT CAUSES. Those are the forces that establish and fuel Peyronies disease. And those are the forces that it is important to identify and remediate. - George
From what I have researched, you hit the nail right on the head George. It seems like certain people for whatever reason are more susceptible to develop Peyronie's as a result of major or minor trauma to the penis. Not every single person who injures their penis in some way develops Peyronie's. Because of how much variability is involved with not only the onset of this disease but the progression as well, I doubt there will come about a method that will cure or even definitely help each and every person's Peyronie's. From reading everybody's stories on here, it seems every person is different in regards to how treatment has affected them. I am new to this whole ordeal and from those who have read my posts you can tell that I find it very hard to stay positive. I am being proactive though and am trying everything that I possibly can to help myself to have a better lifestyle. I may never be completely back to my old self but I just refuse to believe that I will never be able to have sex with my girlfriend. We both love each other very much and our relationship was progressing to this point when my symptoms happened. It has hit me very hard. She has been nothing but helpful in every way and went with me to my appointment with Dr. Carson at UNC Hospital though he did not suggest that we bring her in when I mentioned that she had come with me. He wanted to wait until next time when they do the doppler scan as he could not feel any scar or plaque during my visit. When I have erections though, it is most certainly there... :(
These are just some thoughts. Perhaps the Xiaflex testing will continue and one day that by itself or perhaps that in conjunction with another form of as yet undiscovered tretment will end up curing this...
I know for a fact that testing with Xiaflex is about to begin. Has anyone receive any written notification from their physician's with the details?
Shouldn't this information appear on the clinicaltrials.gov website?
alcohen, Actually, the more I have learned about Peyronies, the more optimistic I have become, both about myself AND about others. For one thing, I have learned that the process underlying Peyronies is referred to as "Glycation". And as I have learned more about that process, I have become very impressed as to the number of things I can do to limit that process AND the amazing progress of research aimed at stopping and even reversing that process. I really do think that the future, even the near future, holds great things for all of us. We are all so blessed to live in the age that we do. Only a few short years ago there would have been no Pentox, no VED, and no forum like this one where we can all learn and share our experiences. Also remember that what appears to be Collagen can actually be simply inflamed and swollen tissue that can immediately return to normal if the inflammation is quelled. ONLY an ultrasound can tell the difference between inflamed tissue and actual scarring. And I believe (someone correct me if I am wrong) that a Doppler Ultrasound is used to analyze blood flow. In any case I wish you the best in this. But I do think the future looks bright for all of us. We just need to do what we can to take charge of our health and make it better and know that as we do more and more tools will be coming available to us as research and development move forward. - George
ohjb1, I found this information at:
http://www.curepeyronies.net/index04Xiaflex.html
I am not sure how recent this information is, or even how accurate this website is. But it seems interesting and food for thought...
"Auxilium Pharmaceuticals has the rights to a potential new treatment for
Peyronies. They have named this new product Xiaflex and the hope is that it
will reduce the scarring associated with Peyronies. I have been able to get
some additional information about the upcoming testing that I believe is
reliable, but not guaranteed.
There have been a number of delays in the clinical trial's schedule. Testing
was to begin late in 2007, then in the first quarter of 2008 and now it is
anticipated that it will begin the summer of 2008. The testing procedure is
moving forward and the company has sent the proposed clinical trial protocol
to the investigators who will run the drug trial. There will be multiple sites; at
least 5 different testing centers.
There will be at least 2 screen out criteria. 1) Calcification of the scar tissue
area and 2) Failure to achieve an erection via injection. This criterion makes
sense because calcification or hardening of the area will make it more difficult
for Xiaflex to soften the plaque. Failure to produce an erection indicates
Peyronies and a serious additional erectile dysfunction component. Let's be
realistic. The purpose of dissolving the plaque and straightening the penis is
so we can engage in sexual intercourse.
Stay tuned. Although there have delays, it is moving forward towards a clinical
trial."
The information posted below by alcohen just makes sense. Auxillium has a purpose of getting Xiaflex on track for approval for use on Peyronies. They will not achieve this by enrolling the most difficult cases in their trial. But that DOES NOT MEAN that Xiaflex will turn out to be ineffective against either calcification OR ED. It, in fact, may or may not prove helpful. It DOES mean that it would certainly be more difficult to achieve effectiveness in such cases and so that is definitely not where they are going to start. But IF approval is granted for Peyronies in general, it WILL be used in such cases as well by doctors who are willing to test the limits. Auxillium is just not willing to risk the extra time and money testing such cases might cost them at this point. So, while I think this is good information, one has to be very careful what one reads into it. To any out there with calcification OR corporal or smooth muscle fibrosis OR even a leakage type scenario, I would say not to give up hope. The natural course of the body is to heal and there is ALWAYS hope for that to happen. - George
sgtnick:
I may be wrong and stand to be corrected, but believe it pronounced as follows: zee-oh-flex.
Most words starting with the letter X it takes on the sound of Z, so that is my thinking on it. Others may know better from other sources, etc.
Old Man
Interesting news out this morning: Biospecifics is quietly upping the ante on Xiaflex for treatment of Peyronies by buying rights to its use ahead of time rather than paying royalties later on. This essentially means that Biospecifics, having reviewed the results of testing so far, have decided that they want to increase their risk on its success significantly by putting money down ahead of time. This reflects increased optimism on the part of Biospecifics as to the eventual success of Xiaflex in the treatment of Peyronies. - George
Biospace: BioSpecifics Technologies Corporation (BSTC) Buys Down Royalties for Peyronie's Disease 9/5/2008 (http://www.biospace.com/news_story.aspx?StoryID=108788&full=1)
George, i do hope that you are right. However, i suspect that the optimism is due the results on Dupuytren's Contracture. I do not know of any results for relatively large trials for Peyronies.
GEORGE999,
In your opinion when do you think there will be a cure or something we can take for this??
Nemo, To be really honest about this, the term "a cure" makes me really uncomfortable. I see a lot of very effective treatments, but no real silver bullet, at this point. I think guys who really work every angle, even now, can pretty much achieve a cure. I have held this thing at bay for a long period with ALC (along with really working on the healthy lifestyle aspect). And now, with the addition of Pentoxifylline, it is REALLY getting pushed back. I really believe that the roots are Peyronies for most guys are in a basically unhealthy lifestyle. And I think that in most cases they are completely unaware of what constitutes an unhealthy lifestyle. And without serious lifestyle changes, no amount of treatment is going to solve the problem. BUT, I am convinced that it will be easier to CONTROL Peyronies as new products such as Xiaflex and Alagebrium come on line. And for those who are resistant to lifestyle changes or have health conditions (such as prostate issues or genetic issues) that complicate the whole thing, the VED is the best option. In fact, I consider the VED to be the closest thing to a silver bullet available today. But of course, it is not a silver bullet in the sense of a cure, but it comes very close in the sense of a treatment. I think there are quite a few guys who are nearly totally asymptomatic as a result of regular and disciplined VED usage. - George
George999 - you seem to be extremely knowledgeable. I have an 80 degree upward that essentially renders me nonfunctional. I have tried verapamil with poor results. Dr. Levine has recently suggested a traction device, which in his opinion would help my condition. Do you prefer the VED vs the traction? If you prefer the traction would you suggest a particular brand or direct me to their website.
At this point, I do not want to take any additional medication because I am only a few months post a cardiac bypass operation.
ohjb1,
Dr. Levine is affiliated with a company called Fastsize. You can google and get their web address. LEvine will also provide you with a discount code for $30 off. I'm using one now post surgery to stretch the graft and to regain some length lost during surgery.
Quote from: lwillisjr on September 07, 2008, 09:41:12 PM
ohjb1,
Dr. Levine is affiliated with a company called Fastsize. You can google and get their web address. LEvine will also provide you with a discount code for $30 off. I'm using one now post surgery to stretch the graft and to regain some length lost during surgery.
lwillis, do you mind sharing how much length you lost? The grafting procedure is supposed to result in lower length loss relative to the nesbitt from what i understand, so it would be good to hear your experience with this.
ohjb1, I definitely would choose VED over traction simply because the VED is, in my thinking anyway, a much more proven approach than traction. If you page back through the VED thread in this forum, you will find multiple success stories resulting from VED use. Traction is a new approach that I simply don't have as much confidence in. And that is not only due to the fact it is new and unproven, to be honest, I don't have as much confidence in the concept. All of this of course does not mean that traction doesn't work, but I suspect that it never will be as good of a solution as the venerable VED is. But you have to remember, this is not only about treatment options, this is also about business and about doctors who may have money invested in a particular product or concept. This is a sort of seamy underside of medicine. So, beware. (Just my opinion) - George
Thanks George, I appreciate your feedback
Wayne999,
No problem. Reminds that I need to update my personal information as well. Dr. Levine had me originally wear the Fastsize device during my initial treatment of the VI injections. Neither worked for me but I did pick up 1 centimeter prior to the surgery. I was right in the middle of what I understand is a normal distribution of just under 6" when erect prior to the addition of the 1 centimeter. As a result of the surgery, I have lost about 3 centimeters.
I am again wearing the Fastsize device per Dr. Levine's recommendations and he believes the length will come back as the graft continues to heal and stretch. I will tell you, and I never though I would say this, but I gladly give up the 3 centimeters to become straight. The wife says she does not notice a difference. If she is saying this to make me feel good.......... it is working ;D
GEORGE999 - when will Xiaflex and the other new treatments ( algaebrium??)) come on board for public useage??????
How come these 2 products Xiaflex and Alagebrium will take so long 2 years or more - is there nothing sooner??
Xiaflex is in trials now for Peyronies, so it should be available in a few years if all goes well. Alagebrium is in trials now for ISH, once it gets approved for that, research physicians may begin trying it off label for Peyronies. So alagebrium is a few years out. - George
Iceman,
The short answer is that they have to have adequate studies to find out if it works or makes things worse. I miracle cure forum today would take at least a few years to get to market if it was a new drug.
This condition was documented 250 years ago and we still have no consistent treatment. Sadly many diseases have no good treatments and many of those treatments kill people. By those standards, 2 years is right around the corner.
Just to briefly note that Synvista, the maker of alagebrium has just announced success with a somewhat breakthrough product for heart disease. This should bring them additional revenue to help fund alagebrium research. It also demonstrates Synvista's expertise in this area. - George
Data Confirm Synvista Therapeutics Haptoglobin Diagnostic Test Kit Success In Rapidly Determining Cardiovascular Risk In Patients With Diabetes (http://www.medicalnewstoday.com/articles/121190.php)
Has anyone on this board been contacted about the Xiaflex trials? I have
Auxilium has announced that Xiaflex Phase IIb (dosage) trials have begun. There are 120 patients at 11 sites. Criteria: Ability to maintain an erection and curvature of between 30 degrees and 90 degrees. Good luck to all the participants.
How does one volunteer or participate in the study for the phase IIb trials?????
Interesting that this site has been operating for several years and today we have the first piece of significant info and there is not more interest
Your post is #493 on this thread, and most of the others deal with Xiaflex!
how does one get involved in the trials if out of the USA
Based on my limited knowledge if you are outside the US you may want to check Google and insert clinical trials.gov and then type in basic search, type in peyronies and see what the criteria is concerning anything going on outside the US. right now information is not posted on this site. just keep checking. It is discouraging that the trials will have so few people.
I spoke to the nurse in another doctor's office (not Levine) and she said they will initially be dosing 10 men, but having a waiting list of over 100.
has anyone heard of pirfenidone?? - is this approved and does it work??
Iceman, Pirfenidone is really pretty much a "better" Pentox. It does the same thing Pentox does, only more effectively. It is targeted at the same types of diseases Pentox is. The difference between the two is that Pentox is an old tried and true generic drug and Pirfenidone is a brand new product still undergoing trials whose long term safety risks have not yet been assessed. It has not been approved for general use and is, I believe, currently in Phase III FDA trials. It IS being provided for people who are literally DYING. It is not available for people with Peyronie's and probably won't be for a long time largely due to potential safety issues and lack of specific FDA approval for Peyronie's. Eight to ten years from now it *may* be used to treat Peyronie's if all goes well. Oh ... and if it were available now, I guarantee, it would cost you far more than you could afford in a life time. So, while it is certainly of interest and has actually been discussed here before, it is not really of any current usefulness in terms of Peyronies. For people who are dying of fibrotic diseases, though, it may well save some lives. It is that good. - George
GEORGE999 - if its that good maybe there are places in India/China that rip off the ingredients that we could buy it??
I really want to put a drug from unethical rip-off artists from China in my body as a way of improving my health. These are the people that don't blink at contaminating our pet food or our children's toys.
How about putting Melamine in milk to increase it's apparent protein content despite the fatalities associated with doing that?
At least corporate criminals get the death penalty in China - they got that going for them.
Tim
To Hawk and Tim's comments I would add this. Pirfenidone is an experimental drug whose long term effects are unknown at this point. Its short term effects are very impressive. But what about ten years from now? WE DON'T KNOW THE ANSWER TO THAT QUESTION YET. Do you really want to take that sort of risk to fix your broken penis? AND, we know its a great fibrosis drug, but we don't even know at this point how effective it would be on Peyronie's. While it quite possibly be more effective than Pentox, it very likely won't be a magical cure. I'm sorry, but I most certainly don't want to make that kind of gamble for my penis and I am VERY willing to take REASONABLE risks. And TO THIS add the risk of buying it from an disreputable source, I think you would be asking for major trouble and possibly death. This is a drug that I would take IF I WERE DYING. Since I am not dying, I think I will wait a few years and let some other people go first, then make sure I am buying the real thing. And I would strongly suggest that you do the same. - George
On Xiaflex: do you guys think it will be covered by the better insurance plans? I've heard that ED drugs are (at least partially) covered (not sure if that's true), but that usually birth control pills are not (raising issues of unfair gender treatment).
Anyways, I think the surgery is covered, so why not the less invasive Xiaflex?
I ponder this because I just graduated, and don't like my job, but it has great insurance benefits. If Xiaflex takes 2 years or less to be approved for Peyronie's, I'm thinking I'd be a fool not to wait it out.
Jack, My thinking on this is that unless you are really in deep trouble with Peyronie's, it will most likely pay off in the long run to simply use current non-destructive treatments (Pentox, VED, etc) to keep things under control as much as possible because, definitely, there are going to be more options in the next few years. And the younger you are, the more likely you are to see very effective treatments before your youth is over. - George
Yeah George, I completely agree. Of course I should try to do what I can now. It's not like we can bank on the idea that Xiaflex will even be approved or highly effective, although it is promising. Just got some pentox from a mexican pharmacy. here's to that.
FYI, I just got a call from Sue @ Auxillium. Human trials using xiaflex for Peyronie's are recruiting now.
http://clinicaltrials.gov/ct2/show/NCT00755222?term=peyronie%27s&rank=1
There's none near me, but dammit if you're close go sign up.
I too, just received a call from Auxillium advising that the recruitment for volunteers is
starting now. Apparently the study will run for 36 weeks with a 6 week interval between
injections. If you can afford to make 6 trips to one of the locations, I believe this is the
best course of action available. I'm attaching the website --
http://www.clinicaltrials.gov/ct2/show/NCT00755222?term=peyronie%27s&rank=1
Good luck -
swbasil
well damn, I might just have to fly out to LA 6 times if I can get on there.
And this is only Phase II. Glaciers move quickly by comparison.
j:
In other words, none of us should hold our breath waiting for results, huh?
Old Man
In 1996, a small trial was performed at SUNY showing that injectable collagenase could release Dupuytren's contracture. Inject it, let it work for a few minutes - snap the cord. Peyronie's "plaque" is the same tissue, right near the surface, easy to locate, inject and image. There is little doubt it would work and there are no real safety issues. It's just an enzyme that dissolves this particular sort of collagen.
I'm now 57, 12 years older than I was when I first read that report, and in addition to Peyronie's, I've lost a fair amount of functionality in my hands to Dupuytren's. Many millions of dollars have been raised and spent - and some people have already made tons of money - but injectable collagenase, now called Xiaflex, is still not available. Trials for Peyronie's have years to go even if nothing goes wrong. By the time I actually receive an injection of Xiaflex, the whole middle part of my life will be gone.
J- man thats depressing - hey at least your alive lets all be thankful about that!!!
Ive had Peyronies Disease now for nearly a year and I am learning to live with it - Im doing everything thats on here - even went to see lue...lets just all stick together on this and help each other out and if we do come across anything that helps improve matters then lets post it here...
One other thing - can we start a thread here for people who have had the clinical trials and note their feedback,,,
My life is ok. I'm still functional. What make me angry, looking back, is the absolute inability of the medical industry to simply give us this product. Years go by, then more years... there's no real "research" going on with Xiaflex, today, it was all completed by '96. It's just bureaucracy, and greed, followed by more bureaucracy, and greed.
J - well at least they have started trials - isnt that progression? I mean this is a positive step in an area that we have absolutely no control over.
I can easily make the trek to the Virginia location and am doing everything in my power to be a part of the trial. I meet all the criteria other than the official diagnosis which I will not recieve until December 29th when I have the blood doppler ultrasound done. I will keep you guys up to date WHEN my trials begin. I WILL be taking part in these trials.
to alcohen - i am a little puzzled, if you had an exam why wasn't the ultrasound done at the time of the initial exam?
I was very puzzled by that as well! Many of you report that your uro has done an ultrasound at the same time as the first consult. The doctor, Culley Carson, is very knowledgable about Peyronie's disease accoding to numerous sources. He knew that was what I was going to see him about. After he did a quick hand-test on my penis I was very startled to see him start talking about getting me back in there for a doppler ultrasound... It takes me a little under 3 hours to get to his location so I was a little depressed at having to wait. I got more upset when I went to checkout and the receptionist told me that they only do this 4 times a year (this is at UNC Hospital Urologic Surgery department) and that I wouldn't be able to be seen until possibly November... This was on August 18th. It is not done by Dr. Carson, but instead someone in the "Vascular Studies" section of the hospital according to the form they sent me. I recieved two upcoming appointment cards in the mail yesterday. They are both for December 29th, with the first being at 9 AM to do the ultrasound and then a 10 AM appointment in the "Urologic Surgery" section of the hospital with Dr. Culley Carson. It is very frustrating to have to wait this long to have something done that should have been done long ago on me.
My first urologist told me when I asked that there was no scan that could be done to see if there was anything inside my penis... The second one told me that there was a scan that could be done but that there was no reason to have it done because nothing would be found by doing it and that it would be a waste of everybody's time. He is also the one that guaranteed I would be better in 3 weeks two months ago.
It is extremely frustrating because the Xiaflex website says that you need to have been diagnosed for at least 6 months to take part in the trials...
Sorry al, something doesn't sound right. As someone who has very good health insurance, i have seen 2 physicians who are considered Peyronies experts. both conducted the ultrasound at the first visit. Secondly, it seems as if you could move things up if you called another doctor who will perform the ultra sound at the initial visit. I don't mean to sound negative, but i don't think you chances of participating this current trial are very good.
http://www.menshealthpd.com/cm-pdz/index.html
Here is one of the website's detailing this urologist. He did a live chat recently and answers several questions here via video. I don't understand why it was not done upon my first visit. I think in the back of my mind that he did not expect to have to do an ultrasound after seeing my age and notes from my first uro who I forced to transfer to him ("NO PEYRONIES") and probably something on there about my ailment being in my head as he told me repeatedly... Obviously now he thinks otherwise. I will try to e-mail Dr. Carson tomorrow as to the possibility of either moving my ultrasound up or having someone else at a different practice administer it.
This is a crosspost, kinda, as my post got swept up in the healthcare off-topic deletion. I don't remember seeing anything about these two companies, and though they're just investigating anti-inflammatory and antifibrotic medicine for other maladies, we know that the jump (as in pentox or pirfenidone, etc.) can be made from drugs meant to treat more difficult diseases to ours.
So, has anyone heard anything about these companies? Or can they glean something I can't from reading them?
http://www.bio-medicine.org/medicine-news-1/New-findings-3A-The-anti-fibrotic-mechanism-of-plant-extract-Cpd-861-18031-1/
http://www.canfite.com/
I don't know much about either of them. Will try to look at em later.
Tim
I have found Chinese herbs in general to be pretty elusive. I have little doubt that they work, its just that it is nearly impossible to procure them and know that they are safe and contain only what they claim to contain or that they even do contain what they claim to contain. - George
Given the changes currently underway in China, I am even more suspicious. IT is easier for someone to market a "miracle herb" or pill, and mix in some black market Viagra, and charge an arm and a leg for it, than for them to actually go to the trouble of harvesting the real thing and preparing it properly.
Tim
But given that there's a statistic that supports that most new compounds come from plant extracts/combinations taken from the amazon (yes, there's a stat for everything I know) would it be so far off to suggest that there are Chinese medicines that might have helpful effects to the degree of aloe vera naturally? Maybe I'm being overly optimistic, here.
The East has a very different way of approaching medicine, however, so I imagine most herbal effects (assuming they aren't snake-oil) would be more on the preventative side than the curative -- preemptive/preventative care is a large part of eastern medical thinking,
The Amazon is in South America, but that fact notwithstanding, the problem with Chinese herbs marketed for the West is that they are not regulated.
That is a huge problem with an eager population looking for alternatives to the traditional allopathic approaches of the West. It is an undeniable fact that much of what we ingest from China has been doctored or had additives put into it, never mind the lack of environmental regulations regarding pesticides etc. If I were in a traditional Chinese herb store speaking to an old wise practitioner of Chinese herbal medicine I would feel a lot better than if I were ordering something from the internet or Whole foods or similar.
Tim
I am terribly anxious to hear from anyone who is currently receiving injections in the Xiaflex Peyronies Disease trial. 1/3 of those people will be receiving placebo treatment, so we should keep that in mind. However, I know I would be extremely encouraged by even one person with a dramatic result so please if you are lucky enough to be enrolled and receiving therapy right now tell us about it!
I would think that there would likely be prohibitions placed on those involved in the trials from writing about it before data has been compiled.
jackisback, that might be true for the doctors but not the patients. During the last Xiaflex trials for Dupuytren's Contracture, people described their results in detail on a DC forum that I follow. And those results were good. Peyronie's of course is different in some very significant ways, so there's no guarantee Xiaflex will be as effective, at least not without some experimentation and refinement of the treatment.
Unfortunately the cost of these FDA-mandated trials is so enormous that they're something of a "moon shot", i.e. the company gets one chance and if they can't show immediate success, they're likely to tank.
has anyone been on the xiaflex trials - LET US KNOW YOUR RESULTS PLEASE!!!!!!!!!!!!
maybe there should be a separate thread for this as this is a major thing!!
Quote from: Iceman on October 09, 2008, 01:13:54 AM
...maybe there should be a separate thread for this as this is a major thing!!
Iceman, This
is the separate thread for developmental treatments. Xiaflex and the trials are the primary thing discussed in this thread since developmental treatments are limited. If we took those out, this topic would be next to dead.
Hawk,Iceman,I have been selected to participate in the xiaflex test.I am go to New Haven,CT.on Oct 29th.I will give you all the info I can.
thx ticker....thats excellent - good luck...
Ticker,
That is great for you to be included in the trial! Please keep us informed regarding your experience and your progress.
roadblock
I'm am new to this site. I am in the xiaflex trials and have been injected. I am still somewhat bruised and sore. I don't want to get anyone's hopes up but I think it is helping. I will know more in the coming weeks. I don't think its the placebo. I don't want to get too specific with information that might in anyway jeopardise my continuation in the trials. I will try to check in as I can. This is my first post so I hope I am navigating and using this site as intended.
Quote from: Vernon21 on October 20, 2008, 11:48:41 PM
I'm am new to this site. I am in the xiaflex trials and have been injected. I am still somewhat bruised and sore. I don't want to get anyone's hopes up but I think it is helping.
Thanks for much for your contribution. Please do keep us informed.
VERNON21 - keep us posted - can you tell us how you feel and what improvement you have noticed and also how to get on the trials list.
Certain uros were selected by the drug manufacturer, Auxilim, to recommend patients of their for the trails. Those recommended go through an extensive screening process before being selected. There are only certain specific conditions they were looking for. The uros are what I think are the top ones in this field but I don't have a list. I do know in the practice I'm involved in I heard there were about 4 times as many men who wanted to participate as there were slots.
I believe my erection is now somewhat straighter and the weak point has improved. I never had a high degree of pain during erection. It will be easier to know more soon once the bruising has cleared up.
I hope this helps.
You know how they give cancer patients drugs even before they've completed trials and data collection and official approval just b/c it's considered unethical to refuse it to a dying patient? if only they felt such a necessity for people with problems with their most prized possession.
does anyone think that this will work:
http://au.youtube.com/watch?v=dN6eAr92mRo
he says that it works for 8 out of 10 people...
Iceman
Sounds like someone trying to get rich quick off Peyronies Disease. IMHO
Jackp
Iceman,
It's lame. He has a video for the same surgery that everyone else does. Some use SurgiSIS and others use other tissue for grafting, but the surgery is the same. There is nothing new or interesting here.
Also, since you posted this in another thread, and no-one had much to say, that should serve as a clue that it is not too scintillating. I also don't think that multiple postings of the same post help the forum, and it is in fact against forum policy (though moving a post to a new area is OK).
Tim
tim
I think you should have a short look on the video. It is not the vid about surgery that was posted in the other thread, but it's about stretching. I was wondering too if anyone here had experience with this. ???
didi
Quote from: didi20031 on October 27, 2008, 02:18:01 AM
tim
I think you should have a short look on the video. It is not the vid about surgery that was posted in the other thread, but it's about stretching. I was wondering too if anyone here had experience with this. ???
didi
I believe that various forms of stretching do hold promise, but when the guy started mentioning ordering his video and clicking on the "buy now" button, it didn't really speak well for his credibility.
I am going to be in the Xiaflex trials and have been unable to get an answer to one question. Hopefully, someone from this group will be able to give an answer. How is anticipated that Xiaflex will work? Is it expected to dissolved the scar tissue or does it just soften it or is there another mechanism at work?
Here's my understanding, based on its use against Dupuytren's contracture:
It's an enzyme that breaks down the form of collagen found in Peyronie's tissue. Its effect is local, and I think there' a possibility of damaging good tissue, so they can't just inject enough of it to spread out and dissolve all the bad tissue. Instead they'll inject small amounts of it into the bad tissue so it stays confined there. Beyond that I don't know what the plan is - I'm thinking there would be a number of injections, to break up enough of the collagen so that the bend is significantly reduced.
I hope the MD doing the treatment gives you a better explanation. In trials for Dupuytren's it was found to be safe and effective.
Encouraging news
I'm in the trials and have been injected. I'm fairly certain I got the real stuff. After some of the swelling and bruising went away there is definately improvement. The bend is reduced and the weak spot (dent) is reduced. I'm not 100% but back to what I would say is more in the normal range. I'll take it! I understand that if you improve past a certain amount the uro will not inject you again per the rules of the trials. I keep thinking the other shoe will drop and I'll return to the way I was, but I'm told it shouldn't.
If there are others at this point in the trails, let us know how its going. I hope we will be hearing other good reports. I'm thinking something really promising is on the way for everyone.
vernon21 - AWESOME!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! - SO WHAT IS THE DIFFERENCE YOU THINK??
Encouraging news to say the least! Could you also post a kind of time line so we can have a record of how long it was before changes were noted? For instance, days/weeks/months, etc. from injection to noticeable improvement or change. There's a couple of thousand guys holding their breath on this one here.
Great news vernon. I'm really pleased for you. Let's hope the improvements continue :)
Vern,
Can't tell you the how happy I am for you and for the rest of us. I have so much hope invested in Xiaflex. Keep us posted.
Greg
Angus, as I understand it, it works within days if not hours. For Dupuytren's they injected it, waited a little while and then tried to snap the cord on the spot by pulling the finger straight. In many cases that worked; if not, they waited a couple of days and tried again.
Guys,
I will definitely keep you posted. I will be going back to the doc soon to determine if I'm getting another round of injections. When you first get injected you are sore, a little swollen and bruised so it is hard to tell if there is immediate change. It was after a few days and a more full erection that I noticed changes for the better. I'll convey as much as a I can but don't want to do anything that might jeopardize my completing the trails. I have no idea how things are working for others and would like to hear. Things here look promising. Auxilium stock has really dropped lately so I wonder if its just the bad market or if there are other issues.
Like most everyone else here Peyronie's was a real psychological kick in the stomach for me. I'm fit and athletic and went from being proud of my old friend to being self conscious and unsure. So far so good with the trials, there is real improvement. Keeping my fingers crossed for everyone.
Hi.....
'Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product's use and effects'.......
Quote from: Dusty Letha on October 30, 2008, 10:05:57 AM
Hi.....
'Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product's use and effects'.......
yep, it's called off-label use. it's how most of us got prescribed pentox.
could anyone else with Xiaflex experience post something here.........
Iceman,I was screened yesterday for entry into the trial.The doctor told me that I was an excellent candidate.If the blood test and the EKG comes back ok,they will call me to schedule the first injection.I will keep everyone informed.
I went to my GP yesterday for my annual physical. He has become interested in the treatment of Peyronies Disease and is looking at this site. Small victory. He also was interested in my somewhat modest success via the VED. He also is going to stop prescribing vitamin E, Potaba and verapamil injections. BTW, he also is becoming very cautious with Flomax as a result of side effects. Apparently there are many including the ones mentioned on this board as well as some talk of arrhythmia.
We talked about Pentox and he is willing to give it to me for a few months as a trail. Before I start, I want to find out more about side effects. I checked out the various web sites but wanted to get feedback from real people. I am 64 years old and have a mild form of type 2 diabetes. Otherwise very good health, except for this darn Peyronies Disease stuff >:(
Does anyone think that Obama will be proactive in Peyronies Disease research???
Iceman:
I don't think that anyone really knows which way that Obama is going with the health care program in the USA. He has been all over the place with his ads about what he intends to do with the program.
Someone else in the States may have a better view point.
Old Man
I really don't think that a change in President is going to effect medical research to any great degree. Both candidates had promised to deal with health care issues, but I think when it comes to research, any real changes are going to be in the big hitter areas of cancer, heart disease, diabetes, etc. Peyronie's research is a back water. I suspect it will remain that way. The REALLY BIG risks to Peyronie's research are not political but ECONOMIC. If the US economy continues to go sideways, it could have dire effects on all medical research and could set Peyronie's research back years. Lets just hope that Mr. Obama can get things going again soon. That will not be an easy project, but he is a pretty sharp fellow and just might be able to pull it off. We can all pray that he will. - George
We all in the U.S. need to remind ourselves of our Jr. high school civics class. Presidents don't make laws. Congress does. The health plan may be influenced by a President but it will be developed under N. Pelosie, and H. Ried. Obama is unlikely to veto anything they send to him.
I'm expecting things to get worse. there is a wide ignorance of basic economics among the population and especially politicians.
Quote from: Iceman on November 06, 2008, 09:01:05 PM
Does anyone think that Obama will be proactive in Peyronies Disease research???
Only if he gets Peyronies Disease with a 90 degree bend to the right.
Sorry, bad political humor, but I just had to. Shame on me!!!
seaside2:
Don't be sorry. Ex-president Bill Clinton had a really bad and severe curve and did nothing about getting more attention drawn to medical help for everybody.
He could have gotten some research money and asked the medical community to advance studies, but didn't. Shame on him!!!!!
Old Man
I don't think President Clinton's condition caused any kind of dysfunction, didn't seem to slow him down too much anyway.
I agree that the biggest risk is that the economy will have more problems that take a while to fix. I'm personally hoping my penis will be injected with Xiaflex within two years, and hard economic times could definitely prevent that. Whatever policy is set out for, it will be executed the way Obama wants it. His popularity is overwhelming, and his party will do what he wants in Congress.
I just read that he may reverse stem cell research bans very soon. This is a great thing for all diseases looking at it from a long term perspective, but I doubt the short term benefit will be too great too soon.
i cant believe that there has been such a small response from people taking Xiaflex -
Cmon guys let us know whats happening with you ......!!!!!!!!!!!!!!!!
I'm in the trials and I have definitely made some improvement. I'm pretty certain I got the real stuff. I will be back to my uro soon for an evaluation and to determine if I will continue with another series of injections. I'm certainly not 100% but glad to be back into what I would call a more normal range. I've tried to be pretty objective and not overstate my results but I really think they could be on to something promising. I will keep you posted on where things go from here. I'm really hoping some good news is on the way for everyone.
thanks for that vernon21 - any other guys with xiaflex feedback - also if these tests work well what timeline are we looking at for public usage???
Quote from: Vernon21 on November 10, 2008, 12:22:48 AM
I'm in the trials and I have definitely made some improvement. I'm pretty certain I got the real stuff. I will be back to my uro soon for an evaluation and to determine if I will continue with another series of injections. I'm certainly not 100% but glad to be back into what I would call a more normal range. I've tried to be pretty objective and not overstate my results but I really think they could be on to something promising. I will keep you posted on where things go from here. I'm really hoping some good news is on the way for everyone.
fantastic. :) I'm kinda jealous.
I'm also more than just a little upset that none of the test sites are anywhere close to me.
Quote from: Old Man on November 07, 2008, 03:11:26 PM
seaside2:
Don't be sorry. Ex-president Bill Clinton had a really bad and severe curve and did nothing about getting more attention drawn to medical help for everybody.
He could have gotten some research money and asked the medical community to advance studies, but didn't. Shame on him!!!!!
Old Man
Old Man, where did you get this info re: Ex-president Clinton? Is that true??
seaside2:
I am a counselor for the ACS in my home town and as such have to be sponsored by a uro group. They refer patients to the ACS for counseling when needed.
One of the doctors in this group was a navy doctor/surgeon at the Naval Hospital in Bethesda, MD. While on active duty there he had occasion to examine the ex-president and he knew first hand the extent of the curvature, plaque and nodules, etc. He told us about this during one of our training sessions.
Old Man
Isn't that a breach of doctor/patient confidentiality or something?
jackisback:
Not if he did not actually say his name, but only referred to him with enough suggestions that we figured it out.
In addition, there have been other posts on this forum indicating the Pres. Clinton had Peyronies Disease.
Old Man
Actually, the issue of President Clinton having Peyronies Disease has been in the news in the days since the Monica caper. So it is definitely not secret information. In the midst of that kind of scandal, these kinds of things tend to leak out. - George
Gee, I was actually referring to Obama's politics and making a joke about anything that appears to be right wing, even his penis. At the same time, I strongly suspect that if he had Peyronies Disease like many of us do, he would be all over the funding issue!!!
Quote from: Iceman on October 26, 2008, 03:35:57 AM
does anyone think that this will work:
http://au.youtube.com/watch?v=dN6eAr92mRo
he says that it works for 8 out of 10 people...
I have actually written to Dr. Herazy on several occasions. He seems like an honest guy looking to help those of us with Peyronie's. I used his nutriceutical products aggressively. I have been seeing a slow change and improvement. The bend has decreased and distal rigidity has returned. I am going to continue this method of treatment so that I will be ready when Xiaflex comes out. I theorize that the surrounding tissue of the scar is invaded by collagen as well and taking the products he offers helps me reduce the total infiltration of the tissue. I will either get to a total cure by the time Xiaflex comes out, or I will reduce the scar to a very manageable point. My scars have shrunk.
Good to read about success with Xiaflex... I like most people will fly where ever I have to go to handle this problem.
Ted
Quote from: ohjb1 on October 28, 2008, 10:28:19 AM
I am going to be in the Xiaflex trials and have been unable to get an answer to one question. Hopefully, someone from this group will be able to give an answer. How is anticipated that Xiaflex will work? Is it expected to dissolved the scar tissue or does it just soften it or is there another mechanism at work?
So here is how I understand it works. Collagen that forms has cross links that draw the material together at a molecular level. Think of this product as highly specific meat tenderizer. It has a chemical reaction in the collagen that cleaves the cross links that cause the material to become this insufferable lump and allows it to soften/disappear. It is suggested by some literature that the enzyme is able to distinguish between the required collagen that deposits to fix an injury and the over expressed proliferation of collagen and fibrin that comes in a man with Peyronie's. I am very hopeful for this product. The literature and science behind it makes alot of sense. Floating around in the WWW is a video of a man getting injections into his hand for Dupuytren's Contraction. He is able to open his hand significantly after his Xiaflex treatment. I'm encouraged!
I come from a Pharma background and I know one thing that always occurs in a study is they set the bar as low as they can go for clinical success. They seek to "soften" the scar, not dissipate it. I suspect that the results from this therapy may exceed "softening" the scar. The video of the Dupuytren's patient describes a full rupture of the nodule and a return of the hand's flexibility after physical therapy. It may be that the stretching techniques along with Xiaflex along with the appropriate oral therapy to clean up the remnants of collagen after Xiaflex does its things will be a path to success. That is what I am going to do the minute Xiaflex is out.
I am a fan of Dr. Herazy as well. I write to him and have had success using his suggestions for Oral treatment. I believe it works from my own experience. While I am not cured, I am encourage.
I pretty much agree with Ted's observations regarding Xiaflex and how it works. Thanks Ted for that contribution! In many cases it is just a matter of breaking a single metabolic logjam and from there on the body is able to resolve things itself. The hard part is identifying the logjam and finding something to target it. It really sounds like Xiaflex is a winner in this regard. Already I am hearing of increased investment capital becoming available as potential investors are starting to get excited about the prospects for Xiaflex successfully treating Peyronies. I think that is pretty amazing in and of itself. - George.
Ted
Could you please post which kind of oral treatment Dr. Herazy suggested to you? It may be of help even for others here in the forum!
Thank you in advance!
Cheers
Ok, so I know this is simple, since there are trials now for Xiaflex (peyronie's) in Phase II, those are the Phase II trials, yes? And then would there be Phase III trials after that? And how difficult would it be to get in on those trials?
Xiaflex for Dupuytren's is currently due for release in 2009 according to some news from google. Ah, if only we could get some black market Xiaflex :)
I heard that if Xiaflex is released in 09 for Dupuytren's some doctors will most likely use it for Peyonies as an "off label" use.
where did you hear that???
Hey folks: Here is the break down of the phase trials.
Phase I is designed to assess safety and tolerability of a drug. In this phase they make sure the drug doesn't kill anyone and they figure out what the range of a dose is for efficacy and tolerability. Basically, how high can they go before they kill'ya.
Phase II is designed to assess if the drug works. Safety is further assessed.
Phase IIA is designed to determine dosing.
Phase IIB is designed for efficacy at specific doses.
Phase III is a randomized double-blind study for efficacy in comparison to the standard of care. In the case of Peyronie's, there is no real standard of care for which you can compare. If you were studying headache medicines you would compare it to aspirin.
So phase III will be another study that will compare to another therapy. It will absolutely include the exact same dose and protocol that the Phase II, Phase IIa and Phase IIb studies included for all patients that were injected with Xiaflex. That way, when the studies are done, they can say, "We've injected " +/- 10,000+ men and we get SUCCESS!!!" It is part of the strategy of setting up your future marketing so you can maximize success. This is a business. So basically, when they show success in the Phase IIb, they will immediately start a Phase III that takes almost the exact same time as Phase IIb takes to complete. Why? Because they will just do the exact same thing again, except this time they will have the standard of care, in this case, maybe a verapamil shot, or maybe a saline shot followed with an oral dose of vitamin E and then they will compare.
To answer "IceMan's" query... Doctors can ABSOLUTELY prescribe medication off-label for a condition. The drug companies just can't market it for such use until it has been approved. It is a delicate dance. Doctors will frequently prescribe drugs for something that has absolutely nothing to do with the indication... that is how doctors are injecting Peyronie's plaques with Verapamil. So I believe that once the Dupretyne indication is passed, then I will run, not walk to any doctor who's name is published on studies for Xiaflex and Peyronie's disease and say, "ME FIRST DOC!!!" But I am aggressive that way.
didi20031 remind me to give you the regiment I used for treating Peyronie's with neutraceuticals... It is just late and I'm going to bed!
ted williams - when do you think we will be able to approach these doctors - what time frame at the earliest would this be possible in your opinion - can we just ring up a doc and make an appointment??
Ted, Dr. Herazy is a big time proponent of Neprinol. This is a very expensive product and Dr. Herazy has a financial interest in selling it, although, I have to admit his margins on other products have been very reasonable. But I am really very skeptical of Neprinol in terms of potential benefit for Peyronies. I took it for quite a long time with no perceived benefit. But I would be interested in knowing if you took it and felt you were getting some benefit from it. So far, I have never heard anyone provide credible first hand testimony as to Neprinol providing any Peyronies benefit. - George
Should Xiaflex become available in 09 and used for peyronies on an off label basis, the skill of doctor doing the injecting is every bit as important as getting the real drug. Remember this stuff dissolves tissue. A skilled uro and expert in peyronies that knows your specific tissue architecture as well as where and how to inject is vital. If I've learned anything from being in the trails that would be at the top of the list.
For George999 and didi20031:
My experience:
I understand anyone's concern that the treatment suggested comes from a person that is making money off of the sale of the products. I am of the mind that no one does anything unless they are getting paid. When I have corresponded with Dr. Herazy, his responses have been from a place of personal experience. I believe him. I am in agreement with the philosophy he suggests. My Peyronie's took about 2.5 years to become what it was. After 6 months of treatment with his therapy, I have seen it recede noticeably. I have seen the plaques soften. I believe it will just take time to get the progress I seek.
Dr. Herazy has a web-site where you can read a lot about the "WHYs" of this treatment.
See his web-site: http://www.peyronies-disease-help.com/index.html
Morning: Empty Stomach
2 - Nattokinase.
2 – Fibrozyme
Morning: 1 hour later with food
1 Vitamin E. 400/400
3 PABA
Afternoon: 1 Hour at least before lunch or 2 hours after lunch.
2 – Nattokinase
2 – Fibrozyme
Afternoon: with food.
3 PABA
Dinner: Empty stomach. I usually take it a few hours after eating dinner
2 – Nattokinase
2 – Fibrozyme
Evening: with food
3 PABA
1 Gamma E 500.
I have taken Acetyl-L-Carnitine in a 500 mg capsule
2 tablets in the A.M. with or without food, it doesn't matter.
2 tablets in the P.M.
This is the most expensive of the bunch and I backed off taking it just because it cost so much, but I really should put it back into my routine.
Vernon21:
I couldn't agree with you more regarding the choice of doctors for this Xiaflex procedure. I have found video of patients receiving verapamil injections. I can only imagine that in the wrong hands, a doctor could devestate one's progress. Since you are in the trials your experience and opinions are very important.
How are you doing now Vernon21? Are you still feeling progress? I am very curious to learn more about your progress/concerns/success.
Thanks in advance for sharing your experience.
Iceman,
You asked when I thought this treatment would be available even off label... I just don't know. I just keep checking in on the company's web-site to see what the progress is. The approval process is long in the FDA unless Auxillium can get an "orphan status" for their product. This is when the treatment is the only treatment for the condition. It might be that they will get that status.
Like you, I am waiting.
Ted
Thanks a lot for the interesting and detailed post. Maybe I will give it a try, if I can get nattokinase in Austria ??? The only thing is that I don't want to take PABA since my stomach is very sensitive (I have to avoid even things like coffee, onions etc.) and PABA is known to cause GI upset.
At the moment I am on Vit E, pentox, acetyl-L-carnitne and L-arginine.
Best wishes!
Hey didi, (George, see a follow up for you as well.)
Too high a dose of vitamin E gives you the shits, if you don't take the PABA with water on a full stomach you do have acid burps. I worked out both of those for my constitution and I was able to find acceptable, tolerable levels for both. What I really found was that progress was determined by the softening of the tissue that made up the scar. That is where I am at now.
Most importantly, I try and avoid the negativity that comes with this condition. The mind-body connection is real. People do recover from this. Good health, good nutrition and a good out-look can only help in the healing process. I now live a very, very healthy life-style. Little drinking, no smoking, elimination of white sugars, lots of leafy greens, and lots and lots of exercise. My attitude is that I will over-come this condition. My expectation is that Xiaflex will help.
To follow up with George: I believe it takes more than just Neprinol to make progress. You have to get the enzymes to the site of the injury, and you also have to get your vascularity improved. Nattokinase improves vascularity. I would even include a little baby aspirin on a full stomach to get my blood flowing at a peek. (If you nick yourself shaving however... it takes some time to stop the bleeding.) On top of all of this is managing inflammation that is associated with the condition. The synergistic effect is a result recognized through-out pharmacology. Some drugs, in combination dramatically enhance the ability of other drugs to work. Dr. Herazy's theory is that it is the same for Neutraceuticals in the treatment of Peyronie's disease.
Take the time to ready Dr. Herazy's web-site. If the philosophy makes sense to you, do it! What do you have to lose, money? I'll toss some cash at a chance for success. If it doesn't work, no harm no foul... I live to earn another day.
We could choose to be negative and seek failure, or we can be positive and seek success. I want SUCCESS!!! But that is just the way I am with everything.
Regards,
Ted.
Quote from: Ted Williams on November 17, 2008, 12:28:44 PMTo follow up with George: I believe it takes more than just Neprinol to make progress. You have to get the enzymes to the site of the injury, and you also have to get your vascularity improved. Nattokinase improves vascularity. I would even include a little baby aspirin on a full stomach to get my blood flowing at a peek. (If you nick yourself shaving however... it takes some time to stop the bleeding.) On top of all of this is managing inflammation that is associated with the condition. The synergistic effect is a result recognized through-out pharmacology. Some drugs, in combination dramatically enhance the ability of other drugs to work. Dr. Herazy's theory is that it is the same for Neutraceuticals in the treatment of Peyronie's disease.
Ted, Actually I was taking natto along with the Neprinol. The Neprinol really cleaned up my lungs and seemed to be helpful for my joints as well. But no discernible effect on the Peyronies. But I most certainly agree with you on the point of managing the inflammation. I strongly consider that to be the number one issue at hand. Basically all of the other stuff you were taking (other than Fibrozyme (the original Neprinol) and PABA, I have also taken and found to be useful. (If you scan over my past posts, you will see a lot of familiar products.) And although I have never actually used PABA, I have always suspected it might be helpful in dealing with Peyronies. I actually have an unopened container of it lying around. That is how close I got to taking it. Right now I have other fish to fry. I was taking melatonin to help in lowering my blood pressure and got an inflammatory reaction to it. So I am dealing with inflammation big time now. The thing that is really helping me with that at this point is artificial sunlight, full body, for 20 minutes a day. And it has had the effect of shrinking my inflammatory plaques rather dramatically in the process. Most of the other stuff I have quit since I don't want anything to aggravate the systemic inflammation (ALC, interestingly, was doing that, although it was helpful with the Peyronies). But I am continuing to take Pentoxifylline which is a major anti-inflammatory drug. But your points are really interesting and an extremely useful contribution to the discussion here. - George
Quote from: Ted Williams on November 16, 2008, 10:10:21 PMTo answer "IceMan's" query... Doctors can ABSOLUTELY prescribe medication off-label for a condition. The drug companies just can't market it for such use until it has been approved. It is a delicate dance. Doctors will frequently prescribe drugs for something that has absolutely nothing to do with the indication... that is how doctors are injecting Peyronie's plaques with Verapamil.
Thanks again for this reply Ted. This raises something very interesting which I was not aware of. You are sure that Verapamil is only administered to the penis as an off label function??? I was previously unaware of this. My thoughts on off-label consumption has always been that it could only apply to oral medication. Since one group is using the medication for a different purpose, it doesn't matter in terms of side-effects, because both are taking the same medication the same way. However, I did not know that off-label drugs were allowed to be applied in different ways! Just because a drug that dissolves collagen is approved for injection into the hand would
not take into account the very different potential side-effects of injecting into the penis. However, if you say that it was done before with Verapamil, then this is a really great precedent. If I found out that Xiaflex treatment would be available as early as 2009 off-label to the general patient.....well that would be the only Christmas present I need for this year and next.
To Vernon: you said that you had specifically heard that Xiaflex would be offered off-label. Where did you hear this, I wonder? I know you are taking part in the trials, so you can understand it makes a big difference if you actually heard this from someone involved in administering the medical trials, or if you just heard some speculation on the internet.
Jackisback,
I heard it from my doctor who is preforming the injections. He is one of the top professionals in this field and an excellent doctor. I will share more as soon as my trail is over. It is my understanding that injectable drugs are also used for off label uses. Botox originally had a different use and currently Gardasil is approved for women but it is being given to men as an off label use (the drug company is now working hard to be able to market it to men).
As I said before, if Xiaflex becomes available for dupuytren's in '09 DO NOT run out to any doctor that will inject you on an off label basis Remember this stuff dissolves tissue! I have learned the skill of the doctor doing the injecting is just as important. He must be experienced, know how your specific tissue has formed, and where and how to attack it. My doctor had used Collagenase in the past and knew what injection points would have the best effect for my situation.
As for my trials, I have had another round of injections. The swelling and bruising has not totally gone down yet, but I am very encouraged. I will share more once I have a better idea of the results. At this point I don't think there is any way I received the placebo.
Did he seem to imply that it was a sketchy deal that less ethical doctors would start injecting it, or did he imply that the doctors in the top of their field would inject it (i.e. himself and the other doctors picked for the trials)?
Yeah, I definitely wouldn't do it unless I could get it from one of the well known, reputable Peyronie's doctors. Hopefully those guys will not be unwilling to do it!
Jackisback,
He did not say but my guess is that since he and others effectively used Collagenase in the past that top doctors in the field would not have reservations about using it as an off label use. I don't think the use of drugs on an off label basis by informed experts is viewed as questionable. I won't see him for a few weeks but I try to make a point to ask. Again, this is only a guess on my part.
does anyone really think that xiaflex will happen or do you think that we will be back here in 12 months talking about it like with every other new whizz bang treatment or cure thats discussed - if its sooner and does work by some miracle , how does someone not living in the USA get there hands on it
perhaps you need to travel to the USA.
Regarding Non-U.S. patients:
If you are in a European or westernized country you will likely be able to get the treatment. The profit indicators for Auxillium require a world market to hit there expectations. European clearance of new drugs is easier than the FDA. It is possible, that if you are European, you will get the treatment before your U.S. counter-parts. As for the validity of this drug, phase III of the approval may reveal something in the safety profile that will cause the drug to be withdrawn from the process. That being said, the business indicators suggest that Auxillium is making swift moves to launch this drug immediately when it is approved. Keep the faith, their stock is up, their moves indicate launch, their studies show success and the patients are now starting to say, "Not Bad!" It is all good.
All indicators suggest that this is not a bunch of bull.... It is the real deal.
Regards,
Ted.
I agree. I think they are on to something and will push hard to get this drug available world wide as soon as they can. We should remember it has already been used successfully in the past.
Is Xiaflex supposed to work even for calcified plaques?
I read online that two disqualifiers for people on trial where those that:
a) could not maintain an erection, and
b) those whose scares and calcified
I think the information was on Auxilian's homepage though I am not an expert, and am guessing others may be better informed than I.
Hello Bluth:
Xiaflex is a Collagenase. It is an enzyme that digests collagen deposits. We have collagenase naturally in our bodies. It does not digest calcium. Though I would not exclude the idea of Xiaflex as part of an over-all treatment for Peyronie's Disease. Often times, the entire plaque is not calcified. I hope this is helpful.
Regards,
Ted.
I am bumping this up because of no response. Perhaps because it was somewhat buried in my post.
In any case, are there any side effects to Pentox that I need to be aware of?
We talked about Pentox and he is willing to give it to me for a few months as a trail. Before I start, I want to find out more about side effects. I checked out the various web sites but wanted to get feedback from real people. I am 64 years old and have a mild form of type 2 diabetes. Otherwise very good health, except for this darn Peyronies Disease stuff >:(
Quote from: Ted Williams on November 20, 2008, 10:45:15 AM
Hello Bluth:
Xiaflex is a Collagenase. It is an enzyme that digests collagen deposits. We have collagenase naturally in our bodies. It does not digest calcium. Though I would not exclude the idea of Xiaflex as part of an over-all treatment for Peyronie's Disease. Often times, the entire plaque is not calcified. I hope this is helpful.
Regards,
Ted.
So in laymen's terms. Xiaflex can help people who have had Peyronie's for years or not?
Here is a link that Xiaflex may not be useful against calcified plaque's. http://www.curepeyronies.net/index04Xiaflex.html (http://www.curepeyronies.net/index04Xiaflex.html)
QuoteThere will be at least 2 screen out criteria. 1) Calcification of the scar tissue
area and 2) Failure to achieve an erection via injection. This criterion makes
sense because calcification or hardening of the area will make it more difficult
for Xiaflex to soften the plaque.
Quote from: seaside2 on November 20, 2008, 11:44:09 AM
I am bumping this up because of no response. Perhaps because it was somewhat buried in my post.
In any case, are there any side effects to Pentox that I need to be aware of?
We talked about Pentox and he is willing to give it to me for a few months as a trail. Before I start, I want to find out more about side effects. I checked out the various web sites but wanted to get feedback from real people. I am 64 years old and have a mild form of type 2 diabetes. Otherwise very good health, except for this darn Peyronies Disease stuff >:(
Just always remember to take it with food. If you don't it will give you some stomach upset and queasiness. Other than that I have had no problem with it. - George
George999
Xiaflex should be considered for long-term Peyronie's. So long as there is collagen present in the plaque, then Xiaflex stands a chance of disolving that plaque.
Regards,
Ted
Ted, Concerning Xiaflex, I believe that Xiaflex may prove to be quite useful. But at this point, Xiaflex is not approved for Peyronies. Until it is, I would not recommend it. The problem with injectable drugs is that success or failure often rests on the skills of the doctor or technician administering the injections. I have known people who got pretty messed up with injections of cortisone, for example, simply because the doctor didn't know what he was doing. I can't even imagine all of the things that could go wrong with something like Xiaflex. I also want to see a long term track record on it first. - George
Bluth,
Auxillium choses the screenout criteria they do to maximize the potential of the trials. You must have a 30 degree curve to participate in the trials. This is not because people with small degrees have worse Peyronie's beyond the hope of being positively effected by Xiaflex, but because the drug is more likely to have a greater impact on the change in degrees as well as change in percentage of degrees of the penis after treatment if you started out with a larger deviation to begin with.
In the same vein, calcification is something they feel could make their numbers less impressive. They clearly feel that Xiaflex could be less effective against calcified plaques, but I doubt there is anything to suggest that it would be useless. And in fact, maybe some of the more scientific minded on this forum could back me up, but I believe it is hypothesized that calcification could even be reversedwith this drug.
Seaside, yes people do report various side-effects. None too serious that I know of, I've only heard of relatively minor things like acne and acid reflux. But this is a prescription drug, and given your Diabetes I would think you would like to clear it's safety with the doctor potentially prescribing it to you.
Thanks Ted and Jackisblack. Great answers as usual.
Ted,
I agree that it is an absolute must to see a skilled doctor that is very experienced in injecting Xiaflex for Peyronie's (such those selected to use it in the trials). However, if Xiaflex was approved for another use before it is for Peyronie's, I would not hesitate to see one of those same highly qualified doctors if they would use it to treat Peyronie's as an off label use.
Strong point Vernon:
No rookie doctor is getting near me and mine. How is the progress going? You had your second injection, right? Have you felt the plaques subside? Has your curvature changed? Your updates are appreciated.
Regards,
Ted
Hey Vernon:
Any updates on your progress?
Regards,
Ted.
I am in the Xiaflex trials and have received 2 injections which completes my 1st of 3 treatment cycles. It has been 2 weeks and no change in my condition. Does anyone know if prior use of Xiaflex treatment has resulted in immediate change or was there a threshold point at which point a series of injections over time caused an improvement?
ohjb1:
If the trials are a double blind study group, it is possible that you are getting a placebo instead of the"real" stuff.
Old Man
The good news for ohjb1 is that, as I understand it, if you end up with a placebo in a study that turns out to be successful, you end up first in line for the real thing at the completion of the study. - George
George - I wish you were right, but as it turns out this is not the case. This is discouraging
ohjb1 - whats discouraging - that its not working or that you are not first in line?? - if its not working thats absolutely BAD NEWS - and good news I guess if you are on a placebo - at least theres a bit of hope here...
Hey ohjb1,
Stick with the study. Yes, most folks that have been in the study have experienced immediate results. Most notably, those being treated for Dupuytren's contraction have had immediate, noticeable changes in their condition. It is likely that the doctors are not allowed to disclose anything regarding the trial and as it is a blind trial, they don't know if you are are receiving placebo or the real thing. In most cases, when a study is done and success, along with safety, is obtained, they do an open-label portion of the study. This is designed to show that the placebo patients, after failing at placebo, have now achieved success with the real drug. It is a good piece of marketing that increases the number of successes in the trial and allows them to file it all together with the FDA for all of their future marketing material. It just looks "sexy" to market a product that takes a failure and turns it into success. Next, when there is a drug that represents the only certifiable treatment for a condition, then there is a duty for the doctors to then apply it to the placebo patients. This is common in life threatening situations and may even apply in this situation.
I appreciate your discouraged attitude. I wouldn't want to go through what you are going through. Be encouraged that others are reporting success and that past studies in Dupuytren's and in Peyronie's have shown success. If there is absolutely no change in your condition, then you are likely receiving placebo and it is likely they will want to include you in an open-label portion of the study.
No matter what... Stick With The Study! Don't become "Lost To Follow-Up." They don't call you when it is time to get the real thing if you are "lost to follow-up".
Regards,
Ted.
To iceman - what is discouraging is that even if I (and the other 25% of trial participants) go through the entire trial and it turns out that the placebo was administered - the company will not offer Xiaflex.
To - Ted Williams. I have been advised verbally and in writing that Xiaflex will not be offered to those individuals who receive the placebo. Therefore, what you have said in your recent email can not come to pass unless the company decides to change its policy.
ohjb1, You have to realize that they may be required to tell you that for legal reasons. Life is full of these kinds of situations. I really don't think that this means that they will actually not offer it to you. I think that this means that they want to be legally clear of any implied obligation to offer it to you AND that such an offer may be contingent on your remaining for an extension of the study. A lot of this stuff is what is known as legal "boilerplate". Its intention is to protect the company in question in all circumstances and it indeed does not preclude the fact that they can change their policy later on down the line. I think you should hang in there and hopefully these issues will all be worked out in the end. - George
Thanks for your comments and words of encouragement. In about a month I have to go back to the urologist and undergo some tests that will objectively determine whether or not there has been any improvement. Will get back to you then. Thanks again.
Dear ohjb1
I cannot find a protocol for the trial that says whether or not there is an open label follow-on study that will follow the double blinded randomized clinical trial (RCT) for Xiaflex.
But, I want to put in a plug for good science right here and now. Even if you got placebo, and they do not do an open label study that gives you free drugs soon thereafter, your participation in this important research will help all of us soon find out if this is a viable treatment or not, and make it possible for this drug to come to market - where you and I both could benefit from it. You may end up being able to get it as a regular patient, and not in the study - but that will still happen because you were willing to participate in the research.
For that, I am grateful.
Tim
Hi all,
I haven't been on in a while, but I saw some ruckus in another thread that briefly mentioned pirfenidone, which somehow I'd never heard of.
Anyways, for those who haven't heard of it, here's a very short (good for me) and interesting blurb. It's recently been approved in Japan, and it's on "fast track designation" in America.
http://www.bizjournals.com/sanjose/stories/2008/10/13/daily72.html
I must be missing something. Auxilium will not do anything for study patients who received a placebo? You're supposed to make all those trips and appointments at your own expense, and undergo an uncomfortable if not painful procedure - for nothing? Or do you get a nice handshake at the end?
This isn't how I thought it was supposed to work.
j:
Now you know why I don't participate in studies of any kind.
Old Man
J - i don't get it either.
You would think they would at least offer the drug to those who received the placebo and have completed the study. Those who complete the study will receive $250 from the drug company.
From what I can tell (and I maybe wrong) they do not have a great deal of patients signing up for the study.
I still encourage those here to participate in clinical trials if offered the chance - it is the only way that science will move forward.
Most studies reimburse one for travel and/or pay them something. A too large of a reimbursement is seen as coercive.
Tim
I didn't know about the $250. It's not a lot, but it's something. It wouldn't be enough to get me to jump through all those hoops without knowing I'd get an actual injection of Xiaflex at the end.
No doubt it was a simple financial calculation for Auxilium. It pains me to say I hope they succeed; because if they don't, we start all over and that means another 10 years.
I recently participated in a study at a nearby university for which I did an interview, had an MRI and was given $50; I'd have done it for nothing, and I may do more. But what Auxilium is asking is, well, a bit less pleasant. And they're expecting to make a lot of money.
Hello,
First time I'm posting here - have been following the discussions on this board for a while, and want to say I'm very impressed with the quality of the discussion that goes on here.
What's prompting me to post now is the discussion about whether the latest Auxilium trials will include treatment for those men who fall into the placebo group.
I've just signed up/been screened for this study, not yet been treated, so I want to be circumspect in my comments - don't know how much comment is permitted by people participating in the study, and don't want to do anything to jeopardize my participation.
Anyway, the physician and his research coordinator both told me verbally that everyone who gets the placebo in this trial, will then be offered the real treatment, at the end of the trial, free of charge or course.
Also, in the written consent form I had to sign, it said that if you are in the placebo group, at the end of this study, you will be offered the chance to participate in a further study.
So yes, it will be a pain if I end up in the placebo group, but my understanding is that I'll get the treatment either way, either now or later.
Not sure why different doctors might be communicating a different message. It would be worth re-checking the consent form you signed; it should be the same for all the different study groups.
Again, just want to express my appreciation for the good work people are doing on this forum.
G.
Quote from: j on December 05, 2008, 12:14:12 PM
I recently participated in a study at a nearby university for which I did an interview, had an MRI and was given $50; I'd have done it for nothing, and I may do more. But what Auxilium is asking is, well, a bit less pleasant. And they're expecting to make a lot of money.
Who cares? I'd gladly do it for free if there were a location near me, if for no other reason than to do what I can to get this treatment to market. I simply cannot fathom the mindset behind refusing to participate in the study because you might get the placebo, or you might not get the actual drug if you are given the placebo, or they're not offering enough money. It just seems so completely contrary to your own interests to not participate if you qualify, and there isn't an undue travel burden.
I turned 30 this year, and peyronie's has been affecting me since I was 22. I'm sorry, if I sound somewhat bitter, but when almost a third of your life has been jacked up because of this, and a solid half of your sexual life thus far has been negatively affected, my sympathy levels are pretty low for anyone in a position to move the process along but don't because of what ifs and maybes.
Cry me a F^@$!ng river about maybes and ifs about placebos and not being paid enough. Let's have just a little bit of self serving altruism and get the damn thing to market and in the hands of our doctors so we can all be treated if it's shown to work.
Jon - speaking of cry me a river. You are big talker, but apparently you didn't try to get into the study. I live quite a ways from the study site and am traveling there, also require at least one overnight stay each time.
What has stopped from enrolling in study? I believe there are still open slots at some centers. When can we expect to hear your updates from study participation?
jon:
If this means anything to you, I have had Peyronies Disease for over 55 years now. So, I admire your position about studies, but they are just not for everyone. I have tried to get into several study groups without success. There was always some little something the leaders/companies wanted that I did not qualify for, so good luck to those are interested and can become part of them. They are just not for me, especially at my advanced age compared to others here.
Old Man
jon, you're basically right. If I looked at it purely logically I'd have to agree that it would be to my advantage to participate on any terms. What annoyed me was the fact that Auxilium is a very well-financed for-profit company that clearly can afford to give a real injection to every patient. And according to G. that's what they're going to do, so my previous comments are moot.
j:
Another aspect of any study is to get FDA approval of the product, there has to be volumes of paperwork, laboratory reports, results of those with the actual medicine and those who took a placebo. All of this eats up capital and resources, so the companies have to be careful of what they do, etc.
I know first hand about production of a product as part of my career was with an aircraft engine builder.
They sold engines to the government and you would not believe the paperwork, trials and tests that we had to do just get their final approval.
Just my 2 cents.
Old Man
Quote from: ohjb1 on December 05, 2008, 03:33:26 PM
Jon - speaking of cry me a river. You are big talker, but apparently you didn't try to get into the study. I live quite a ways from the study site and am traveling there, also require at least one overnight stay each time.
What has stopped from enrolling in study? I believe there are still open slots at some centers. When can we expect to hear your updates from study participation?
cost prohibitive. I'm in DFW. Show me a study location within a 10 hour drive of me, and I'll be there. I looked into flying to SF, Chicago, Norfolk, Miami, Hartford, etc.. and I'm looking at a minimum of 300/rt + hotel+ car rental. Now I don't know about you, but I don't have that kind of money to shell out every 6 weeks. If I did, again I would be there. The only thing preventing me from enrolling is cost. Which if you read what I posted, I quite clearly said "if you qualify, and there isn't an undue travel burden."
But like I said, show me a study site within a 10 hour drive of me, and fwiw I can make it to Birmingham, AL in 10 hours, and believe you me, I'll be there.
I just double-checked the wording of the consent agreement, and I was partly wrong: it says you "may" be asked to be in an additional study - it doesn't say "will" - I guess there's a world of difference between "may" and "will"!
In my case, the doctor and research coordinator were very emphatic that I would get the treatment no matter what - and I've known this doctor for a while and trust him, so I'm going to go with that. Plus, I haven't even had a treatment yet, and if I'm not in the placebo group, then the issue will be moot for me personally.
I don't know anything about clinical trials, and thought they had to be done consistently, but in this case, it sounds like they may be funding some doctors to give further treatment to the placebo group after the completion of the study, while not funding other doctors
So ohjb1, sorry to say you may be right, if you have it in writing from the doctor and Auxilium that the placebo group doesn't get further treatment.
This is complicated - on the one hand, I think it's wrong if some placebo patients will get further treatment, and others won't - particularly if this is being done to save $$. On the other hand, clinical trials must be very expensive, and we all have a vested interest in Auxilium surviving so that this treatment (if it works) gets to market. If I'm reading their financial statements right (and I guess my reading skills are now in question), they have yet to record a net profit, so they are essentially burning funding - and not every start-up company survives, even if they have good products.
I also think it's important to try to help others by participating in the study, but I don't have to incur the expense of flying in, so it's easy for me to say.
It still comes down to a personal decision whether or not to participate.
Good luck.
G.
I'd like to add a mea culpa:
The last time I check clinicaltrials.gov, there was no site close to me. There is now one in Houston. I'll be calling Monday.
Hello folks,
Regarding those concerned about whether a man will receive Xiaflex after the study if they are in the Placebo group; I feel confident it will be so. Everyone, put your "Cover-Your-Ass-Hats" on. The difference between "you will receive Xiaflex" and "you may receive Xiaflex" is about liability. No study would guarantee the out-come such that they would confidentally offer the product to all participating. Patients always respond differently to things and if you happen to be an unfortunate placebo patient who also develops severe side effects as a result of the injection itself, then it is highly unlikely that you would be called back. If the needle is bad for you then the study is not serving you well by guaranteeing that you also get the product.
This study is being designed for success. Typically, in a study like this the design will be 2:1. This is 2 Xiaflex to 1 Placebo. This product has been projecting success for a long time in all of the previous studies. The best way to raise capital for a company is to put some bright hope on the Horizon. Xiaflex is that and will transform this company if successful; when successful! To maximize the show for the FDA and for the investor public, creating a "success narrative" by showing how previously failed patients responded to the treatment is an ideal way to market the product while fulfilling the requirements of a double-blind-randomized placebo controlled study.
As for the $250 and what Auxillium should or should not pay you, this is another liability thing. If they paid each patient a sizable sum, then it could be viewed as an intrusion on the study. Its like paying people to donate blood. Pay for blood and you get junkies saying they are virgins that never booted black tar heroine with prostitutes. If you make the process lucrative, then you may get folks entering the study that are guided by less altruistic motivations. I'm not saying they would inflict themselves with Peyronies, but they will lie about anything subjective that makes a requirement to enter or measure the study.
Stay confident and "STICK WITH THE STUDY!" Lost-to-follow-up patients don't get to be considered for the open-label portion of a study.
This is a great product on deck. It has a strong chance of meeting all the requirements FDA approval. We will likely all be taking this injection.
Best wishes,
Ted Williams
Ted - the study design is 3:1. I don't think the $250 is an issue for anyone.
Hello everyone! I am a 17 year old male living in Glendale Los Angeles. I didn't see a introduction forum. Would be good to have one to help introduce all the people that are newly diagnosed. I'f you do have one sorry just didn't see one. I have been living in hotels with my father for the past 4 years so money has been tight. I had to go to the local free clinic. They setted a appointment up for the sylmar hospital to have a urologist check me out. I't took a long frusterating wait but eventually I got in. He was UCLA doctor that volunteers on his free time for the people who can't afford urologist. I was having a lot of issues with my pee being blocked and coming out irregular. i also have a very low output of pee. pee little bits and sometimes i have to flex my muscle to get the rest out. even doing that i feel burning in my penis like the pee isn't coming out and is stuck in there. I was also having a lot of issues with my erections curving left and downward. He checked me out and said he could see nothing wrong except for the penile whole looked small so it was blocking my pee. I was acourse angry cause my penis was destroyed and this guy was telling me there was nothing wrong with it. I'm 17 and I haven't even been able to get a hard on in the past 2 weeks. It's very uncomfortable flacid and is always hard. Sometimes it bends to the left and then even to the right less often. So we decided to go to Healthy Kids to help me out. They got me into a Urologist last night. He was a good one from USC and he did a thurough but painful examination. Also pushed back up my hemoroid. That wasn't so pleasent haha. He confirmed my worse fears. I have Peyrnoies disease. I am only 17 so I must be a very rare case right? He told me it wasn't from injury but I think he was just trying to be nice. I had a lot of mental depression and basically I physically destroyed my penis beyond the limit. After I masterbated 5 times one day I felt a very sharp pain. I was already having problems with the Peyrnoies but I made it a lot worse that night. Even after my erections were massively curved, painful, and even short I still continued to minupulate it and saw the resolts. It just got worse everytime I pushed my figurouse masterbation. I think I was kind of torturing myself kind of like what cuters do. I didn't enjoy the painful masterbation but I didn't care I just wanted to get off one more time. Sex addict to my hand for sure. Now I haven't masterbated in maybe 3 weeks. Experienced some painful pre mature ejeaculation wet dreams twice. I haven't even had a errection once yet other then those wet dreams. I am 17!!! this is insane =( Now im ready to recover. Im quiting cigs and im going to start working out everyday! I need as much as help as I can get. Please guys realise my agony and do everything you can. I love you all for being so strong and living with this. This disease is truely a tough thing to have to live with but Im happy to see many people can being strong and fighting it! So can you guys please help me out with this? Im so young and ive been through nothing but misery my entire life. I use to live in a happy mansion in Agoura Hills untill my parents broke up. Found out my mom was scitzophrenic bi polar. Dad lost his job at Guitar Center and we lost our house. Me and my sister moved in with our dad. Now my moms homeless. I got out of juvy from a crime and drug past 2 years ago. I thought I could change my life around. I have always had problems with masterbation. I started when i was 8 humping the floor. When i got a girlfriend when i was 14 I tried to have sex but couldn't maintain a errection because i was masterbating none stop everyday. I tried to have sex with her again and I failed. Ive tried to have sex 2 times after that and I failed again. 4 times I have tried to have sex from age 14 to 17. Now I have this! I am a atractive guy and have a lot of friends. Life is getting to hard to bear anymore. All these beautiful girls I want I cant have. I need to fight this guys! Will you guys promise to help me? Ill do anything to be happy like I was when I was a kid.
I just wanted to put up a post about randomized clinical trials (RCT) and how they are designed. RCT's are not done to "help people", they are done to prove if a drug is going to be able to help anyone at some point down the road.
First, the design has to be done to detect a difference between a drug and placebo if one actually exists. This is not so simple. For instance, testing drugs on someone who is barely bent, or so severely bent, that he falls outside the "normal" range of usual Peyronie's, means that an improvement may be impossible to see. If, for example, I entered a study and had a 15 degree bend upwards and dents, then how are they going to measure "improvement"? Less dents? How will they quantify that?
I have seen pictures of improvement from treatments for Peyronie's and thought that there was NO difference even when they claimed it existed - it looked like faulty measuring technique. What if I am not as hard? Will that lead to a difference in angulation? This study shows "improvement", but when I look at the measures, I see some variability in how they measure the angle of deformation, and it also looks like the patient is not as hard for the "after" shot.
http://www.scielo.br/scielo.php?pid=S1677-55382004000300004&script=sci_arttext
So coming up with rigorous methods for selection of patients, and for ways of measuring progress is vital to doing a good study. Old Man may have been ineligible for studies in the past because of another medical problem, or the degree of angulation - there are lots of reasons that folks are excluded from studies.
Almost all important studies have follow-on studies called "open label" that give all patients a shot at real treatment. This is not done if the first part shows no benefit - hence the disclaimer "may participate" in future studies. Also, if you had an adverse event, or if your penis changed shape for other reasons, you might then become ineligible for study. You can NEVER guarantee participation in a follow-on study. It was my understanding that Auxullium was planning to do an open label study after the initial study; they did that for their DP studies.
My point is that we should be trying actively to participate in drug trials. All of us can decide for ourselves if we want to participate in any particular study. I will not do Xiaflex because I do not have heaped up plaque, but in stead have dents and small areas of fibrosis and contraction. I am also very uncertain that an injection would be good FOR ME - I would not have participated in Verapamil injection studies either. I would have gladly participated in studies of Pentox, verapamil cream, oral supplements, etc. I am not sure I would qualify, as my disease has never been "stable" as defined by no changes for a long period of time.
The worst thing for them to do would be to include folks with minor changes that would not easily show improvement, and thus wash out the statistical significance of treatment, and thus lead to the drug not getting approved. That is a real possibility of a poorly designed trial. A famous vitamin C study that showed "no effect" used a daily dose of 250 mg - it is still widely cited as proof that supplemental C is of "no value", while better but smaller studies continue to show the opposite.
Let's help this company do a good study and volunteer when we can, and help move it forward. If we do not qualify because we are too severely or too mildly affected, well, lets stand by and hope for a good outcome and future availability of a drug that might help all of us.
Tim
I think that you need to focus on your mental health. You seem to have already learned that altering your behavior has helped you out socially (ie gotten you out of Juvy), but if you can find more social and mental health support, you will be helping yourself greatly. Finding a source of therapy to help you cope with not only a urologic problem but also with enormous family stress would be to the good. Many young people with terrible situations have moved ahead and out of them and so can you.
For now, I would focus on a few healthy things. First, getting a healthy erection daily is probably good for you. Doing this without porn, or sex involved is better, as you do not need to inject any other obsessive thinking into the picture, and what we all want is a healthy loving sex life some day anyway, right? So if your hope and desire is to one day be in a loving sexual relationship with the girl of your dreams, don't become the guy she would never like (a porn obsessed wanker!). Many of us have added a daily erection to our life using the VED, but you might be able to get hard - ALONE - without one. Please postpone getting sexual with a girl for just a little while.
If you can find a way to get regular erections, then you will get a much better idea of what is going on with your penis. A bend to the left, but sometimes to the right is NOT typical for Peyronie's Disease. It is typical for erectile dysfunction, and the most common reason for that at your age is anxiety - which it seems that you have a lot of. So by removing performance anxiety from the picture by chosing not to perform (just for a while!!) should help you get a much better idea of what you penis does when it gets hard.
If it turns out that you have a real bend to the left and down that is new and not just something that appears on the way to a normal straight erection (sometimes the two sides of a penis get hard at different rates leading to temporary bending), then you can start to treat it. You are in LA and you should be able to be seen by members of the UCLA department of urology. You might have to finagle free care - but it might well be that a member of that department can see you. Perhaps the visit to the USC urologist is all that you need. What you have not said is what the urologist recommended for you.
I recommend getting a VED. Also, talk to your Dad if you have not yet done so and tell him what is happening. He can help you purchase a VED, and if too expensive, he can help you make a cheap one using the techniques discussed here by Angus on the Child Boards. I bet that with a VED and time, you may regain a lot of length and straightness.
I commend you on stopping smoking - that is a good one for you and not something a person struggling so much financially should be spending money on anyway. Now develop some healthy habits for your sexuality and masturbate gently, not furiously or repeatedly. With time and more confidence, the sex with girls part will happen just fine.
Tim
Guys, we are really blessed on this forum to have health care professionals like Tim and Ted posting here. I hope that all of you who are concerned about the Xiaflex trials will read their posts carefully. These are the people who have the expertise to know what they are talking about. I think you can take their insights to the bank in terms of trust. On the other hand, I can certainly understand why travel expense will preclude participation for many. But I really DO believe that Xiaflex will likely form an important function in the emerging Peyronie's toolkit and the more guys who take part in the trial the better off we will ALL be in the long run. - George
Welcome despise! First of all, I agree completely with Tim's post. I hope you have already read it carefully and that you will follow up on it. I would also recommend that you simply try to relax and take time to read over the threads on this forum. I would recommend that you begin with the "child boards (https://www.peyroniesforum.net/index.php/board,18.0.html)". These are a compilation of the best posts from the regular forum with the new reader in mind. They will give you an opportunity to learn more about Peyronies. And knowledge is power! I am confident that with all the information available on this site, you will be able to get this condition under control and eventually beat it! So hang in there, there are a lot of people here pulling for you and wishing you the best. Also, another good place to go when you feel like you need help is the "Coping with Peyronies" (https://www.peyroniesforum.net/index.php/topic,30.0.html) thread on the main board. Here you will always find other guys available to encourage you and point you in the right direction when it comes to dealing with Peyronies. But it is really important that you first visit the child boards, that way you will be up to speed on the basic stuff and ready to get real time help on the more complicated issues. I wish you the best young man, you have a great future ahead of you, so don't let this thing drag you down. - George
Hey Despise,
I am young like you. I'm 22, i first noticed this at age 20. Yes, it sucks that you have gotten this so young. If you had to get it at all, it would be ideal that it would happen in your 40's and 50's after the days of your youth were behind you. But I will say that you still have a hope, and a situation that puts you in a better spot than say, me. In 2-3 years this Xiaflex may likely be available to all sufferers of Peyronie's disease, and at such time you'll only be 19 or 20. Make no mistake about it, Xiaflex is a real, concrete hope with a lot of money and medical studies being pumped into it. I think that even if you have long term, serious peyronie's you still have hope of living your 20's in sexual normalcy given the potential of medical advancements to be made available within the next few years.
For now however, I don't think anyone needs to tell you that you need to be more careful in the future and lay off of more aggressive and abrasive forms of masturbation. I think this caused my problems as well, and I too humped the floor as a child (as funny as that sounds). There are many things you will find frustrating and ironic about your condition. One is that it may make you very stressed out and depressed, yet if you take most anti-depressants it will likely be bad for your sexual condition. I have recently started taking 25 mg of Trazodone to help me sleep at night after reading on this forum that it is one of the few of those types of drugs that can actually help erections rather than impairing them. It has helped me sleep a lot better, which probably makes the next day easier to cope with.
Hi Everyone. I am new to the forum but have read most of it over the last few months. I'm 39 from the UK, had this devastating disease for 4 years, currently on Pentox for last 4 weeks (late I know but giving it a go).
I have a couple of questions on treatments that I hope fit under this category and would appreciate your advices on.
1) Xialflex being the enzyme Colleganese is currently being injected. EMDA has been shown to be able to transport Verapamil into the Tunica so could that happen with Colleganese? Whilst I would take the needles if it would help I was just wondering could there be another option as a 1st line treatment.
2) If Xiaflex was succesful, one way or another we are looking at 2 years. If you underwent traction in the meantime and that succeeded in stretching the plaque so it was thinner would that negatively impact a possible future Xiaflex injection in that the plaque was not as concentrated? Ideally disolving as much plaque as possible and remodelling into healthy tissue is the preferred outcome so would not want to jeopardise the current situation if 2 years out a viable treatment was available.
Welcome to the forum UK.
I am probably drawing a momentary blank but I am not familiar with EMDA or studies conclusively establishing that it, DMSO or anything else transports Verapamil into the tunica. Whether DMSO (which I am familiar with) transports anything is based primarily on the molecular weight of the substance involved. I do not have the weight at my finger tips nor do I know the molecular weight of Colleganese. Beyound molecular weight I am sure there could be many other considerations from the absence of needle perforation of the plaque to interaction of the substance with DMSO and even control over depth of transport.
I personally doubt that traction could have a negative impact on future Colleganese use but in reality, only a clinical trial could establish this and I doubt that we are likely to ever see that. I would certainly suspect Colleganese and traction used together would give better results than either used alone but these are just my thoughts.
Clinical Trial update:
I'll be in Houston on Monday for the initial screening. As soon as I know if I'm in the study or not, I'll let everyone know.
UK,
I doubt VED use would affect the results for later use of Xiaflex. If I were doing a study, I would like to treat pristine and previosuly untreated Peyronie's, to really see what my thing could do. The study is designed to exclude those using other methods of cure simultaneously (ie VED) and demands that you not have done any other such therapy for a period of time before entry into study (can't recall if it was 3 or 6 months).
Tim
Tim:
It's 2 weeks.
Quote
Used any mechanical type device for correction of Peyronie's disease within the 2-week period before screening or plans to use any these devices at any time during the study
Used a mechanical device to induce a passive erection within the 2-week period before screening or plans to use any of these devices at any time during the study
All,
I had my first injection today, as part of the Xiaflex study. My doctor mentioned that he still had slots available for five more participants, that there was a 10-day window remaining to get into this study, and asked if I knew any men who'd be interested in participating. I mentioned this forum and he OK'ed my posting this info.
His name is Dr. Ridwan Shabsigh, and he's the head of the Urology department at Maimonides Medical Center in Brooklyn, NY. If anyone is interested in participating, you can contact his study coordinator, Kimberly. Her number is 718 283-7634.
A few things worth noting, that were discussed previously here: the consent form says you have a 3:1 chance of receiving the study drug, versus the placebo. I reported here previously that I'd had verbal assurances from the Dr. and his study coordinator, that the drug would be made available at the end of the study. But when I raised the point today, in the context of mentioning it on this forum, he backed off and said he couldn't assure that. He said he hoped that he would be able to make the drug available at the end of the study, but he wouldn't guarantee it.
My personal take is that by participating in the study, I've got a 3:1 chance of getting the actual treatment, and if I'm in the placebo group, there's still a chance I'll get the treatment at the end of the study. If I don't participate in the study, I've got zero chance of getting the actual treatment. The calculus would of course be different if you have to incur the expense of flying in, etc - the study requires numerous visits.
Last, I'll just say that notwithstanding the Dr.'s waffling about the placebo group getting the study drug, overall I completely trust his skill as a doctor, in particular his experience with Peyronie's. His research coordinator is also very professional and easy to work with.
So if there are any guys within reach of the NY area, who've been on the fence about getting involved in this study, here's a chance to do something.
G.
G.,
Thanks for the great post. This is one of the many benefits the PDS forum was setup to facilitate.
G,
Thanks for the post. Can you please describe how the injection went? Was it painful? Was it a single injection? Did you develop a hematoma (bruising) at the injection site? Are you able to see any immediate results? If not, when should you expect to see them if you received Xiaflex? Thanks!
G.
are you in the modelling or non-modelling group?
Hi Believer,
The injection was a single injection (directed at the location of maximum curvature/thickness of plaque), and yes, it was fairly painful. Not eyes tearing, can't stand it painful, but definitely not fun! Fortunately, it was over in a matter of seconds. The doctor did offer to administer an anesthetic first, but pointed out that that would be an injection too, so I figured, let's just get it over with. Not sure if I'll ask for anesthetic when I go back for second shot on Monday; depends on how sore it is then, I guess. If it's any help, this doctor really knows what he's doing.
I definitely have some soreness there, but not severe. There's a small lump on the shaft of the penis, under the skin, where the injection was. I have no idea yet whether got the real thing or not, I figure it would be sore either way, after getting an injection there. Also, this happened earlier today, so I haven't had any opportunity to see how this may have affected my erection - probably it would be way too soon to tell, anyway. I'll post back if I see anything significant after I get the second injection.
A couple of other things that may be worth mentioning, if you're considering participating in the study:
- It says in the consent form that they expect you can resume normal sexual activity two weeks after each treatment (i.e. second injection in a series). I'm going to ask the doctor on Monday whether that precludes all sexual activity of any kind, because going two weeks without any relief in that department is kinda hard!
- You also have to agree that if you're sexually active during the duration of the study, that you have to use contraception. I suspect this has more to do with avoiding liability on their part than with any real risk, but regardless, you have to agree to that to participate.
jon, just saw your reply when I was about to post this. I'm in the modeling group. This means I have to go in for a third time (this coming Wednesday, after injections Saturday and Monday). They said I would be shown a video, and then the doctor would do this modeling on me (which I gather is some kind of stretching) and then show me how to do it myself. I'll then be expected to follow up with doing this at home. Actually, I'm glad to be in the modeling group - I figure if it increases my chances of improvement, it's worth trying.
hth,
G.
G.
I'm going in for my initial screening on Monday, how did that go for you?
Like you, if I make it into the study, I'm hoping to 1) get the real thing and 2) be in the modelling group, but I'll be happy to just get the real thing, since I'm driving 270 miles each way to participate.
jon,
Looks like our posts crossed. The screening was not a big deal, mainly taking blood, urine etc. I guess the biggest deal is that he gives you a (non-painful) injection to induce an erection, and then he examines you with an ultra-sound device. I had had this same procedure 3 years ago when I first consulted this doctor for my Peyronie's (same doctor who is running the study I'm in), so I knew what to expect, like I said, not a big deal - in fact, the experience makes for a good war story!
Good luck, hope you get in.
G.
As always, I am curious to hear from those of you who have by now received more than one treatment with (possibly) Xiaflex...as long as it does not jeopardize your ongoing participation in the trial to do so!
Also, pirfenidone...seems like now would be the time for all of us to collectively alert the company to the plight of us here and everywhere with Peyronies Disease and see if they might not further investigate whether we could be yet another population of patients who could benefit from the drug. It seems that it will likely be available sooner than Xiaflex even, and although it will most likely not reverse what is already done it could be the preventive drug we have been hoping for.
Thanks everyone for all of your input. I'm still not good at navigating on this site, so please bear with me. Recently, I applied for pre-authorization for surgery. It was denied. I filed an appeal and asked the physician to please file jointly. Looking forward, if the appeal fails, I suppose I will attempt to negociate "price", and if that fails, I suppose I will be resigned to a "wait and see" approach, hoping Xiaflex is everything many of us hope it will be. In the meantime, I am very, very interested in hearing from many of you that have been in the Xiaflex study, especially those that have received more than one injection. Hopefully,.. you will be able to report positive results. Thanking all of you in advance for keeping the "lines of communication" open and flowing. John.
I get to go back on January 9th for the doppler/utrasound and bloodwork. But so far so good for meeting the inclusion criteria and not hitting anything on the exclusion list. So nothing really to report yet aside from my plaque measurement via micrometer: 12mm x 56.5mm
Hi, I just got back from my visit to my UK urologist who is supposedly the Peyronie's expert in the UK. I asked him what he knew about Xiaflex and how he thought colleganese worked. He said he had asked to be included in the trials but had not heard anything back from Auxilium. What he told me was pretty negative and not how I had understood it to work. This is exactly what he said - the collagenese would dissolve the fibrosis, the penis would be stretched and the fibrosis would be replaced with further scar tissue but in the stretched form. He said in his opinion it was highly unlikely that healthy tissue would form or scar tissue could be remodelled into healthy tissue.
I was basing my understanding on the information in this link, so obviously his comments did not fill me with hope.
http://books.google.co.uk/books?id=fLlNmRPzaEEC&pg=PA83&lpg=PA83&dq=collagenase+peyronie's+60%25&source=web&ots=bFDjs8eZXs&sig=VY-ih9k_PMQPqk6dB5NnNqz1VZk&hl=en&sa=X&oi=book_result&resnum=4&ct=result
Also the previous Phase I/II Auxilium trials were not with modeling which I believe he was referring to.
Is he misinformed or not as much an expert as his reputation is made out to be? One of the posters that had underwent the injections mentioned the dent had been reduced (after days), surely that is a sign of elasticity returning and not new fibrosis forming. Wouldn't the new fibrosis take months to form, so what is replacing the dissolved scar tissue? Positive comments appreciated as I am feeling really negative right now and this was really my only true hope of reversing some of the damage.
UK, my own (layman's) interpretation of what he said would be more positive.
Xiaflex can't stop the underlying process that's causing the fibrosis - whatever that actually is. It can dissolve existing collagen deposits, which would restore some elasticity, at least temporarily. Stretching the tissue would be a way to retain the gains in straightness and length even if elasticity is lost again over time. The progression of Peyronies Disease is unpredictable, so I think it's quite possible that the fibrosis doesn't recurr, at least for a long time.
My understanding is that the treatment should be repeatable, if necessary, as time goes by.
The fact is no one really knows if stretching or modeling will help to lessen the curvature. Auxilium's modeling may or may not be the correct approach. We will have to wait for results of the trial to find out.
Speaking to the topic of modeling - I just had my first session of that today, as part of the Xiaflex trial, so will relate how it was explained to me: what I was told was that it was hoped that the injected drug would break down and/or weaken the fibrous tissue. The rationale for the stretching was that, with the fibrous tissue weakened or broken down by the drug, that the stretching would break down the fibrous tissue even further. There was some mention that the results of the earlier trials supported this theory (i.e. apparently some men in the earlier trials did this stretching too), but they didn't go into details. They also didn't go into detail as to what kind of tissue would replace that, and I didn't think to ask. The rationale given seemed logical to me, and the stretching technique I was shown seems well-designed, so I'll stick with the program and see what happens.
Following up on my post of a few days ago, I had my second injection on Monday, and this didn't go too well - basically I ended up with a hematoma a couple of hours later and was in a fair bit of pain for a couple of days. Fortunately it's getting better. Not knowing anything about the topic, when I initially saw this happening, I figured at least this must mean I got the drug rather than the placebo. But what I've learned in the past couple of days, and confirmed by the doctor, is that the hematoma had nothing to do with the drug or placebo - it was just that a blood vessel got nicked in the course of the injection. It was suggested that when I get the next set of injections, I should be more careful about applying firm pressure for several minutes afterward, which I definitely did not do this time. Apparently the second injection in a series, is often tougher due to the after-affects of the first injection still being present. They didn't seem at all surprised this had happened.
With all this going on, the opportunity to examine my curve didn't arise until this morning, and there's no change in the curve at all (at least it's not worse!). So at the moment I'm thinking I may be in the placebo group, and am a little bummed about that, but I'm definitely committed to stick with the program and see what happens.
G.
Quote from: G. on December 17, 2008, 06:30:58 PM
basically I ended up with a hematoma a couple of hours later and was in a fair bit of pain for a couple of days. ...the hematoma had nothing to do with the drug or placebo - it was just that a blood vessel got nicked in the course of the injection. It was suggested that when I get the next set of injections, I should be more careful about applying firm pressure for several minutes afterward, which I definitely did not do this time.
G,
Do not underestimate the importance of applying this pressure. The hematoma can form under the skin, in the cavernosa, or anywhere else in the penis structure. From what I have read, whole blood in any tissue can trigger formation of scar tissue, or adhesions or (plaque) and it is an issue in surgery in general. I strongly suggest you make sure you apply that pressure to prevent bleeding into the tissue.
I guess I misunderstood what UK was saying. I was thinking of long-term stretching, after the Xiaflex treatment, as a maintenance program. Apparently what they're doing in the trial is similar to what they do with Dupuytren's - inject, wait a while and then stretch right on the spot. It makes sense either way. After Dupuytren's surgery you wear a night splint for months so you don't lose what you've gained.
Hawk,
Thanks for reply - I'll definitely be on top of this next time I get injected. Reconstructing events, the doctor told me to apply firm pressure for a few minutes, then a minute later told me I could get up and get dressed, so I obeyed. He's a great doctor, but with the caseload of this study on top of his regular practice, he does seem rushed these days.
On the day I got the first injection, I had asked him whether there was any concern that anyone in the placebo group might actually be harmed, due to bruising or some other reaction to the injection. He said no one in the placebo groups in any of the earlier studies, had any adverse affect on their condition. Hopefully, I won't be an exception. Fortunately, I'm a quick healer so I'm optimistic this won't have any lasting effect.
G.
PS: Want to clarify something I posted a few days ago, about resuming normal sexual activity 2 weeks after the second injection. I asked the doctor about this; he said I could do whatever I was comfortable with, the language about 2 weeks was just to say that at the max, you'd be able to resume sexual activity by that timeframe.
I guess for me I'd be concerned over getting the placebo, which one does not know if they are getting or not. I say this because just getting injections with no medicine can't be good. As we saw in our survey most people who got verapamil injections saw no improvement and some got worse. I just can't see how stabbing a needle into the penis will cure anything and only create more scar tissue. I'd be very reluctant to join any trial study because of this. Nonetheless, someones got to to do it to get this ball rolling. It will be very interesting to see the final results of this study.
Comeback
Something is happening with Auxilium stock last few days, Tuesday up 10%, Wednesday up 6% and today opened up 18%.
Could there be some news on the horizon?
That's it, Pfizer has bought the rights to Xiaflex, could this be a breakthrough for all of us or a hindrance.
Wow - that is a big deal. Link to article: http://money.cnn.com/news/newsfeeds/articles/marketwire/0461453.htm (http://money.cnn.com/news/newsfeeds/articles/marketwire/0461453.htm)
This can only be good news. For starters, it validates that Auxilium has got a viable product with real potential - Pfizer is not going to make that kind of investment unless they see the science as sound, and see commercial potential. It also means that Auxilium is not going to run out of money and/or go out of business before the product gets to market. And having Pfizer as a strategic partner should definitely help in getting the product through the approval process.
In the article, both the Auxilium and the Pfizer people talk about the potential for Xiaflex in treating Peyronie's as well as Depuytren's - so this is also noteworthy in getting Peyronie's attention as a 'mainstream' disease:
"Today, Pfizer and Auxilium have forged a compelling partnership and together we believe we have the opportunity to offer the first, effective non-surgical treatment for two diseases," said Armando Anido, Chief Executive Officer and President of Auxilium. "With the strength of Pfizer's commercialization and development organization, this relationship greatly enhances our ability to effectively introduce this potentially groundbreaking technology for the treatment of Dupuytren's contracture and Peyronie's disease in Europe."
G.
Pfizer spells $$$$$$$$$ for Auxilium. This means Phizer thinks Xiaflex is ready for the fast track for both Dupuytren's contracture and Peyronie's disease. And nobody knows better than the big drug pushers like Pfizer how to get a potentially money making product on the market in no time. Money moves mountains and Pfizer has what it takes. Pfizer also knows very well that these are two diseases with simply no proven effective treatment at this point which means success on the part of Xiaflex has the potential to enrich Pfizer in return. - George
G:
Am I reading the last sentences in the excerpt of the article where is says in Europe right or not? ?What about the good old USA?
Is there any reference to its being available in the U.S. anywhre in the article??
Old Man
Old Man, I don't really think that makes a whole lot of difference. Just the fact that Pfizer is along for the ride on this will add money to Auxilliam's coffers and be influential with the powers that be. And I think it will guarantee its introduction to the US market at a time when the success of this product was not guaranteed previously due to financial vulnerability on the part of Auxilliam. - George
Old Man
Good old USA? I thought it was good old Europe... ;-) Sorry, just kidding!
Hey folks:
Pfizer jumping in is a great thing. With regards to Europe, often times, approval for a drug happens quicker in Europe then it does in the U.S. Many companies start marketing and sales in Europe to maximize profit. I'll fly to France for this stuff! This is also about distribution. A company like Pfizer has a massive capacity for distribution and they are also a U.S. company. There is probably a connection just in the ability to do business because they are both U.S. companies. Auxillium does the research and manufacturing. Pfizer does the marketing and distribution. I don't know if Pfizer has a urological field force in the U.S.
As for the doctor that said "it was highly unlikely that healthy tissue would form or scar tissue could be remodelled into healthy tissue" is odd. The tunica albuginea is two sheaths of tissue and the scar forms between them. At the site of the injury, it actually isn't supposed to deteriorate the scar. It is supposed to break down the excessive formation of the tissue.
The doctor's statement doesn't seem to comport with the literature. Hmmmmmmmmmmmmmmmmmmmm.... and older doctor with habits giving out half-assed information to a patient that is more knowledgable then them on a particular treatment? That never happens!
Keep the faith! Xiaflex is coming.
will it make it downunder????
Quote from: Ted Williams on December 18, 2008, 08:58:10 PMAs for the doctor that said "it was highly unlikely that healthy tissue would form or scar tissue could be remodelled into healthy tissue" is odd. The tunica albuginea is two sheaths of tissue and the scar forms between them. At the site of the injury, it actually isn't supposed to deteriorate the scar. It is supposed to break down the excessive formation of the tissue.
The doctor's statement doesn't seem to comport with the literature. Hmmmmmmmmmmmmmmmmmmmm.... and older doctor with habits giving out half-assed information to a patient that is more knowledgable then them on a particular treatment? That never happens!
I could recall a long list of famous assertions by doctors extending all the way back to Pasteur, who as a chemist knew more about what he was doing than most of the medical establishment of his day. Then there were the medical experts who insisted that surgery on the heart would NEVER be possible. AND the crazy docs in Australia who had the audacity to attribute ulcers to a bacterial infection when every doc worth his salt KNEW that ulcers were caused by stress. And for years it has been boilerplate in the medical community that damaged hearts have to be replaced with transplants because a damaged heart CAN'T heal, until a damaged heart was left in with a transplanted heart due to extenuating circumstances and ... lo and behold the damaged heart got well. Now the urologists are turning up their noses at the use of Pentox to treat Peyronies and the general practice docs are resisting the emerging research on Vitamin D in the amount of literally thousands of studies, 99% of which point in only one direction. Its truly amazing how "evidence based" practitioners get bound up in myths. They come to conclusions without any real evidence and then repeat them to each other for so long that they eventually end up believing them to a point of religious conviction and they fight if somebody comes along trying to confuse them with facts. And so it is with the lowly tunica. The realities of physiology be damned, they have an opinion and nobody is going to stop them from expressing it no matter whether it actually makes sense or not. Thanks for all your great posts, they are right on the money. So great to have you contributing to the forum! - George
PS - pdpunk thinks we hate doctors around here. He couldn't be further from the truth. We esteem doctors very highly. But we have to admit that on occasion they are our favorite form of entertainment. Gee ... they must be human! (Just like us.) Highly educated, highly trained, highly skilled, but still quite human. And that is a GOOD thing! But it does have a downside now and then. We accept them with their foibles and we sincerely hope that they will accept us with ours!
Although I believe that the incidence of Peyronie's is greater than recognized, and that many men could benefit from a "cure" (I do not think that Xiaflex shall prove to be a cure - it will help some but not all, I bet), this is small potatoes compared to heart disease and cancer.
Pfizer may well have bought the rights to eliminate competition - it happens. Drug companies sit on drug development if it is not going to be a homerun; Pfizer is more likely to do that than a small company that is only making one or two drugs.
We shall see - I would be more interested in who is making money by the stock options that are flying about than who is going to see the light and start to make Xiaflex available sooner (or not).
Tim
We had such a good roll going here until who should show up? The devil's advocate it seems in the form of our own Dr. Tim! So ... Tim ... now that you are throwing this cup of cold water in our laps, do you actually know of some prescription med for Peyronies made by Pfizer? The only Peyronies med I know of at this point is Potaba which is made by Glenwood. Or perhaps Pfizer has some killer Peyronies product ready to launch? The plot thickens! Tell us more o wise oracle! - George
I have to agree with Tim. It isn't that often that there is that single cure all drug for everyone. I hope I"m wrong. Does anyone know how well Xiaflex works for Deputryn's Disease? Maybe the success rate will be similar.
Les
For the record, as far as THE cure is concerned, I agree with Tim also. I think Xiaflex has the potential to be a great tool, but the cure lies much deeper than just burning off some collagen. You also have to stop the collagen from returning. - George
Guys,
I've followed some of the posts and I hope to have some more feedback in the next month or so once I've had another evaluation and have better idea where I stand. I think I have gotten the real drug but there is no way to know for sure. Regardless of what I got and as hopefull as we all are, everyone should have realistic expectations. Based on what I've heard from my doctor, the assistant and my own experience I think Xiaflex can be helpful in varying degrees to most of us. It breaks up tissue but not necessarily evenly and the same for everyone. Any progress should be looked at as the glass is half full not half empty. I agree with what was said that it is not a cure. Expect progress but not to have your plaque magically and evenly melt away like a pat of warm butter. I think it could be a great advancement and I would definitely seek it out, but I don't expect to be back to the way I was at least in 3 series if at all. I'm just one of many so anyone else please jump here. I don't want anyone to be discouraged but I sense some euphoria and I think everyone should be hopeful and confident but not unrealistic. I am also confident that my doctor and others will use Xiaflex as on off label use for Peyronie's once it is approved for Dupuytren's. It will most likely be approved in Europe first.
Hello Vernon,
Thanks for keeping things realistic. I appreciate your candid evaluation of your own condition and experience with the Xiaflex Trials. I always imagined that Xiaflex would break up the big blocks of fibrotic material, but in the end, it would be our responsibility to follow up with VED, supplements, Pentox and whatever we have discovered to address the condition further.
Please forgive me if I made slights at the doctors on the front-line of our battle. Peyronie's is one of many conditions that these doctors deal with. The deluge of theoretical and experimental treatments for all of the conditions they confront is overwhelming. I don't expect them to know everything. I hope that the recent moves made by Auxillium will enhance the profile of this treatment.
I am hopeful for a powerful, non-surgical tool in our tool box.
Keep us posted.
Ted Williams.
I don't know of any Pfizer drugs. I was thinking of Intermune that stopped studying Pirfenidone when they had Actimmune that seemed to help. A patient filed suit to force them to give pirfenidone under compassionate use, and then extended it to try to force them to study it - even though it was possible it would undermine their treatment (and revenue stream) from using their other drug (Actimmune) for IPF. See, I think Pirfenidone would not have made them as much money, and it looked like they were going to sit on it until the patent for Actimmune ran out to ramp up work on Pirefnidone.
So, no inside information, but for now, the amount of income from Xiaflex to Pfizer would be like the leftover money for the office coffee fund would be for me at the end of the month.
Tim
Is there indication that InterMune is still sitting on this? It is listed on their product pipeline, and has just been approved in Japan.
Jack, They WERE sitting on it. Basically, dying IPF patients and their families made enough of a stink to make them continue development of Pirfenidone. - George
My own somewhat cynical analysis:
When a major corporate player decides it wants in on something, it's hardly ever a good thing for the public. These people are only interested in really-big-money plays, and their timelines are in decades. Any immediate benefits to us, the patients, would be purely a side effect.
Their stated intention seems to be to market Xiaflex in Europe, and leave the US to Auxilium. But I have doubts about that statement; at best, it just describes the initial agreement. Pfizer could simply buy out Auxilium at any time, toss Auxilium's plans into the waste bin and start over with a whole new marketing, distribution and pricing scheme that would take years to implement. And as tim468 points out, one nasty but real possibility is that they simply kill the product
There's no way to know. The combination of our stock market, our intellectual property laws, our madness for litigation - plus corporate and individual greed - can be a toxic mix.
While cynicism about the major drug companies is warranted many times over, in this case I don't see the benefit to Pfizer to acquire Auxilium and then just kill the product. For one thing, there's been reporting that the major drug companies are running out of new prospects in their own pipelines, and many of their big profit-makers are going to go off-patent in the next few years. So they're actively looking for new products, particularly in biotech - see this article, for example: http://money.cnn.com/news/newsfeeds/articles/djf500/200812161237DOWJONESDJONLINE000576_FORTUNE5.htm (http://money.cnn.com/news/newsfeeds/articles/djf500/200812161237DOWJONESDJONLINE000576_FORTUNE5.htm).
For another thing, although the income from Xiaflex would never rise to the blockbuster category, it could prove to be very profitable. I thought I read somewhere that when this was commercially available, it was expected to cost in the neighborhood of $11,000 (did I read that on this board, some time ago?). Anyway, let's say eventually 50,000 men per year were getting this treatment worldwide. If $2000 per patient flowed back to Pfizer, that would be $100 million per year in revenue, just for this one application. Even if the number were lower than that, it would still potentially be very profitable. And unlike the Intermune example cited, there's no evidence that Pfizer has any competing product in their pipeline - so, hard as it is for me not to suspect the motives of a big drug company, it's hard to see why they would kill or delay Xiaflex in this case.
G.
The way I do my business I need correct, up to date, factual information
in order to make decisions. "What if", "Maybe they" does not help. Solid
information is what we need.
I know that inhaled TOBi is worth 300 million a year to Novartis, and they think of that as the "office coffee funds left over at the end of the month" (that is a quote from a man I know working at Genentech). I do not think that most of us can even THINK in terms of how much money big Pharma makes, such that 100 million a year is nothing to them.
The main reason to buy and sell companies is to manipulate stock prices - I note that the stock value went up fast, and before the financial agreement was announced. That sounds like speculation and probable insider trading to me.
Tim
Giants like Pfizer are always interested in picking up companies and products that they think might turn into big money-makers. Sometimes they decide later that the really big bucks aren't there after all, and they lose interest, and the product never happens. Even if they decide to go ahead, they move slowly - Auxilium's success has depended on Xiaflex moving forward; Pfizer's would not.
Dupuytren's Contracture is a very common condition especially among older people, and as far as I know there's no product in development that competes directly with Xiaflex. If Xiaflex can replace a lot of surgery, at a cost that's only somewhat lower, there's probably some serious money. I think it will happen.
I propose starting a new discussion thread here for participants in the Xiaflex trial.
My background: I am 57 y.o., going into the trial with a curvature of about 40 degrees. Sexual intercourse has been hindered, but thankfully still possible. I am recently enrolled and have completed my first round of injections. My doc is a well regarded guy in the field and is the go-to physician in my area for Peyronie's. The injection procedure was no big deal. My penis was completely numbed and I never felt a thing beyond the initial injection of the local anesthetic. Thus far I have experienced a lot of bruising and swelling which I was told to expect. After 3-4 days these symptoms are decreasing. Though not particularly enjoyable at this time for obvious reasons, I have had small erections which have produced a distinct tugging sensation in my penis. I hope that is indicative of the collagen breaking up. Based on these observations, I am pretty certain that I am not getting placebo so I am very happy about that. All in all, it has been tolerable so far.
Other participants-please post your experiences. Thanks and good luck to all.
rbwoodward
What is the course of injections, you get one weekly, every two weeks etc? What region of the usa are you located in? I like the idea of starting a thread on this to compare experiences, I'm unsure of exactly how many members in our forum are in the clinical trials. Have you tried any other treatments before this, and if so what results did you see or not see?
Comebackid
There is a concern that should there be a seperate Xiaflex thread, everyone will post in there and this thread will die out, or there will be cross posting etc. I can see how that could be a problem. There does appear to be great interest in the Xiaflex trials though, so maybe there could be a Xiaflex thread specific to those currently receiving treatment to detail their progress (or lack of) and ongoing experience. In this thread (development drugs and treatments) we could then ask followup questions concerning the Xiaflex thread updates, but the Xiaflex thread itself would be an uninterupted thread consisting of treatment updates and thoughts from only those involved in the clinical trials. This would make it very easy to get a feel for how the trials are going, and also may make it more likely that newcomers and lurkers receiving Xiaflex will post since the thread will relate very specifically to their situation. Just my view.
I understand newguy's concerns about starting a new thread. It does not really matter to me, whatever works for the group is fine.
To comeback kid: The first round of two injections is given over 24-72 hours, I believe. I am not sure when the next round comes, probably in a few weeks. I have not tried any other treatments. There are lots of trial sites around the US. Does anybody know the url for the listing of those sites?
rbwoodward - http://clinicaltrials.gov/ct2/search and then type in Peyronies
rbwoodward:
here's the link:
http://www.clinicaltrials.gov/ct2/show/NCT00755222?term=peyronie&rank=1
The Xiaflex trials have been going for quite a while now - surely surely surely there must be someone out there with some feedback on how its working - hasnt anyone gone back a second time and can report on some improvement - surely this MUST be a priority for ourselves here???? shouldnt we focus on this?
Going on holidays now....
Iceman:
Please reply to my PM. Thanks
I kind of agree with you that we should hear from people who are in the study. On the other hand I don't want us to disrupt the study and have it be deemed non - scientific for some dumb reason. If people on here starting talking about what region they are in and what doctor they have etc... this could influence the study, or someone could accuse the forum of influencing members in the study. I know it is tough to stay patient but hey at least we know the trials are under way!
Comebackid
Iceman,
If the study is a randomized double blinded study, that means that neither the investigators or the subjects know if they are getting placebo or study drug. If for some reason we get a bunch of guys here who ended up with placebo, then we are going to get some bad reports (or vice versa). We just have to wait.
When I have done drug studies, we usually do an interim analysis to be sure that nothing bad is going on, but even then we do not break the code for who is getting the drug. I have been fooled completely by thinking that a guy got drug, when he did not. Another kid had a "probable" adverse event who got placebo. So it goes. So again, we are going to wait, for we have no choice!
Tim
Hey guys,Just a short note to let you know that I am in the Xiaflex study.I will be going in on Jan 14th for my second series of injections.I have posted in the past that I was one of the ones in the study.I really have not posted too much because i am really not sure if i got the drug or not.I am still sore at times and it does lead me to believe that I got the drug but other times I think I might not have.I feel that the plaque got softer but my curve is the same(so it seems)I will be going in on the 5th for measurements then back on the 14 for the 2nd series of injections.I really don't have a lot of positive info to share but don't want to discourage anybody either.I will post after my second series.Thank You,Ticker
Just a short note along the lines of the one just posted by Ticker:
No progress to report so far - the bruising from the second injection (of the first set) went away after four or five days, but there's no difference in my curve. I figure I may have gotten the placebo but not drawing any conclusions. I'll get re-measured and then a second set of injections in mid-January - will post back after that.
G.
Sometimes it is helpful to get an additional perspective on a deal like the Pfizer/Auxillium thing. I just picked up this interaction that demonstrates an investor/outsider perspective:
Quote from: CNBC
Pfizer's 40 Year Run Of Hiking Dividend Ends (http://www.cnbc.com/id/28057594)
Funtleyder says Pfizer's standing pat can be viewed two ways. On the one hand he writes, "The dividend is still above seven percent which makes the company seem almost distressed." But on the other hand Funtleyder says, "Despite the company's (approximately) $27 billion in net cash...they might be penalized for using any cash. The longer the cost of capital stays high, the more cash on a balance sheet becomes a competitive advantage. Should we be in for a prolonged lull in the capital raising cycle, PFE may be able to buy its way out of some of its pipeline deficiency."
Note that Pfizer apparently has a "pipeline deficiency". This means that they are desperate at this point to find new products to continue to generate profits into the future. Much of this desperation is due to their Lipitor patent expiring soon.
Quote from: CNBC
Pfizer's Pipeline Envy (http://www.cnbc.com/id/28299600)
There are so many partnerships like this being struck here and there that normally I wouldn't blog about it. PFE's paying AUXL $75 million up front and if everything goes according to plan another $410 million over time. So what makes this so unusual? Well, it's the drug AUXL is developing. It's a two-in-one for a rare disease that causes fingers to curl toward the palm and--and, no, I'm not making this up and it's not a joke--for penises that curve. The "problem" is called Peyronie's disease and it reportedly affects one to four percent of men. I'd never heard of Peyronie's until I read the press release.
Here we get a perhaps typical reaction from an investor perspective regarding Pfizer's new investment. Does anyone else see the potential for a little education to be going on among the general public regarding Peyronie's?
And this whole discussion IS being followed in the blogosphere, here is one example:
Quote from: Rx Recruiting
How Will Pfizer Spend Their Cash? (http://harrisongroup.blogspot.com/2008/12/how-will-pfizer-spend-their-cash.html)
Mike Huckman of CNBC reported earlier this week here that Pfizer's streak raising dividends ended after 40 years. What does this signify for Pfizer? ... Late this week we got an answer. Pfizer signed a drug development partnership with Auxilium Pharmaceuticals and is paying $75 million up and and up to $410 million over time if additional milestones are met. But as Huckman writes....this is not your "typical" drug partnership ... I don't know about you...but if I still owned Pfizer stock...I think I would rather that they just gave me the dividend.
So here may be a typical reaction from someone who knows nothing about this Peyronie's thing.
But there is more:
Quote from: Rx Recruiting
Update re: Pfizer and Peyronie's Disease (http://harrisongroup.blogspot.com/2008/12/update-re-pfizer-and-peyronies-disease.html)
And in my post, I was somewhat critical of Pfizer's decision. However, a reader was able to provide me with additional information re: Peyronie's Disease. It turns out that that the number of men suffering from Peyronie's Disease is not 1-4%, The percentage of men afflicted by the diesease is 9%. ... Nevertheless this drug will improve the lives and health of a significant percentage of people. And, when it comes down to it, improving the lives and health of people is the real purpose of the Pharmaceutical Industry.
So you see what I mean about this Pfizer acquisition bringing Peyronie's prime time exposure and offering educational opportunities!
Quote from: Rx Recruiting
Additional Information on Peyronie's Disease (http://harrisongroup.blogspot.com/2008/12/additional-information-on-peyronies.html)
I have had the good fortune to have been communicating with Stan Hardin who is the head of The
Association of Peyronie's Disease Advocates. Stan reached out to me after I had written a post that was questioning Pfizer's decision to partner with Auxilium to develop a drug for Peyronie's Disease. ... You can read more about both Peyronie's Disease and Stan's organization at their website here. The site is extremely well done and informative. And best of luck to both Pfizer and Auxilium in their quest for a cure.
We may have our occasional minor differences of opinion with APDA. But if anyone doubts the good work they are doing for us, I offer the above as just one example of the good work they ARE doing. These are just the kinds of interactions that can bring real potential to the Pfizer deal for all of us here. - George
George,
Your right that is the typical reaction to peyronies, most people don't know what the hell it is. Yes lets hope that there is a good education campaign and stockholders believe the "sales pitch," on why this is a good move. If they are seen as desperate and buying into a company that researches "bent dicks," this could be bad if shareholders don't buy their theory that there is money to be made here. If they don't we could see a sell off and a decline in stock price for pfizer.
" And, when it comes down to it, improving the lives and health of people is the real purpose of the Pharmaceutical Industry. "
Yeah if it is financialy worth it and a profit can be made.... sounds like this blogger wants to sound politically correct now, if it didnt make a profit he wouldnt hold the stock....
I must say before I got peyronies I never heard of a bent dick or even thought about it. I think more people have peyronies or some form of bend in their penis than we think, one look at pornography and you will notice this...
Pfizer (http://en.wikipedia.org/wiki/Phizer)
George, there is no doubt in my mind that the APDA is working hard for peyronies sufferers. However it is my longstanding view that we'd be better off combined.
Comebackid
I have no doubt that Aux and Pfizer will try to draw in investors and as a result they will surely have to sell the need. That is hard to do without some education and some light being shown on Peyronies Disease. Hopefully it will surpass the Peyronies Disease's only other moment of limelight when a President was allegedly showing his allegedly bent penis as an educational aid (or to an aide, I forget).
How can Aux and/or Pfizer NOT promote this product if it tests out? hopefully it will be like the ads we all see for "ask you doctor about..." products all over TV.
Auxillium has funded some things for the APDA so there is a pretty cozy relationship between Aux. and the doctors sitting on the board at the APDA. I think we can all rest assured, that if this product works, those to benefit financially will use every innovative ad campaign possible to draw Peyronies Disease sufferers out of the closet and into the market. Pharmaceutical reps will as well, surely be educating doctors on the fallacies of Peyronies Disease and the ineffectiveness of other treatments.
All of this is a plus EVEN on the off chance the actual product later failed the test of time.
Hopefully,... Xiaflex will come close to hitting the marks. I think we all have that wish on this years Christmas list. Regarding education, that is the duotask of the marketeers. To both education, create the need and demand for the product. My mother, a brilliant business "lady" use to say: "If we communicate, we may succeed, it we don't, it's assured we won't. While I think many of us have become appalled, embarassed and totally turned off to many of the ads out there (i.e. Viagra, bladder control, male enhancement, and female self pleasuring devices),.. I feel comfortable in believing the marketing giants can approach, create and educate the public and medical professionals alike, of the features and benefits of the product we all hope Xiaflex will prove to be. Yes,.. please put all of this under the tree for me this year, Merry Christmas!
If any product does go to market, we know that it is a given that there will be a marketing campaign to have everyone with possible Peyronies Disease symptoms ask their doctor about "ABC" or whatever. A possible ad would go something like:
"Did you know that Peyronies Disease can cause penile deformity, loss of length and girth, ED, painful erection and lumps or nodules called plaque on the penis. If left untreated Peyronies Disease often leads to deformity significant enough to prevent intercourse. Did you also know that some studies suggest that as many as one out of ten may be affected. Early intervention is critical! Ask your doctor about Peyronies Disease if you have symptoms such as painful erection, onset of deformity, nodules, or loss of size. Xiaflex is the only clinically proven treatment and it can stop and often reverse these symptoms."
OK, I'm no ad man but you get the point.
With the value men place on their organ, it will start an avalanche of weekly penis measuring. It will also likely result is some hypochondria and obsession. It may not be far fetched to say that it may well even spin off VED or traction ads trying to ride the wave.
ED is a widespread common term because Viagra made it so.
Xialeflex is still a long way from hitting the market. There is no general ad campaign, and already it is starting a small ripple of education and discussion.
Hawk,
Not to mention all the literature given out to doctors by pharmacutical reps who will come out in droves to push the product. Did any of you older fellows ever have a routine checkup and have the doctor just bring up viagra or ask you about your sexual health?
Comebackid
I ran across a new study "H-22411: BOTOX® for Peyronie's Disease" at this link:
http://clinicaltrials.gov/ct2/show?term=peyronies&rank=2
"This study is not yet open for participant recruitment. The sponsors are Baylor College of Medicine and Allergan. Approximately 20 to 30 injections of 100 units of BOTOX® given with a 20 gage needle directly into the penile plaque." The location is Houston, TX.
The MedLinePlus link says "Botox injections work by weakening or paralyzing certain muscles or by blocking certain nerves. The effects last about three to four months." Given that, and with my limited medical knowledge, I don't understand how that will affect the plaque which causes the bending. Obviously the people conducting the study believe this will be helpful. Any ideas, opinions, or comments?
One of the side effects of Botox injections in the face is that it may cause temporary drooping eyelids. Does that mean injections in the penis may cause "droopy dicks"? (I just couldn't resist adding that.)
Humorous3
20-30 injections with a 20 gauge needle? Sounds to me like torture and in my humble, not-a-doctor opinion, it would most likely make the plaque worse. Where is the common sense behind this study?
Note to all:
Before embarking on any therapy/treatment involving needles, do your homework. And, realize that with 20 to 30 injections into the shaft that it can and will cause more trauma to the penis. It is not one of the better approaches to any form of therapy for Peyronies Disease IMHO.
The verapamil injections results can be read in that thread/topic elsewhere on this forum. So, cruise through that one and judge for yourself if you would care to get that many injections.
Old Man
Old Man
I agree 100%!!! Do Not Stick A Needle In Your Penis.
I tried trimix injections for about a year with little to no help. The result was corporal fibrosis and more shortening of the penis that was not recoverable.
The VED is the best exercise you can do for you and your penis. Your penis is a prized possession do not abuse it.
Jackp
Guys, we also have to remember that, while it is impossible to get a real study done on something like Pentox because of the huge cost, the manufacturers of stuff like Botox have huge sums of cash to throw around, and if they see any possibility of a new market for their product, there WILL be a study. Personally, I like the posters below, would avoid it like the plague EVEN if they turn up with some short term 'benefit'. Xiaflex at least makes sense, this one does not! Who knows, now that the world is discovering Peyronie's, the next great treatment to get promoted might be acupuncture. ??? - George
Interesting - the other day I was imagining that Botox might be worth studying, and someone else is interested in doing just that!
The contractile nature of the lesions is that of a "myofibrobolast" that is transformed into more of a fibroblast and then the lesion contracts. Thus, in a plaque, it is not just that it fail to stretch out properly, but that it has contracted down (note that scar tissue often contracts also). So, if the lesion's contracting is facilitated by the contraction of smooth muscle that serves as a "ratchet", then preventing that might help.
I also wonder if those who are "grow-ers, not show-ers" would have a larger flaccid "hang" to their penis if the smooth muscle that leads to tightening up were blocked with Botox. Doesn't make much practical difference, but I bet that a lot of egotistical men would love to have a larger flaccid penis. And I bet that if someone showed this to be true (a larger flaccid penis with a simple injection once every three months!) that we would then find a whole new crew of men with Peyronie's Disease.
So, in my mental ramblings, I came to the conclusion that Botox might help, but might hurt. I will wait to see what the data show!
Tim
Quote from: Tim468 on December 26, 2008, 05:31:55 PMSo, if the lesion's contracting is facilitated by the contraction of smooth muscle that serves as a "ratchet", then preventing that might help.
Tim, There are certainly ways to do that short of injecting something like Botox and creating more tissue trauma in the process. There are drugs that achieve the same end in terms of relaxing smooth muscle. But you know as well as I do that the root of the problem biologically is altered tissue in the tunica albuginea and NO AMOUNT of smooth muscle relaxation is going to fix that. AND injections will most certainly run the risk of exacerbating it. Certainly, I wish for the best with this study, as with any study, but it really doesn't look very promising to me and I certainly would not be trying to get at the head of the line as a candidate. If I was really wanting to pursue this strategy (which in fact, I have already pursued to some degree) I would be taking Forskolin regularly since it is a fairly potent smooth muscle relaxant. But when I have used it in the past over a long time period, it produced no real significant benefit. So I just really doubt this whole approach and I really abhor the concept of injections to treat Peyronie's, the exception being something like Xiaflex that actually addresses the inflammation factor directly and would thus seem to have a *potentially* built in way to mitigate the damages it inflicts. Botox on the other hand would seem to hold the potential of itself being an inflammatory agent. No thank you! - George
Don't know if this has been posted before or if this is the right section, but seeing as peyronie's is a fibrotic condition I found this to be very interesting. If they can do this to stop cirrhosis and scarring in the liver perhaps they could do the same to the scarring associated with peyronie's.
December 27, 2007
Liver Fibrosis Stoppable In Mice
Lots of liver diseases kill by causing accumulation of scar tissue. Well, at least in mice the scarring process can be stopped and partially reversed with an inhibitor peptide.
University of California, San Diego researchers have proven in animal studies that fibrosis in the liver can be not only stopped, but reversed. Their discovery, to be published in PLoS Online on December 26, opens the door to treating and curing conditions that lead to excessive tissue scarring such as viral hepatitis, fatty liver disease, cirrhosis, pulmonary fibrosis, scleroderma and burns.
Six years ago, the UC San Diego School of Medicine research team discovered the cause of the excess fibrous tissue growth that leads to liver fibrosis and cirrhosis, and developed a way to block excess scar tissue in mice. At that time, the best hope seemed to be future development of a therapy that would prevent or stop damage in patients suffering from the excessive scarring related to liver or lung disease or severe burns.
In their current study, Martina Buck, Ph.D., assistant professor of medicine at UCSD and the Veterans Affairs San Diego Healthcare System, and Mario Chojkier, M.D., UCSD professor of medicine and liver specialist at the VA, show that by blocking a protein linked to overproduction of scar tissue, they can not only stop the progression of fibrosis in mice, but reverse some of the cell damage that already occurred.
We have been watching bioscience and biotechnological advances for many years. Isn't it about time this progress starts to translate into a whole bunch of disease cures? It is all well and good to watch the progress and marvel at the cleverness of the researchers who find ways to tease out the secrets of biological systems. But getting down to some curing treatments would be great. You might want to see cancer or heart disease cured first. But I'd be happy to see an end to death by liver cirrhosis as a starter.
Inhibition of a protein that actives growth of a type of cell involved in collagen production did the trick.
In response to liver injury – for example, cirrhosis caused by alcohol – hepatic stellate cell (HSC) activated by oxidative stress results in large amounts of collagen. Collagen is necessary to heal wounds, but excessive collagen causes scars in tissues. In this paper, the researchers showed that activation of a protein called RSK results in HSC activation and is critical for the progression of liver fibrosis. They theorized that the RSK pathway would be a potential therapeutic target, and developed an RSK inhibitory peptide to block activation of RSK.
The scientists used mice with severe liver fibrosis – similar to the condition in humans with cirrhosis of the liver – that was induced by chronic treatment with a liver toxin known to cause liver damage. The animals, which continued on the liver toxin, were given the RSK-inhibitory peptide. The peptide inhibited RSK activation, which stopped the HSC from proliferating. The peptide also directly activated the caspase or "executioner" protein, which killed the cells producing liver cirrhosis but not the normal cells.
"All control mice had severe liver fibrosis, while all mice that received the RSK-inhibitory peptide had minimal or no liver fibrosis," said Buck.
Researchers probably had to spend many years teasing out the connection between the RSK protein, hepatic stellate cells, collagen production and scar tissue accumulation. But now they have something really powerful to show for it. Hurray.
But how many years will it take for a human treatment to make it to market?
By Randall Parker at 2007 December 27 09:09 PM Biotech Therapies | TrackBack
http://www.futurepundit.com/archives/004886.html
I recently overheard (just before the holidays) that Dr. Levine's office at Rush University Medical Center in Chicago is still looking for study subjects for the Xiaflex Phase 2b study for Auxilium Pharmaceuticals.
Check out the NIH Clinical Trials website for details on the study. (search on peyronies if the link I tried to insert does not work - look for study referring to AA4500)
http://clinicaltrials.gov/ct2/show/NCT00755222?cond=%22Peyronie+disease%22&rank=1
btw, I don't believe this whole issue about placebo subjects not being able to get Xiaflex in the future is true, in fact I "thought" that placebo subjects might well be asked to participate in Phase III studies & there was some suggestion, assuming the drug is released for Peyronies, it would be offered to placebo subjects, possibly even at no cost
In every Phase 2 or 3 study I have ever done on a drug, drug was offered to those who got placebo when the study was nearing completion. There is either an "open label" phase, where everyone gets drug, or there is a cross over design, where those getting drug are moved to placebo and those getting placebo are moved to drug (this effectively eliminates potential bias selection, and increases the N that helps give a study power).
Tim
I wanted to let everyone know that I will be participating in the Xiaflex trial. They told me the deadline was the end of December, so all I did was sign the consent so far. I have a penile doppler scheduled for this week. I'll keep everyone informed. I just pray that I won't get the placebo.
Joe,
I to would be concerned about the placebo. If you look at our old poll on verapamil injections you will see very little people got better, and quite a few got worse. I have to think that just sticking a needle into the penis will make it worse. There was a technique going on in europe for awhile, leriche or lariche, I forget the name that was supposed to be so effective where the doctor would take a needle and just stab it into the penis. Funny how we havent heard anything about this lately? Personally I think the placebo should be tossed out, you can still determine the effectiveness without it. Considering we are dealing with a very important body organ, there is no reason to play games with placebos that involve sticking a needle in it. This is not a placebo sugar pill, its more than that and could cause damage. Personally I wouldn't sign up myself for any trials until I saw a study showing the drug was effective. With that being said someone has to go through the trials and I wish you the best luck my friend.
Comebackid
ComeBacKid
Can't show a drug is effective until it has been studied. Can't study it without a placebo. It's that simple.
Peyronie's Disease is tough, and we all need to be tough to deal with it. That includes taking risks.
Tim
I understand that inclusion of a placebo in the trials may be required, but in a technical sense I don't see the point. The effect of this treatment is, or should be, objectively measurable following an induced erection. There have already been far too many useless studies of Peyronie's "treatments" where success was determined by the results of a questionaire, i.e. "patient satisfaction". The use of a placebo implies that the evaluation of the results will be weak and subjective. In my opinion the question is not whether the patient's sexual activity or satisfaction improves, it's whether a mechanical/hydraulic problem has been alleviated.
As always - just my opinion.
I do agree with J concerning the low value of patient satisfaction surveys. I am in the Xiaflex study and in addition to surveys ( a waste of time in my opinion), the dr does inject me with a chemical to produce an erection and then measures to determine the degree of curvature. Even with this "objective" measure there can be some degree of variation depending on the amount of chemical injected and the patient's reaction that day.
Both before and after the first set of injections, there curvature has remained exactly the same. No change, at least it did not get any worse.
Regarding the issue of placebo use. I understand the value of using a placebo in trials, but I also think its value is significantly over rated. After all, we are not evaluating relief from headache pain here. I think if one believes that the placebo effect can straighten penises one would have to buy into a whole new dimension in terms of the power of the mind. This would be like going beyond Uri Geller for crying out loud. Unless they are looking for more subjective benefits. In that case why use something as invasive as Xiaflex when we have Pentox? Its sort of like testing cancer surgery by using a placebo candidate and checking them with imaging afterward to make sure that the tumor is not gone as opposed to the one who got the real surgery. The hoped for results are so obvious and physical, I guess I just don't get it. - George
yes, i agree with you George, but I suspect that a placebo is required by the FDA or some similar government organization. As we all know, gov't rules and regulations often make no sense.
I understand why the placebo is needed, for example say the way in which the study doctors injected the drug they were coming close to the lariche technique mentioned. You might see improvement because of that and not necessarily the drug (although that is a stretch in this case there could be similar mechanisms going on). I will ask the Dr this week to clarify if the real drug will be available at the end of the trial for those who've received the placebo.
Also I forgot to mention that the paperwork said there would be 4 groups: drug, placebo, drug with modeling, placebo with modeling. I'm guessing modeling is synonymous with tugging or stretching. They said there was a 3:1 chance of receiving the drug vs placebo.
modeling is some stretching and mostly bending. You may want to ask your dr if you can see the DVD by Dr. Jordan. It is for the Dr and tells him how to explain and then demonstrate the modeling for patients. There is no good reason for not letting you see the DVD and it goes into some detail about the modeling.
I suppose the placebo could be a sort of reverse logic. If bad effects result from the treatment, and they also result from the placebo, then they're just caused by the injections and not Xiaflex.
My favorite placebo story is from Pitt. To train surgeons in technique, they practiced on dogs, and did some reaserch for good measure. Thus, lungs were taken fro mone dog and transplanted into another. In fact, lungs were taken a "moved" in a domino-like series of surgeries were all the dogs served as donors and as recipients. They then got state of the art care in recovery and were started on study drug for immunosuppression.
The placebo group got "sham surgery" (something we do not do with people!!). They were open and shut (BTW, I think this is where the term "it was an open and shut case" comes from - meaning you open up a person and shut them up because there is nothing to do surgically) and so everything was done to the placebo group as with the other dogs, except they did not have lungs removed and replaced.
Interestingly, the sham operation group developed an asthma like condition. If the surgeons (aho also learned technique) had not done the "pointless" sham surgery, we would have thought that the drug caused the asthma like condition.
The point of a placebo is that it gives you a reference point. In a disease like Peyronie's, it is usually not "nothing" (ie a sugar pill) but the standard of care. I do not know if the control group in the Xiaflex study is getting Verapamil, but that would be an example of someone comparing new treatment B to standard treatment A.
The NIH does not make rules regarding this (though there are federal guidelines regarding research), but a study without a control group of some sort will not get funded, and usually not published. Except in this miserable field of research, where there are multiple studies of 15 or so men, without a control group, in paper after paper. Most of those papers I wouldn't use to wipe my ass.
Tim
Quote from: Tim468 on January 05, 2009, 05:03:58 PMI do not know if the control group in the Xiaflex study is getting Verapamil, but that would be an example of someone comparing new treatment B to standard treatment A.
Tim,
In your example of Verapamil possibly being used in the Xiaflex study. Would it be proper for them to refer to Verapamil as a "placebo" group or would the proper term for that be a "control" group?
I had the opportunity to participate in the Xiaflex trial study, but I turned it down because I already have a pronounced curve to the right, and I didn't want to take a chance on the needles worsening it. The participants who receive the placebo will be injected with Interferon, according to the literature I received.
Just thought I would let you know.
Bo
I'm in the Xiaflex trial and my understanding is that the placebo contains no drug of any kind. The written consent documentation states this in two different places, and additionally I asked the doctor and his study coordinator to confirm this, prior to my getting the first injection - they told me the placebo was essentially saline.
I don't know anything about the design of drug trials, but it seems it would be ridiculous to give the control group some other active drug - except perhaps if there were any already-accepted standard treatment that it would be valid to test against (from what I read here, it doesn't seem that there is any proven, accepted standard treatment for Peyronie's) . Anyway, in this case the consent documentation says that getting the placebo is like getting no treatment at all.
I also asked them, prior to getting the first injection, about potential harm if in the placebo group, just from the injection itself. The doctor told me that in the earlier phases of the trials, there were no adverse outcomes seen in anyone in the placebo groups. Of course I remain skeptical about this, but in the end you have to decide either you're going to do it or not.
Having been through one round of injections, my curve is completely unchanged - neither better nor worse. (which I'm not necessarily taking to mean I got the placebo, although that seems likely. I figure after the second round of injections I'll have a better idea - we'll see) (Also, as someone else mentioned here, the study is double-blind, so I don't think there's anything wrong with my posting limited comments like this, mid-study - no matter what opinion I state here, the fact is that I don't know which group I'm in)
G.
I know little to nothing about the actual parameters of the Xiaflex trials but I think I know the meaning of the word "placebo" and how it is used in clinical trials. A placebo is a substance that has no known therapeutic benefit or side effects. It is used in trials as a control to guard against "placebo effect" in which a patients perception influences the outcome. It also as Tim pointed out guards against some effect from the procedure (such as the injection) being credited to the drug.
As G. indicates, sometimes the control is an alternate standard of treatment rather than a placebo. I would surely think the participants of this study had full disclosure on whether they were signing up for a placebo based study or a control study based on a specific control drug that has known benefit and side-effects. I would even think this is a public information component of the study that we should all know by now. The guessing should be over at this point.
Rather than guessing, can someone settle this issue with authoritative evidence?
Were participants given copies of signed releases which shed light?
Are there published study guidelines?
Hawk,
I was given an Information and Consent Form to sign, which runs to 20 pages. I was given a hard copy to keep, and also have it on my PC in PDF form. I don't know whether or not this document is publicly available, therefore I don't know if it's appropriate for me to quote from it at any length, but here are the two relevant passages (by way of justifying my sharing them here, I'm assuming these are typical language for drug trials):
"As a participant in this study, you will receive either AA4500 or placebo (placebo looks like AA4500 but has no active drug) as injections into your penile plaque."
And later in the document, under the heading Placebo Risks: "Receiving placebo is the same as not receiving anything for your Peyronie's Disease."
hth,
G.
Quote from: Hawk on January 06, 2009, 04:06:29 PM
I know little to nothing about the actual parameters of the Xiaflex trials but I think I know the meaning of the word "placebo" and how it is used in clinical trials. A placebo is a substance that has no known therapeutic benefit or side effects. It is used in trials as a control to guard against "placebo effect" in which a patients perception influences the outcome. It also as Tim pointed out guards against some effect from the procedure (such as the injection) being credited to the drug.
As G. indicates, sometimes the control is an alternate standard of treatment rather than a placebo. I would surely think the participants of this study had full disclosure on whether they were signing up for a placebo based study or a control study based on a specific control drug that has known benefit and side-effects. I would even think this is a public information component of the study that we should all know by now. The guessing should be over at this point.
Rather than guessing, can someone settle this issue with authoritative evidence?
Were participants given copies of signed releases which shed light?
Are there published study guidelines?
Geez and all of this time I thought the "placebo" group was being forced to listen to the music of an overwrought tenor, truly an excruciating experience...
Sorry I could not resist.....
Quote from: G. on January 06, 2009, 07:41:16 PM
"As a participant in this study, you will receive either AA4500 or placebo (placebo looks like AA4500 but has no active drug) as injections into your penile plaque."
And later in the document, under the heading Placebo Risks: "Receiving placebo is the same as not receiving anything for your Peyronie's Disease."
Then it is conclusively answered. It is a
placebo - a substance not known to have any treatment benefits or any side effects. That would certainly not describe Verapamil or interferon.
Thank you G
Also it should be pointed out that the Xiaflex trial is currently a phase 2B trial, in which there is no direct comparison to a standard treatment. Therefore the placebo is a saline solution. When an investigational drug reaches phase 3, a head-to-head comparison is made with an established drug. In this case, it may very well be interferon or verapamil, but we are getting ahead of ourselves here. Let's hope that Xiaflex makes it that far!
Thanks RB,
Another excellent point that we should have picked up on. Comparisons to other treatments are only made in phase 3 trials.
It sounds like the Xiaflex study uses a true placebo for the control group. The terminology used is usually thus: the study drug group is compared to a control group. The control group may receive drugs (usually standard of care) or nothing (ie true placebo) if that is safe. In the case of Peyronie's, as many here have found out, doing nothing IS the standard of care and so doing nothing or a sham injection of saline is an ethical comparison group.
In other diseases (ie brain tumors) with some therapies available that are not good, then the control group usually gets the standard therapy, and the study group gets the study drug, or sometimes the standard therapy PLUS the study drug. The design of the study follows the available therapies, how dire the nature of the illness, and the risks of the study drug versus the risks of the control group therapy.
In Peyronie's Disease, some men here have reported having their Peyronie's triggered by injections, or made worse. But, in general, many men have had injections without problem. Also, given the questions raised by the hard-to-find reports about using the Leriche technique to treat plaque by loosening it up with a needle (I think they call it needle aponeurotomy, breaking up the plaque, in Dupuytren's Contracture), it is erasonable to hypothesize that the needle itself may have accounted for some of the improvement seen in Verapamil injections (and, I might add in the control group for that study).
Thus, it is reasonable that one have a small amount of saline injected into the plaque, in an identical manner as Xiaflex is injected, to allow the study docs to draw accurate and fair assessments of the drugs efficacy. It sucks to get placebo, but getting a good study done for a possible curative therapy (for some men) is worth the small risks some men face. Men given Xiaflex also face the possibility of worsening, or of nothing happening at all. If Xiaflex does one no more good than saline, then I would like to know it.
Tim
ps Phase 1 trials look at safety, and phase 2 studies look at dosing to help design a larger study. Phase 2 studies may include a control group and placebo.
Tim and RB,
Thanks for your posts - now I have a much better idea as to how these studies are designed.
Now let's just hope this stuff works!
G.
new to this forum...I have had two injections of xiaflex this week...hurts like h**l.....entire penis is black and blue...i can tell from the reaction that i got the real thing (i think the placebo is saline solution...). so - 2 injections this week. no idea what is happening to the plaque as i hurt too much to even think about touching it to find out. will post more as developments proceed...
Hey Barky,
Thanks for keeping us posted. I appreciate it. I am excited to hear what your experience is like.
Regards,
Ted
ted, you are welcome. one other thought - this stuff will be app'd for dupuytren's before it is approved for Peyronies Disease. doctors can use drugs "off-label" so probably some urologists will start using this once it get the app'l for dupuytren's.
Hey Barky,
Xiaflex can be used off-label. Insurance won't cover it... but I don't care. There are videos on google that show a woman's experience with Dupuytren's contacture and her result is AMAZING! She goes from crippled to functional. She was actually short of complete cure but she stopped because it hurt. The big difference is the degree of "manipulation." The doctors really, really, REALLY try to force the hand open. I guess it is hard to force the penis to that extent.
Keep us posted.
Ted
Is there anyone on this forum who is in the Xiaflex study who has noticed any improvement?
FYI - the fact that your penis is bruised is not an indication that you received the actual drug vs the placebo. Bruising is a result of the needle, not the medication.
I might add that bruising is of course bleeding internally in the tissue. Blood in tissue can possibly cause scaring. Do they apply direct pressure after the injections or instruct you to apply pressure? If so and you are not applying pressure for 10 minutes it may be worth asking about.
Ted,
Are you for sure that insurance would not cover off label Xiaflex? Wow, what a disappointment. I can't afford $10K for such a thing, and not sure that I'd want to ask my parents to spot me either.
I believe that I read somewhere that the treatment would cost between $ 4000-5000. Still expensive, but not 10K. Guys, I think we are getting ahead of ourselves, before getting our hopes up let's see what the study shows.
Just to support what Hawk said: when I got the first injection of the first round, they told me to apply pressure for a few minutes and I did so. And I had no bruising. When I got the second injection a couple of days later, I think they were in a hurry to get the next patient in, and they kind of hurried me to get dressed and get out of the room. And that is the one I got the terrible bruising after.
So I definitely learned my lesson, and am going to make sure I have proper time to apply pressure, next time.
Insurance companies typically don't cover the cost of off-label use of products. This is especially the case when a treatment for say, your hand is applied to your penis. The other thing that will likely come from this is that pain will be a requirement for certain insurance companies to cover the cost of the treatment. These are moves done by bean counting insurance companies to control costs. So, what we will probably see is a pre-authorization form for the use of Xiaflex. It will specifically indicate treatment of Duprentyn's contracture.
When the product is finally authorized by the FDA for the use in the penis, you will see all of the Peyronie's sufferers reporting "agonizing pain" as a result of the condition in order to get their insurance companies to cover.
Ted
Ted, Just a couple of comments regarding insurance issues.
1) With off label treatments a lot depends on the cost. This could be a real problem for Xiaflex. As the cost of a given treatment escalates, insurers get progressively more fussy about off label issues.
2) Another factor is who the doctor is that is prescribing the off label treatment. If the doctor is a member of the health plan in question, your chances for coverage are higher. If the doctor is a prestigious doctor AND a medical expert for your health plan, that boosts the potential for reimbursement even further.
Such has been my experience in the past.
- George
Or if he is willing to stretch the issue slightly to avoid the question. not saying I know of one that would do this, but ;) ;)
Anyone know if stimm cell research is being done to recreate tissue? Isnt Peyronies then one of the things it could solve?
"InterMune (ITMN) is expected to release Phase 3 results next month for pirfenidone in the treatment of idiopathic pulmonary fibrosis."
Source: multiple google news hits.
I say it's about time, and I hope that this may be able to replace Pentox in our routines.
Tim, given your background, do you think it is likely that this drug will be available to Peyronie's sufferers in America soon (i.e. this year)?
Once its FDA approved, it can be prescribed off label. The question then becomes who is going to prescribe it? Its a new drug with long term side effects not totally clear at this point. Will it be enough better than pentoxifylline to justify the risk? Doctors are going to think long and hard about issues like this. Additionally, pentoxifylline is dirt cheap, pirfenidone will likely cost a kings ransom. I can GUARANTEE you insurance companies won't pay. If you can, you MIGHT be able to get your hands on it. Whether or not it will be worth the extra cost remains a question. From my perspective, pentoxifylline combined with vitamin D does the job and I would be willing to wait a long time for something like pirfenidone. But to each his own. - George
Perfinidone isn't new. Intermune bought the rights to it years ago, intending to sit on it because they had their own, competing product. This inconvenienced a patient who was being kept alive by it; he sued and won a judgement against Intermune that forced them to begin trials of Perfinidone, and to continue to make it available to some number of patients. So the trials now being concluded were underaken only because of a judge's order. Whether Intermune actually intends to make the drug available remains to be seen.
http://www.thefreelibrary.com/Pulmonary+Fibrosis+Patient+Sues+InterMune,+Charging+Unlawful,+Unfair...-a096863347
We are now at the end of January. Shouldn't those in the Xiaflex trial have received the second series of injections by now? Can any report their results?
Did receive my second set of injections. Urologist said he detects a slight decrease in plaque size. I don't notice any difference in curvature, which is all that matters.
I received my second series of injections on Jan,13 &14.I am still sore.Was really black and blue this time.Way more than last time.I had very little or no swelling.I will be going to get measured Feb 12th but have not noticed any difference.sorry,Ticker
First of all, I want to say thanks to all of the trial participants who are posting here periodically. Even more so, I am thankful for those of you participating despite feeling that you are getting the saline injections! If Xiaflex ever hits the market for Peyronies Disease, it's because of people like you.
With that being said, we have yet to have a single trial participant say anything about any improvement whatsoever. It is disheartening to read these post knowing 2/3 of you should be getting Xiaflex injections! In the Dupuytrens trials, the effects were pretty dramatic and immediate...right? I guess statistically it is still possible that everyone that is posting here participating in the trial could be receiving the placebo injections. But there is little that I wouldn't give to see someone on here post a positive experience from the injections thus far!!
Correction to Roadblock - It is not 2/3 who are getting the drug, it is 3/4
Note to all:
Just had DC surgery thus past week. My surgeon was not aware of Xiaflex. He did the usual incision type repair.
He said that Xiaflex sounded like a good way to go and he would explore it and let me know what he found out. Maybe we can find something about it through his efforts.
Old Man
Hi everyone
This is my first post. I have been a "reader", like so many other members who post nothing, but read quietly looking for some kind of answer to their problem on this forum. I've read so much on what works/doesn't work, might work a little, etc. One day I saw the URL for the IIb Xiaflex trial posted on this site. I took a chance, found a location listed close by (85 miles each way) and called and asked to be admitted. I went for an interview, physical, detailed measurements, history etc., and was accepted! I had my first series of two injections, and subsequently felt that I was in the "placebo" group. There was no immediate reaction other than swelling and bruising. Nor was there anything positive thereafter. I had never been able to find a "plaque" anywhere, but the urologist I was assigned to, after a lot of squeezing/bending, found two! Enough said for my professional urologic abilities. I was again measured for amount of deviation, to see if I qualified for "round two", which consisted of injections 3 and 4, separated by one day. The Dr. injected into the original site for the third shot (where injections both #'s 1 and 2 were done) and the 4th injection went into the "other" plaque site (near the base, not the "bend"), as the Dr. felt that they were all related to the overall "distortion". Swelling and bruising followed, but when the discomfort subsided, I found a definite improvement in the "bend" in the erect state. The firmer the erection, the "straighter". I also found that my penis hung down more "straight" when flaccid, especially obvious when in the shower and well soaked in warm/hot water. I also found that the "hinge" to the right was MUCH less pronounced. Almost even resistance to deviation left and right, while initially at 3/4 from the base, it almost "fell" to the right, and resisted normally to the left. All of this to me indicates that Xiaflex has potential. I'll know more after (if?) I qualify for "round three", which is injections # 5 and 6. That qualification is based on measurements still to be taken to see how much deviation still exists. As I understand it, if a patient comes within 15 degrees of "straight", then they don't qualify to continue. More to follow if/when I "advance". Most participants in the trial are probably reluctant to post too much so as not to jeopardize their participation in the trial, myself included. I had to answer the post seeking more info from participants though, as others have already (courageously) posted. We all need some kind of affirmation in our struggle with this disease if something seems to show promise. As a layman, my thoughts are that when dosage and frequency are "dialed in", Xiaflex will be an answer, if not THE answer.
pjh,
On behalf of all other forum members, I thank you for posting your results.
I think we desperately need to know the potential of Xiaflex. Xiaflex is the only thing that holds me back from seriously considering surgery. I am willing to wait and suffer if I know that it will be a viable solution. Thus, hearing encouraging comments makes the wait less painful.
Thanks, and please post more!
pjh,
Thank you for sharing your results and experience. I assume you had to sign a confidentiality agreement before starting the trial, thus your statement about not posting "so as not to jeopardize their participation in the trial, myself included."
However, if you can do so safely, could you tell us how long you have had Peyronie's, your age, your degree of bend and curve before the injections, loss of length and girth, and anything you have done prior to the trial injections i.e. VED, traction, prescription drugs, vitamins, etc.
Thank you again.
As a trial participant and one who has had peripheral exposure to the process of bringing experimental drugs through clinical trials to market, let me say that we should all sit back and let the Xiaflex trial play out. First of all, this is a grand experiment. We do not really know what to expect in terms of improvement after all rounds of treatment have been concluded, much less one round. According to my doc, multiple injections may be required to observe any effect. Second, remember that 25% of us are receiving placebo, therefore there will surely be some non-improvers. Third, the trial participants do not represent a homogeneous group nor should it be. By that I mean, there are many different types of Peyronies Disease patients participating here. As an example, there are probably long-term and short-term Peyronies Disease participants in the trial (though all must be stable). Possibly there will an advantage for the short-termers based on having less plaque calcification (or not, who knows?). Maybe those with larger plaques will see a different level of improvement compared to those with smaller plaques. Age differences could be significant. This is what experimentation is all about. Let's be patient, as difficult as it certainly is for all of us.
My results so far after first round of injections---a slight improvement. Now awaiting the start of my second round. I am optimistic.
pjh,
Thanks also for posting. Glad to hear someone is seeing something positive out of this.
fwiw, I go in for second round of injections this coming week. No change at all after first round. As I posted previously, I'm not concluding yet, which group I may be in.
I asked the doctor last week if anyone in his trial was seeing improvement - he really didn't want to get into any detail at all, but with the stated proviso that he has no idea who is getting the drug and who is getting the placebo, he said yes, some people had improved so far - and he hastened to add, that some people improve spontaneously, anyway.
I think the key to posting impressions here, with all due discretion, is that this is a randomized, double-blind study. None of the participants nor the doctors, know who is getting the drug and who is getting the placebo. Therefore anyone posting their impressions here is doing so with the understanding that they really have no idea what group they are in, and won't until the study ends. It's also well-established that a fair percentage of Peyronie's patients see some improvement, without treatment, so a report here of improvement is still not necessarily evidence that this product is working - yet.
I'm not a lawyer, but I think the above provides a valid rationale for posting our impressions here. It's just conjecture, until the results are released. On the other hand, if a number of participants post here to the effect that they're seeing progress, well, that would be a real encouragement to everyone.
Attica - I haven't gone back and re-read the agreement lately, but I did read it twice before signing it originally, and I don't recall seeing anything about confidentiality. Again, just my opinion, but I think if we discreetly post our impressions in this members-only forum, I don't think we are violating any terms of agreement. Maybe Tim could comment more broadly on standards for participant confidentiality in these kinds of studies.
G.
From what I read, the Dupuytren's trials were quite successful BUT the treatment wasn't just Xiaflex. They injected a small amount of Xiaflex to weaken the cord at its midpoint, then applied a LOT of force - enough to finish the job by snapping the cord with an audible pop - and sometimes that hurt quite a it. Probably most of the fibrotic tissue unchanged, but snapping the cord in the middle was enough to release the finger.
Dupuytren's forms "cords" that in many cases are firmly attached at their endpoints but not in the middle. So if you sever the cord at its center, you restore range of motion. Peyronie's isn't like that, the affected tissue is more integrated with the surrounding, good tissue. There is no 'cord', just an area that's become stiff with collagen fibers.
I think the Xiaflex treatment for Peyronie's will be more effective if combined with traction and stretching - possibly immediately after the injection. I also think multiple injections over time may be needed, and more attention will have to be paid to the targeting and amounts. With luck, these issues will be worked out over time.
As always - just my own non-professional opinions.
j:
Had DC surgery on Friday, Jaanuary 23, 2009. Will see how mine works out. The doc did not know about Xiaflex or any other form of treatment.
Old Man
Hi all. Attica, in answer to your questions, no I don't remember a confidentiality agreement. I am just of the opinion that discussing personal results of a trial still in progress publicly could possibly antagonize the trial sponsors. Could that lead to expulsion? I hope not. This site is semi-public in that it isn't limited to professionals with a "need to know" or password only available to such types. It may be something of a risk to post, I assume. I took it based on a need to share info about our common problem that was only available from participants. Others had shared somewhat, and this forum is made up of people who share willingly what experience they have garnered over time. It was just my turn to step up to the plate, having never done so. Other answers: I'm 62 years old, and have had this curse for about four years. My degree of bend was 60 at the start of the trial. Length and girth wise, when this problem first occurred, I was taking Proscar for BPH for several years, and thought that the lack of DHT was causing something to happen "hormone wise" to me. Besides lousy orgasms, I found I was getting "smaller", like some kind of reverse puberty! I often wonder if Proscar (which I no longer take) was some kind of "trigger" for all of this. I mentioned this to the "trial urologist, but he said no. He also was reluctant (meanng "would not go there") to answer my question as to if any of his other participants were having any success or not. Things I've tried with no success: Vitamin E, oral, all forms, (tocotrienals, etc). Vitamin E oil applied topically simultaneously with DMSO. MSM, Quercetin/Bromelain, copper tablets, serrapeptase and nattokinase. BTW, once I had a "brainstorm" to break open the enteric coated serrapeptase capsules and apply it topically with DMSO. The idea was to get the serrapeptase to the plaque to dissolve it. BAD IDEA! Ulcerations followed, that it took my urologist to cure. I never tried any vacuum therapy or traction type devices. I was always afraid of doing further damage with them. Also, fwiw, I am not in the "modeling group" in the Xiaflex trial. Any other trial participants who wish to share their experiences so far, I'd like to know if they parallel mine, though I realize that there are many variations among us as relates to our common scourge.
G covered the issues well. As no one knows what they are getting, then their impressions here cannot (and will not) influence the outcomes of the study.
I have never had a patient sign a confidentiality agreement to participate in a study, though I guess that is done sometimes.
If someone came here and lambasted the company for how they do their research, that would be another issue - but still worth hearing about IMHO. What is reported here is ethical doctors doing ethical work - I kind of like it!
Tim
Old Man, what is DC surgery?
Ptolemy:
DC stands for Dupuytrens Contractures which is related to the symptoms of Peyronies Disease. The leaders/tendons in one's hands form a hard cord restricting the extension of the individual fingers. Surgery is performed to relieve the condition.
In my case, the ring and pinkie fingers on my left hand were drawn in so that I could only open my hand about 45 degrees, etc. After this heals, I should be able to open my hand all the way as before DC started.
DC, Peyronies Disease and Lederhose condition on feet are all related in one family of condition as per some doctors. I have all three. Peyronies Disease under control, Lederhose is increasing somewhat.
Regards, Old Man
Old Man, I likewise have all 3 and have had surgery for DC on both hands. Currently DC is attacking my left thumb and right index finger, and I expect to be looking for some sort of treatment before too long. I hope it will be Xiaflex.
I am not a trial participant, but for those who are interested, I have the Xiaflex trial agreement in PDF and can post it with this forum's administrator approval. It basically lays out all the details of this trial.
j:
Mine was so bad I could not straighten out my ring and pinkie finger enough to hardly pick up a glass.
Anyway, tomorrow we get the first bandages off to see how it came out.
Old Man
Quote from: Believer on January 25, 2009, 06:54:46 PM
I am not a trial participant, but for those who are interested, I have the Xiaflex trial agreement in PDF and can post it with this forum's administrator approval. It basically lays out all the details of this trial.
I assume it is a public document. If so, feel free to post it.
PS: Old Man, I hope you have a great outcome on the DC surgery.
Unfortunately the file is too large to post (1.1mb). If anyone wants it, just e-mail me at peyroniesqa@yahoo.com.
Gentlemen:
I was angry in my first post on this board. I realize I am an outsider and I have come into your domain. And my first contact with you is semi scolding the members here. When I first reviewed the boards here I got a little exasperated with what I see as the lack of mobilizing your efforts. I apologize to every member here for being disrespectful.
My husband has to have hope. And I am trying to give him hope. Three years of peyronie's has really hurt more than his penis. His spirit has been stripped from his personality. I am trying my best to be his advocate. His new hope is he will be accepted into a trial that fights tgf-beta.
Last week I went to the clinical trials link, searched for TGF-beta trials " http://clinicaltrials.gov/ct2/results?term=TGF-beta " to locate TGF-beta trials.
None of the trials were peyronie's related. That is shocking. Urologist are dragging their feet re peyronie's? So I have taken it upon myself to contact urologist, to make them aware of the trials and the drugs involved in the trials.
First I contacted uros affiliated with the universities and hospitals conducting the trials. Like I said, shockingly these uros are not even aware of the TGF-B trials at their own facilities. Why, I ask myself, don't they stay on top of their (game) and try and make headway against peyronie's? And that is where I come in. I am politely, respectfully keeping them aware of the challenges they need to get involved in fighting peyronies. I emphasize politely and respectfully otherwise they may view me as a reminder of how they are failing their practice and their patients. I also contacted uros not in the university/hospital circle of the trials.
I think I am making inroads by alerting doctors of the opportunity to get involved with these trials. When writing and phoning doctors I sometimes played on their opportunity to make a name for themselves among their peers by being in the vanguard of peyronie's treatment. If you gentlemen have additional ideas how to broach the topic with doctors lets share them now. And, most importantly, let's not let these ideas die on this board. Let's put them to work. Let's share them in our correspondence with the doctors we contact.
It always helps to be polite when speaking with doctor's and their assistants on the phone. So far a lot of them seem to be very receptive to the idea of starting their own trials. Will they follow up on that is the question. Maybe it will take members of this community to follow up with the doctors to keep this issue in their sights.
Using mail merge in Windows I use a form letter and insert individual doctors names into the letter. I mailed out letters to twenty urologists informing them of their chance to get involved in tgf-beta trials. It is my hope that a few doctors have the clout to start their own tgf-b peyronies trials.
So now my husband has more of a chance for serious treatment besides the anecdotal treatments currently available. Can I ask your support gentlemen. I ask you to help me and help the community by using your resources. I think I have laid out a respectful templet for keeping urologists in the vanguard of the promising treatments that are coming available every day.
Let's hear from you gentlemen. Who did you write this week? What material did you include in your packet to a particular uro. Maybe we can target a few specific uros to make more of an impact. We can make a difference.
Thank you and I hope you accept my apology.
HusbandsSppport:
Welcome to the forum. As you progress in your quest for help with Peyronies Disease, you will find out that Peyronies Disease and related men's health problems makes "strange befellows".
It seems that this subject has taken a back seat for centuries and breaking it out into the open medically will take time. Good luck to you on your efforts in helping your husband.
Regards, Old Man
husband's support, Fighting TGF-beta1 is definitely one of the current best ways to effectively deal with Peyronie's. But you need to be aware that there are already urologists offering a TGF-beta1 drug. That drug is Pentoxifylline aka Pentox or Trental. It is a TNF-alpha/TGF-beta1 inhibitor that is effective, inexpensive, easy to take and has few side effects. There is documentation on this site supporting its use in the treatment of Peyronie's. I recommend that you familiarize yourself with it and take steps to get your husband on it. It is also important to know that blocking TGF-beta1 will essentially stop the progression of the disease. It DOES NOT instantly reverse the damage already done. That can only occur by a natural process of healing that takes years. You also need to be aware that the use of a TGF-beta1 blocker does not fix the problem. It only patches the problem. It is my strong suspicion that the problem is caused by chronic vitamin D deficiency. There is a blood test that your husband's physician can perform to determine whether your husband is vitamin D deficient. My suggestion is that you familiarize yourself with this problem at http://www.vitamindcouncil.org (http://www.vitamindcouncil.org) and then discuss it with your husband's primary care physician. The Vitamin D Council is run by a team of top Vitamin D scientists and physician specialists. Be sure to note that the recommended level of Vitamin D is 50-80ng/ml, NOT the 20ng/ml which most labs show as normal. This is what is misleading many physicians to assume vitamin D levels are OK when they are not. New evidence is demonstrating these old recommended levels of 20ng/ml to be severely deficient and to have dire health consequences. I wish you the very best in dealing with this very frustrating disease. - George
Husbands Support,
Welcome to the forum. I am glad you returned to post. It was difficult to tell from your first post whether you were in fact a concerned spouse or a drive by bomb thrower with a fictitious persona. It seems clear from this post that you are a committed, articulate spouse that has experienced some of the same frustrations of most people dealing with this condition. I think I speak for the vast majority of members when I say that while your explanation and apology are appreciated and readily accepted, they are not necessary. We understand your frustration and your point.
I am very impressed with your commitment to translate your concern into practical action. While sharing ideas on the forum serves many objectives, your example of action is one we need more of. We have made several significant attempts to initiate an advocacy and awareness campaign but I can give us no better than a D- and that is being generous. I do think it is important that such action be well thought out and that it should be at least somewhat coordinated.
I will look at the link you provided on the TGF-Beta trial. I am also interested in seeing a copy of the letter you sent. You can send it to me via Personal Message (pm) if you like. I am also interested in some idea of how effective you found the results to be. Did you actually get any ear time with any urologist either in person or on the phone. Did you get any ear time from their staff? What was the response ratio and character of those responses etc? I think this information is valuable in assessing what works and what does not along with what just needs tweaked.
One thing is certain, such effort is very unlikely to decrease interest in Peyronies Disease and regardless of the level of success it likely does represent success on some level. Such an effort is much like sales. After you hone a good approach it is basically a numbers game. You have some ratio of success regardless of how high or low and you approach enough individuals to meet your goal. The fact that several ignore you or respond negatively is nothing but a statistical reality that you navigate as you work toward your goal. Simply put, every "NO" is positive because it gets you closer to the inevitable "Yes" you are looking for.
Thanks again for your return post. I hope you will not be a stranger here. Your views, your attitude, and especially your move to action rather than endless talk is a valuable contribution to the Peyronies Disease community.
Regards
Hawk
where are all the xiaflex guys? how's it going? there are 120 of you..speak up please! Thanks!
I got into the Xiaflex study right at the deadline so I just had my first set of 2 injections a little over a week ago (one on Tuesday 1/20 and one on Wednesday 1/21). The 1st went ok but after the 2nd my penis swelled up and was pink & purple. The Dr told me to apply pressure for 5 minutes after each but I guess I wasn't in the right spot the 2nd time. The bruising lasted almost a week but is now gone. If I touch the plaque it feels sore now like a bruise - never did before.
I haven't noticed any improvement yet, in fact it is slightly worse than before. So either it doesn't work quickly, doesn't work for everyone, or I got the placebo. I go back in a month for measurements and I'll update everyone on my progress.
Joe
thanks for posting joe
Joe,
you are a brave man! that does not sound like fun!
For some reason, my dr said applying pressure was not necessary. I have bruising, but no swelling. Not as bad as when I had the Verapamil injections and pressure was applied.
Don't think we are necessarily brave, just desperate for some improvement.
Had my 2nd set of injections a few weeks ago and no improvement noted in the curvature.
are you using any stretching with or after the injections?
Note to all:
Please be advised that based on my experience with verapamil and ED injections it is of utmost importance to apply pressure to the puncture site!!
Believe me, I know first hand about bruising, swelling and long time healing processes. Every doctor administering penile injections of any kind should advise patients receiving them to apply pressure after each shot
Old Man
to Jzyhawk - I am in the modeling group. twenty four hours after the last injection there is stretching
Peggy: In addition to the posts of the past couple of days, there were a couple of other posts about this, about a week ago - see in particular pjh's post from Jan 24 - that one is particularly interesting since he reports there was no improvement after the first round of injections, but improvement after the second round.
jayhawk: to clarify about the stretching (modeling) regimen (I'm in that group too): you're instructed to do the stretching 3x a day, during the duration of the trial. ohbj1's reference to stretching 24 hours after the second injection, refers to a scheduled follow-up visit where the doctor does the stretching on you - not sure why they schedule that - maybe to ensure that you are doing it correctly.
Joe: Thanks for posting. pjh's post indicates that sometimes it take more than one series of injections to see results, so hang in there.
Having just had my second series of injections, I'm starting to suspect a pattern in how people are reacting to the injection, and am starting to think that the 'hematoma due to not applying pressure' issue may be a red herring - based on my experience:
First round of injections:
1st injection: applied pressure afterwards. No swelling or bruising. Just a slight tender lump.
2nd injection (48 hours later): didn't apply as much pressure afterwards. Starting 1.5 hours after the injection, started feeling painful burning feeling on shaft. Shaft swelled up, ended up black and blue. Folks here, plus Dr. and study coordinator told me this was due to a hematoma and not necessarily evidence of reaction to the study drug, so I accepted that logic - until the second set of injections I just got this week. By the way, no change at all in curvature, after first round.
Second round of injections:
1st injection: applied firm pressure for 5 minutes afterwards. Like with first round, no swelling or bruising at all. Was very tender along entire shaft though.
2nd injection (24 hours later): again, applied firm pressure for 5 minutes afterwards. There was definitely no follow-up bleeding going on. However, like with first round, 1.5 hours after injection, began to feel painful burning feeling on shaft, which again swelled up. This time though, the whole swollen area was only pink - no sign of hematoma at all. However it was severely swollen and very painful. It was only when I woke up the next morning that it was black and blue - which I attribute to some capillaries breaking/leaking during erections I had overnight.
So this seems like a pattern: with or without the bleeding, the first injection in each series produced little reaction, whereas the second injection produced severe pain and swelling, eventually turning black and blue. At this point I'm starting to think that this is probably evidence of the study drug - I just can't see how I'd get this powerful a reaction, merely to injection of saline. The phrase "chemical surgery" came to mind, when I was in the midst of the worst swelling and pain.
48 hours after the second injection, saw the Dr. again for follow-up modeling session. I described the above to him. He's a pro and emphasized that he is 'totally blinded', but did allow that he is developing a 'suspicion' as to who is getting the study drug and who is not - based on the degree of severity of the reaction to the injections. I mentioned I'd heard that in some participants, improvement was not seen until after the second round, and he affirmed that he'd seen that. I told him there was still no change in my curvature, and he told me to keep my hopes up.
I'd meant to wait until the swelling/bruising reduced somewhat more before posting, but was prompted to do so now by the other recent posts. I'll report back later this coming week if there's any improvement once the bruising heals some more.
Good luck to everyone who is participating in the study.
G.
Okay...first post. Xiaflex study participant.
Completed my first set of injections this past week. Significant bruising after 1st set ..in spite of direct pressure for at least 40 minutes followed by a night of ice on dorsal plaque. Not in remodeling set. Additional swelling on pubic area and at area surrounding injection area...now 2 days after 2nd shot and just now noticing decreasing swelling. Hard to believe this reaction of swelling and discomfort over plaque is normal saline...but who knows? Everyone hopes for the med.
More to come.
bones54,
Thanks for posting. A quick question: When you had the reaction from the first set of injections, was the bruising and swelling seen immediately after the first injection, or did you not get that reaction until after the second injection? - am very curious to see whether there is any pattern to this.
Also, btw for what it's worth: the first time I had the swelling and bruising and spoke to my Dr.'s study coordinator to report that, she advised me to avoid using ice for the first 24 hours, to maximize the effectiveness of the drug - she advised tylenol but nothing else. You might want to confirm this with your Dr., but maybe something to keep in mind for next series.
G.
Each cycle consists of 2 injections which are spaced from 24-72 hours apart. Timing is based on patient preference and his reaction to the treatment. If there is significant pain, bruising or swelling the dr will wait until these symptoms improve. In my situation, I have had the injections 24 hours apart. The day after the first injection, there has not been any swelling, bruising and some minor pain. After the second injection, there was considerable bruising and some discomfort. Both were gone in less than a week. For those in the modeling group (I am in this group) 24 hours after the 2nd injection the dr performs the modeling (stretching) exercises. In theory, this will help to distribute the drug and assist in breaking up the plaque. Overall impression is that my urologist is very careful and the side effects of his treatment have been tolerable. But, then again there is no improvement after 2 cycles.
My experiences are in line with the last few postings. Second round completed. Not in modeling group. Swelling after 1st injection, but tolerable discomfort. But oh baby, it was a rough ride after the 2nd injection. Increased bruising and swelling laid me up for the entire next day. By two days post-2nd injection though, I was significantly improved. Same pattern occurred during my 1st round, so G, you are probably correct about a pattern. Interesting, my doc is not having me apply prolonged pressure after the injection. We will discuss this on round 3! I think I had a very slight improvement after round 1, and am optimistic about further improvements especially considering pjh's and G's posts. There is just no way that I am in placebo group given these responses to the injections.
Has anybody heard whether or not xiaflex will be offered to the placebo group after completion of the study, assuming a positive outcome for this trial?
RBW
RBWoodward - In answer to your question about receiving the placebo, cute and paste htttp://www.curepeyronies.net/index05Xiaflexupdatel.html
Ohjb1,
If you have a response from the xiaflex trial you want to cut and past on this site then feel free to do so.
This is the 3rd link of your website you have posted on this forum. As I recall you came here asking for money 30 minutes after you registered on this site. This link may refresh your memory. https://www.peyroniesforum.net/index.php/topic,639.msg12192/topicseen.html#msg12192
I suggest you read the entire topic if you have not done so!
You are getting very close to the point of looking like you are making unethical use of this site to promote your own activities. If you have any legitimate intentions you would not be spamming other sites and proceeding as you have done up until now. As a website owner you surely know proper internet etiquette for posting your links on other sites especially repeatedly posting them.
In case I have been too vague up until this point, your conduct is now resulting in an official public warning.
Hawk
Administrator
Ohbj1,
It is suspicious activity like this that leads one to say hmmm " Does this guy even have peyronies?" "Is he really in the xiaflex treatment study?" This is why we will have to wait for the final report on the clinical trials and trying to get answers off here may not be the best idea.
First, yes, I'm in the study. Because of postings I've read here, I made a point of confirming during my last visit (3rd round injections) to Dr Levine's office that placebo recipients will be offerred the opportunity to recieve the drug in the future. Further there is language in the consent form I signed that people that receive the placebo may be asked to be in another study where I would assume they would get the drug. I hope this information helps any participants that were feeling anxious about this aspect of the study. We are doing a good thing by being in this study, and as many have posted it hasn't been easy.
I have just finished reading the last month's worth of postings & I guess I could share my Xiaflex study experiences. I am 57 years old & I guess this all started a few years ago. To tell you the truth, I no longer remember if my onset was gradual or sudden, it just seems like it's been forever. I have around a 70-degree curvature with the "hour-glass" deformity. The plaque runs almost the entire length of the top of my penis, with a major nodule or two at the base. No erectile pain or pain during intercourse, though some sensation of "blocked" ejaculation. I feel I've had a major decrease in penile sensitivity, though I understand this could be a psychological side effect. I feel I need to use Viagra to maintain my erection during attempted intercourse and avoid "hinging". All this, along with my wife's normal age related sexual issues (decreased lubrication, dropped uterus floor), results in major impediments to penetration and sexual enjoyment. Masturbation is difficult because of the bend, but possible (especially with assistance of a soft flexible masturbator). I became a patient of Dr. Levine's because of his reputation with this disease and to get into this study.
Let me preface my description of my experience with the qualification that not everyone is going to have the same reactions, so don't read too much into this. I had my 3rd round of injections around the holidays. I don't know if this idea of reactions getting worse with each round is valid, but I can say I had my worst reaction after the 3rd round. Lots of bruising that then "dropped" into my scrotum :-\ and pain (this was the only round I ended up using an ice pack!). But I can also say I was distracted by a conversation during this round and was not paying full attention to applying pressure to the injection sight (wish I had read that tip earlier :( ). I am part of the modeling group. The modeling done in the doctor's office was painful, though I haven't needed to request a pain blocker. The modeling I do at home is not bad at all, bending while erect & pulling/stretching (though my wife says I've had my hand in my pants way too much ;D hey I'm just trying to follow instructions). I read with interest the comment about the severe bending that was/is part of the Dupuytrens Contractures treatment. That sort of coincided with another comment I read a while ago someplace that stated that men who re-injure their penis have a better chance to recover from Peyronies Disease. (Also thanks to "Old Man" for Lederhose reference - hadn't heard of that & think I have that - I'll have to mention at next visit.)
Before I mention any results, let me remind everyone that 1) I have no idea which group (drug/placebo) I'm in & 2) anyone who has seen significant improvement is probably not posting on this board, they're probably off enjoying a return to normalcy ;) That said, I think you can guess I've seen no improvement. However I think we need to remember that this study is not only about the drug, but the effectiveness of this course of treatment. It may turn out that the drug works, but needs to be administered differently in certain cases. I am still hopeful and positive about the drug. Hey, if this works, it's probably the best alternative available, but no one's going to know anything until they publish the results & that's a ways off. Unfortunately there is not going to be a definite answer tomorrow or next month or probably even this year. We need to be patient.
Finally, a comment on the comments about the surveys we're filling out. This is a necessary step in validating these questionnaires for future use in evaluating Peyronies Disease cases and helping doctors establish appropriate courses of treatment. They are not a waste of our time in any way, even though it may seem that way. It is a separate study from the drug study in my understanding.
Update.
Now 4 days after 2nd injection of 1st series. Swelling is better but still localized around base of penis and pubic area where marcaine was injected. Still quite sore to touch. Hard to tell what has happened to bend with erection as swelling is masking true shape. It seems as though I'm...shorter. I'm totally in denial though...willing to pass judgement when swelling is all gone.
Not sure if 6 weeks between injections will be enough to forget the pain. Local didnt work on second shot and even though volume of injection is tiny..and needle is tiny...it killed. What we dont do for science. :-\
has anyone else reached the last stage of injections?
If you go to the Auxilium website they report that Trial llb sign up is complete and all have had their first series of shots. They expect the results of the study my the 4th Quarter of 2009. Phase lll will not be expected to start until the middle of 2010 - Yes mid 2010. As I read the news report it looks as if Phase lll will use the Drug / Placebo in the study. My question is how are the one in the llb study group that received the Placebo be first in line to get the real drug and not the placebo again in phase lll ?????????
I don't think the drug will be used except in the Study Trials.
forget xiaflex - its too far down the track - it will never happen - stick with the ved and pentox - thats the reality and thats all there is to it!!!!!
Musicman - when a trial closes, it means that recruitment is over, not that data collection is over. The people just enrolled will get their injections over time, and be followed up, such that all should be done by the fall. Then getting that data collated and presented such that approval is forthcoming from the FDA for the next step takes time!
It is moving forward, at least.
Tim
Quote from: Iceman on February 02, 2009, 08:28:34 PM
forget xiaflex - its too far down the track - it will never happen ... thats the reality and thats all there is to it!!!!!
Iceman,
That is one absolute statement to be throwing out. Are you sure you would not like to qualify that statement. If you are willing to wager big bucks on that, then provide your case.
its just a gut feeling hawk - no cure for the past 250 yrs why would there be one now - plus im just venting frustration at the whole bloody thing!
Sometimes reading posts like the one below makes me want to pinch myself to see if I might be having a nightmare...
Iceman, for the next 2 years, we must be overly-optimistic. Let the trial run.
Why can we expect a cure? Well, for one thing - technology today never existed not just 250 years ago, but try 15! And if you recall, in 1992 or so, Verapamil was discovered. Yes it barely works - but still! Before Verapamil - people were limited to Vit. E!
Also - another reason for hope is globalization. Peyronie's is not just 1% of men now. It's more like 10% as more and more people speak up on forums like this one. 10% of the world's population of men is a lot!
Globalization allows doctors all over the world to exchange ideas easily. Levine, Lue and others are flying to Europe for lunch-and-learns and vice versa.
Human effort is the cure for Peyronies. Collagenase makes sense. I think we should remain optimistic. If nothing makes you feel better, consider this: if you it hits the fan - at least you have some hope. In less than 2 years you will know whether Xiaflex works. Only 5 years ago, people didn't even have that option.
Let's stay optimistic and focus on outreach. This forum needs to grow.
Iceman
I feel your frustration. But, we have to believe in progress. Myself at 66 people asked my why I opted for an implant, in just a few years there will most likely be a cure for ED. My responce was I don't have 10 years to wait.
If I was a younger man I would be right in the middle of any trial for this dread problem. For those in the trial I offer my support and well wishes.
Jackp
Looks like Intermune will be seriously marketing Pirfenidone. Their original competing drug - Actimmune - bombed in trials.
http://www.nytimes.com/2009/02/04/business/04lung.html?ref=business
Two comments regarding the article posted by j on Pirfenidone:
1) I couldn't help but notice that Viagra is being studied for the treatment of IPF. This leads me to believe that the value in a daily dose of Viagra or Cialis lies not only in the improvement of the ED but in the anti-inflammatory properties of the drug! This may also lead to strengthening of the association of Peyronies Disease and IPF as people from both sides explore possible treatment ideas.
2) Notice that Actimmune was largely prescribed off-label, and that this was a fairly accepted situation since there were no other treatment options. As the years go by, and pirfenidone (hopefully) builds momentum as well as a favorable side-effect profile, we may see doctors more willing to prescribe pirfenidone off-label for Peyronies Disease. The difference being that Peyronies Disease is not a life or death situation, no matter how distressing it is psychologically.
I'd also like to echo the sentiment towards the study participants that others have posted. I look forward to your accounts of what you are experiencing and what you are hearing from the urologists. Even though we have not seen much in the way progress YET, I'm still very hopeful and thankful for those of you sticking it out. Keep the info coming!
roadblock
Roadblock, you make some good points on the Viagra connection.
Was this an intentional pun?
Quote from: roadblock on February 03, 2009, 07:58:20 PM
I'm still very hopeful and thankful for those of you sticking it out.
;D
Quote from: jackp on February 03, 2009, 05:42:40 AM
Iceman
If I was a younger man I would be right in the middle of any trial for this dread problem. For those in the trial I offer my support and well wishes.
Jackp
After visiting 1 hateful GP, 2 hateful Uro's, and 1 uro who refused to give me anything besides "good luck" to help me I am disgusted with the whole thing. Are there any trials for venous leakage treatment? It appears not. Obviously I do not have simply venous leakage though and those of you who have followed my posts know that to be the case as well. Sometimes it feels like the pain will never be gone and I wonder about my future. I can't get involved in any study or anything that even has a chance of helping me because my doctors refuse to diagnose. Has anyone here been to Dr. Culley Carson and been given any other treatment or recommendations other than Trental and to wait? As my erectile dyfunction continues to worsen I am left with a sick and bitter taste in my mouth towards all the doctors I have seen over the last 8 months.
I've finishied all three series and wanted to report back to the group once things settled down and I had an idea of where I stood. Long story short I reduced the bend (more like angle for me) about 10% 10 degrees (corrected per writers later correction - hawk). I would be real surprised if I didn't get the real stuff. I had hoped the plaque would just melt like a pat of butter but it didn't (totally anyway). Still I think the glass is half full and Xiaflex is a good thing. I'm guessing I could probably benefit further with a few more series and I will definitely persue it when the approval comes for Dupuytrens. There will also be much learned how to optimise the treatments once all the data is in. I also think the drug company is mainly trying to show improvement without side effects and get the drug approved. Based on my experience, if I could pass on one thing it would to be optimistic but realistic. The success with Dupuytrens may not bring the same results with our disease. With Dupuytrens all they are doing is breaking a cord and stopping it from growing back. Peyronies involves more vital tissue and may be more like getting glue out of a sponge than just cutting a cord. I'm hearing others in the trials are making progress on reducing their bend but no miracle cures. I've also heard Xiaflex will do more to help a bend then a dent condition. It is not expected to help calcification. The injections also caused more of mental roller coaster than I expected. I'm pretty level headed but with all the bruising and swelling it was a little taxing wondering how things were going to turn out. I also had some swelling that caused me to think I made more progress than I did. You really need to wait at least 2 weeks before you have an idea if you made some progress. Keep in mind this is just my experience (everyone is different) and some unofficial feedback I've heard. I would encourage others to post but we should not draw any final conclusions until all the data is in. Hope this helps.
Quote from: Vernon21 on February 09, 2009, 01:12:51 AM
Peyronies involves more vital tissue and may be more like getting glue out of a sponge than just cutting a cord.
I like this description of Peyronies... glue in a sponge... although I wonder whether it's totally accurate. In Peyronies doesn't the glue
replace the sponge rather than just get inside it. So once the glue is removed there's nothing left? Hopefully I'm wrong, but maybe someone more qualified can clarify this.
Anyway, good to hear of your progress Vernon, and thanks very much for reporting back so eloquently.
I think Vernon made several good points and I agree with his point that Peyronies Disease may be a more complex issue to resolve than DC. I do think that typically the sponge analogy is a bit off.
Generally, Peyronies Disease is not scar tissue through the corpus cavernosum or spongy tissue that engorges with blood. It is scar tissue on the sheath (tunica). Because the sheath scaring cannot expand the sponge inside cannot expand, not vice versa.
Actually, I think Vernon is on the mark with his glue in a sponge analogy as long as one understands that the tunica, not the corpus, is the sponge, a sort of condum shaped sponge. Glycation works just that way. It causes tight disorganized crosslinks to form in the tissue making it stiff and inflexible. These crosslinks are formed out of protein and this is the structure that Xiaflex must dissolve. I also agree with Vernon that Xiaflex will not be a turnkey solution. It will be just another tool, a good tool, but not a complete solution. As for calcification, we already know that there have been multiple successes with Trental. So that base is already covered. The bottom line is that even with the strong headwind that is blowing in our direction in terms of Peyronie's research, progress IS being made and there are DEDICATED professionals out there giving it all on our behalf. Personally, I believe that at some point alagebrium is going to get approved and also be picked up eventually by some Peyronie's doc for off label evaluation. Alagebrium is an oral treatment that performs something of the same task as Xiaflex, although not as dramatically. But it IS systemic in nature which will offer yet another approach to a sticky problem. - George
I think Vernon21 is also right about Auxilium setting the bar low. They need to show only enough improvement to get approval, without unexpected side effects that become deal-breakers. So the treatment might be conservative. There are also limitations on time and money, so they probably can't run a long series of small injections, for example.
My Peyronie's is 'manageable' and actually I have a more urgent need for Dupuytren's treatment at this point, so I'll be seeking out a hand surgeon to hit me with Xiaflex as soon as it's available.
With DC, you can get rough. People in the Xiaflex trials for DC talked about the audible "pop" when the MD snapped the cord - and in some cases the very audible yell of pain that followed. Peyronie's will require a more sophisticated technique but we now have an agent which breaks up this collagen, surely there will be a way to use it more effectively than what is being done in these early trials.
Hawk, I understand what you are saying, but what's not clear in my mind is whether the scar tissue in Peyronies is additional tissue which has attached itself to the tunica, or is tunica tissue itself which has, by whatever process, turned into scar tissue.
If it's the former, once the scarring is removed the penis should, in theory, return to normal function. If the latter, once it's removed, by surgery, or Xiaflex, or whatever, surely there would be areas where there is no tunica, which I presume could lead to further problems i.e. leakage from the corpus cavernosum, leading to ED, for example.
I may be way off the mark with my suppositions here, of course.
Apologies if this question has been answered elsewhere on the forum. I've had a look around and can't see anything.
EDIT: I guess George has partially answered my question. It's still not clear though how viable the remaining organ would be once the scar tissue has gone, if there is no tunica either.
Shrout, Xiaflex is actually just a trade name for collagenase. You can look that up in Wikipedia. Collagenase is the same substance the body produces to prevent the uncontrolled proliferation of collagen. It doesn't "dissolve" the scar tissue, it "corrects" it and once its "corrected" by having the abnormal tight crosslinks removed, it normalizes itself and, to the degree it normalizes, resumes its usual thickness and suppleness. People get confused by the fact that in the case of Dupuytren's, the "cords" need to be "snapped". This is only because Xiaflex only partially does the job. If Xiaflex were to do the job completely, there would be no need to "snap" the "cords" because there would be no remaining "cords" to "snap". So we are talking about normalizing tissue by supplying collagen externally that the body is failing to provide on its own. There is no danger of melting away the tunica, but there might be untoward side effects from injecting too much collagenase although I don't know what they would be or even if the researchers know what they might be at this point. I too agree with Vernon. These docs are starting out VERY conservatively, because they would much prefer partial success to show stopper side effects. Once its approved, they are likely to get more aggressive and persistant. - George
Hawk is dead on and its good the scar tissue is on the tunica and not the corpus. If the tunica eventually totally becomes scar tissue the full penis size can not be realized in erection, but if this tissue is eventually disolved or reversed you can get your length back in theory. If the corpus turned into all scar tissue, it wouldn't expand at all and there'd be nothing to expand....
Have any of the study participants thought about what they're going to do next? As I've said elsewhere, I fairly sure (or at least very hopeful) that I got the placebo. BTW, Vernon21 congrats on seeing some improvement. If I read you correctly, I strongly agree that future treatment protocols with Xiaflex are a long way from being established. I think we'll see a much more aggressive treatment plan once the drug is approved.
Anyway, I was thinking I'll probably wait for the next study phase where I assume I'd be offered the drug, but that might not be for a year or more, right? I'm also afraid that if I tried any other treatment options, I would disqualify myself from future Xiaflex testing.
McNally
For me, I hope to hear more from others. While I think myself and others may benefit from some more Xiaflex injections, it still seems best to wait until all the data is in. I may not qualify for the open label trails but it is also quite possible that Xiaflex will be approved for Dupuytrens first. When that happens I will seriously discuss further treatments with my doctor (who is very experienced) on an off label basis. I am getting conflicting information if the first approval for Xiaflex is expected to be in Europe/UK or US. Has anyone heard anything more definite on this?
Also, in my earlier post perhaps I should have said "glue around a sponge" (maybe a bad analogy altogether). No need to belabor it, the point being I think there are more complexities to treating Peyronies tissue with Xiaflex than Dupuytrens tissue.
Vernon,
Was that a 10 percent or 10 degree improvement? Also, who was your doctor?
Thanks
It was 10 degrees, sorry for the error if I mistated it. I don't mean to sound cagey but until I am totally finished with all the required follow up, I would perfer not mention my doctor just yet. He is well known as an expert in this field.
Vernon,
No worries about the doc.
10 degrees is much better than 10 percent. I really hope that this thing hits the markets soon.
Thanks for asking so I could clear that up for everyone. I had an approximate 10 degree improvement not 10%. Must have been too focused on typing the message and had the wrong calibration stuck in my head. Sorry for any confusion.
Vernon - out of interest what was your starting point in degrees and I take it you were in a non-modelling group? Thanks
I was in the modeling group. I was closer to the lower threshold, 30 degree bend, required to qualify for the trails than the higher threshold which I think was 90 degrees.
Just thought I'd chime in to mention... it seems as of January 12th, Synvista has completed enrollement in it's Phase II trials for Alagebrium. This is great news. We can all keep our fingers crossed this works - although they're measuring for heart-related diseases, this will surely open the doors for ED testing, a field which Synvista has already held trials for with this same product! Xiaflex isn't the only treatment coming down the pike...
Just a random note on doing a trial...
Thinking about it (always a dangerous thing for me...), it seems that a variable in this study (Auxilium) is that A) the skill with which the plaque is injected may vary, B) the technique with which the modeling session is done by the Uro may vary and C) the techniques for modeling/stretching done by the patients may vary.
I suppose that if enough patients participate, that this should come out in the wash - should even out across centers. But a sub-analysis worth doing would be to see if there were any trends towards improvement by doctor, instead of by treatment. I hope they do that sub-analysis.
Tim
I have mentioned more than once how much I wish that we had a form of advocacy as potent and lively as the Cystic Fibrosis Foundation. This was started by the families and patients with CF, not by doctors (this is vital to remember) and they have help advance the cause of CF research greatly. How much I wish Peyronie's Disease had such a focus of funding, energy and institutional cooperation!
The messages we use to help remind patients as to why it is important to participate in clinical trials are pertinent to those of us here who have the opportunity to participate in such trials. I kow how frustrating it is to worry that one might be getting a placebo, but there are other compelling reasons for participation.
This is a good friend of mine talking about the research doctor's perspective, and why it is so important to those of us who do research that patients participate in trials.
http://www.youtube.com/watch?v=eMgaCbAN0K4&feature=channel
This is Boomer Esiason talking about the same thing, from the perspective of a father of an affected child
http://www.youtube.com/watch?v=do2KyqU6J4Y
Finally, here is a clip of a young girl herself. I hope that these clips serve to remind us why doing science is important, and why we must try to work together to lick this disease, er, beat this disease, er, dang!... well, you know what I mean!
http://www.youtube.com/watch?v=FxyxWJcw4rA&feature=channel
Tim
I certainly agree with what has been already said on the drug trial issue. In the case of both Xiaflex and Alagebrium, I believe the best shot here is just getting these drugs out the door in the first place. At that point, the owners of these drugs will be able to get them on the market and start to recoup their initial investment. Then there will likely be further trials and studies to refine treatment approaches AND explore new applications. Remember, once a drug is approved by the FDA, it really doesn't require a full blown trial to extend its applications and refine treatment approaches. Its safety has already been subject to scrutiny and the door is opened to judicious off label use. That is a major reason that companies are so conservative and risk averse in their initial trials. They just want to get their product on the market in the first place. AFTER THAT, their product can bloom and take root. Anything WE can do to get those innovative products over that initial hurdle will likely pay us all significant dividends in the future. Of course it would be nice to have a foundation at our disposal as well, but I think that many of us underestimate the value of this community and also of the professional community of which Drs Lue and Levine are a part. I think this actually gives us a leg up on some other very worthy patient groups that unfortunately are suffering irrelevance even worse than what we have to put up with. In the economy of this world, having any kind of "rare" disease is often a death sentence. Even though the cure my be relatively simple, no one is willing to put forward the capital to make it happen. Sad ... - George
quick update..going to have second round of xiaflex injections in 2 weeks...do not see any improvement...if you had me make a bet, I got the real thing...but maybe i should be hoping I got the placebo.
With regard to getting public support for research - CF affects the lungs of young children. Peyronies Disease affects the penises of older men. End of discussion.
I agree with George999, and hope he's right. Just injecting some Xiaflex into the plaque, somewhere, doesn't seem to be very effective. In my imagination I see some sort of time-release capsules embedded under the skin, releasing collagenase steadily over time.
"Just injecting some Xiaflex into the plaque, somewhere, doesn't seem to be very effective"
J,
Don't you think that statement is a bit premature? We are going based off of what people on this forum are telling us, and they don't even know if they have placebo or not? I to share your skepticism, on the other hand we didn't go through the full trials with a report yet.
Comebackid
You're right, it's too soon to say anything, especially if the injection causes temporary bruising and swelling. I still think this stuff will work for Peyronies Disease because it's already working for Dupuytren's. What I should have said was that a simple injection may not turn out to be the most effective way to use it.
Sometimes one just has to dream. According to this paper (http://www.jbjs.org.uk/cgi/reprint/85-B/4/469.pdf),
Quote from: The Journal of Bone & Joint SurgeryPrevious reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren's disease and it has even been suggested that this condition is a T-cell-mediated auto-immune phenomenon. Gudmundsson et al investigated subsets of peripheral blood lymphocytes from 21 patients and compared them with those of ten healthy blood donors and found that the Dupuytren patients had an increase in DR+ T-cells when compared with the control group. They considered that these findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren's disease.
What a fascinating little piece of information. The probability that B-cells are involved in Dupuytrens's and, thus, probably in Peyronie's as well. IF that be the case, one has to wonder what might happen if a Peyronie's patient were treated with a drug that knocks out B-cells. A drug such as the mono-clonal antibody Rituximab (http://en.wikipedia.org/wiki/Rituximab). I wonder! - George
Quote from: George999 on February 23, 2009, 08:55:14 PM
Sometimes one just has to dream. According to this paper (http://www.jbjs.org.uk/cgi/reprint/85-B/4/469.pdf),
Quote from: The Journal of Bone & Joint SurgeryPrevious reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren's disease and it has even been suggested that this condition is a T-cell-mediated auto-immune phenomenon. Gudmundsson et al investigated subsets of peripheral blood lymphocytes from 21 patients and compared them with those of ten healthy blood donors and found that the Dupuytren patients had an increase in DR+ T-cells when compared with the control group. They considered that these findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren's disease.
What a fascinating little piece of information. The probability that B-cells are involved in Dupuytrens's and, thus, probably in Peyronie's as well. IF that be the case, one has to wonder what might happen if a Peyronie's patient were treated with a drug that knocks out B-cells. A drug such as the mono-clonal antibody Rituximab (http://en.wikipedia.org/wiki/Rituximab). I wonder! - George
so who wants to give that a shot?
Along those same lines, what about something like Orencia as well?
Quote
T-cell Costimulatory blockade
Abatacept (Orencia®)
Abatacept is the first of a class of agents known as T-cell costimulatory blockers. These agent interfere with the interactions between antigen-presenting cells and T lymphocytes and affect early stages in the pathogenic cascade of events in rheumatoid arthritis. T lymphocytes become activated due to an unknown stimulus but likely involving the interaction between antigen presented in the context of the Class II Major Histocompatability Complex molecule on the surface of antigen presenting cells. T cells recognize antigens as foreign and if they receive a second stimulus, will become active, proliferate, traffic to inflamed sites, and secrete proinflammatory cytokines including TNF. One of the important second signals for T cell activation is mediated by the molecules CD80 and CD86 found on antigen presenting cells and the CD28 molecule on the T cell surface.
Mechanism of action:
Abatacept is a fusion protein that combines the extracellular domain of the molecule CTLA4 (CD154) with the Fc portion of a human immunoglobulin molecule. CTLA4 has very high affinity for CD28. When abatacept binds to CD28 on the T cell surface, it prevents the second signal from being delivered, thus turning down the T cell response. Additional effects are decreasing the production of T cell derived cytokines including TNF.
Dosing:
Abatacept is administered via intravenous infusion once per month after initial doses at baseline, 2 weeks, and 4 weeks. The dose is based on body weight, with patients <60 kg receiving 500 mg, 60-100 kg receiving 750 mg, and >100 kg receiving 1000 mg. The medication is administered over a period of approximately 30 minutes to one hour.
Time to Effect:
Responses are typically seen within 3 months. In clinical trials, patients with initial responses continued to show improvements through the first year.
Adverse effects:
As with other biological DMARDS infections are increased in patients receiving abatacept. These have ranged from mild to severe. Respiratory infections including pneumonia were more common in clinical trials in patients with underlying COPD, thus extreme caution is suggested in this population. Malignancies have been seen in clinical trials but it is unclear if the rates are more that expected in patients with rheumatoid arthritis.
Opportunistic infections have been seen, though only a few cases of TB have been seen to date. Infusion reactions have been seen in clinical trials that are typically mild.
Maybe I'm misreading the wiki on this drug you posted, George, but among other nastiness it can cause a side effect of "Progressive multifocal leukoencephalopathy" that turns the white matter in your brain into swiss cheese?
I'll take a bent penis over not being able to talk or cognitively reason, if that's the case.
When we give Rituximab to our transplant patients, we keep our fingers crossed it will make them better and not worse.
Count me out!
Tim
Quote from: Tim468 on February 25, 2009, 02:45:39 PM
When we give Rituximab to our transplant patients, we keep our fingers crossed it will make them better and not worse.
Count me out!
Tim
Good point! ::)
Correct me if I am wrong. Xiaflex is in Phase III trials for the treatment of Duyputren's Contracture in the US. But it has completed the European equivalent of Phase III trials and is expected to be approved in Europe later this year and on the market there in 2010.
Does anyone know at what point are the trials for Peyonie's in Europe and the timeframe for it's debut on the market? It appears to me that the US is slower in its approval process and it will be several years before we can expect Xiaflex to be approved for Peyronies Disease here.
Also, I understand that the cost of treatment with Xiaflex is more than surgical options. As such, insurance compaines may not approve treatment with Xiaflex and certainly won't approve an off label use of it to treat Peyronies Disease.
I feel like I've just been punched in the stomach. I had gotten my hopes up that Xiaflex would be on the market by the end of this year.
Quote from: Gregory on February 25, 2009, 04:17:34 PM
I feel like I've just been punched in the stomach. I had gotten my hopes up that Xiaflex would be on the market by the end of this year.
Greg,
They are having trials to see IF it passes. While hope is good, we have to be realistic. Data must be analyzed, and FDA decision made, marketing will begin and that is assuming the trial comes out the way we hope.
I think it is premature to think this is going to happen in the next few months,
QuoteWhat I should have said was that a simple injection may not turn out to be the most effective way to use it.
As a study participant, my impression is that the current Xiaflex study is taking a very conservative approach to the injection protocol, and that if it's approved a more aggressive injection schedule might be used.
to market by next year?
doubt it. being in the study, they will be observing/measuring for the next 9 months...
maybe 2 years--if its effective.
Gregory, I think the cost of Xiaflex treatment has yet to be worked out. What we've heard so far are the wild revenue projections Auxilium has given to prospective investors. Their presentations have crowed about how Xiaflex will command "a premium price" (their language) because it's supposedly the only alternative to surgery for Dupuytren's. The latter statement is not true - there's an excellent non-surgical techinque called "needle aponeurotomy" that's gaining in popularity. The former statement may not turn out to be true either.
Auxilium has to come to terms with the insurers if they want a market for the product.
Yes, I guess I am overly optimistic and I have to hold on to some hope. This has been doubly devastating for me. First, to have deal with prostate cancer and the side effects of that and then to be hit with Peyronies Disease on top of it. I am blessed that the cancer seems to be gone. Jury is still out on that. I hasn't been two years yet after my surgery. I knew I'd have to deal with ED issues but given the alternative, I chose a life of possible drug or injection induced erections rather than no life at all.
I was so excited to see that there is a good possibility of a good treatment if not an outright cure in Xiaflex. I feel like a little kid waiting for Christmas to come and the wait is painful. I know that there has to be sufficient research and trials to measure efficacy and safety. I just wish that this would get moved along quickly. Some stats say this affect 1%, others as much as 5%. Those are still big numbers when you think about it. The emotional side of it needs to be factored into just how serious this is. I don't want to hear, "oh, it's only a penis. Get over it." I realize more than ever just how important a penis is, not only to the man, but to the woman or partner and that relationship. Our sex lives are important to our wellbeing. This is a cruel disease that causes so much pain.
As for the cost, well, the price will be determined on what the market will bear. How much would any of us be willing to pay to have this curse taken away?
Greg
Then if i'm reading you correctly, your saying in all likelihood the price of xiaflex will be cheaper than the exaggerated claims made by auxillium? They aren't going to tell investors "yeah we got a great product and we want to sell it at a dirt cheap price." I totally read you on this one. Its like the last company I worked for crowed to investors and shareholders that we sold an "incredible service," which allowed us to get "premium prices for our goods." Despite the fact that the competition was selling the same products at 25% cheaper than us. Its all jibberish bs talk to keep greedy investors happy. I'd just ignore it. Personally I'm just interested in hearing about the actual study results to see if the product WORKS. I'm sure it will be somewhat expensive, but i'm sure most guys wont mind taking out a credit card loan to get the treatment if its proven to work.
Comebackid
Gregory: "I don't want to hear, "oh, it's only a penis. Get over it." "
You won't hear that on this web site!
I expect that it will help some men, and it will be hyped, and it will not help others and when the dust settles, the price will too. To be competitive, it HAS to be an alternative to surgery, and it has to be cheaper.
Tim
Companies like Auxilium do need to beat the drums to get investment money, otherwise nothing ever happens - no Xiaflex. I did however find their use of the term "premium price" a bit grating. It implies that they think they can really shake down patients, who have no other option. It's not something they should have said out loud, or in print.
Peyronie's surgery has a relatively poor track record. So if Xiaflex actually worked in, say, 60% of the cases and at least did no damage to the other 40%, you could say it's "better". Does that mean it should cost more? How does "supply and demand" play out here? What would the insurers decide? Do they get to see Auxilium's books so they know the real cost of production? I don't know.
The reality though is that Xiaflex is a product, and there's a market for it, and a price will be found.
I imagine that price will be found at a patients willingness to spend money to cure their penis, and take away all the emotional suffering we have bottled up inside. This is assuming the product works on most people. I imagine a lot of people would probably be willing to take out a $5,000 credit card loan to pay for treatment, if there was promise. I'm sure the price will be high, I don't worry about that, I worry will the product actually work? There are no other real treatments in the pipeline, so for now I keep taking my pentox like candy!
Comebackid
i really feel like i am improving and its not imaginary - the other night after ved usage i could see that it was straighter and longer - i really believe that its a combination of 1 year on pentox 3 times a day and daily usage of ved - i even took it overseas with me - i very diligent like that - using ALC plus l argine and lately tribulus may have helped as well - but i will keep on pumping and taking pentox till there is something else as I an crap scared that the pain will one day return .
personally i don't see myself pumping the VED and taking pentox in 2-3 years time. if things don't resolve then I will schedule for Surgery.
I'm not telling you what to do with your penis, you have a choice in what happens to it, the decision is up to you. Personally though pentox is really the only treatment that has been proven(even if its unscientific) to actually cure or help improve peyronies conditions. I would only get surgery if it was absolutely necessary, otherwise surgery can go wrong and create more scar tissue. I'd easily take a pill for two years, and intend to keep doing it this time, why not?
Comebackid
To me it comes down to how long are you willing to wait. Pentox did nothing for me after a year and that was enough for me. There is some data in the "surgery" thread that indicated to me that the risks are lower today with surgery than it was say 10 years ago. And then it comes down to the actual surgeon and their experience.
If one is seeing improvement from Pentox or any other therapy, then stick with it. But when nothing else works how long are you willing to wait and live with your current condition.
Quoteimagine a lot of people would probably be willing to take out a $5,000 credit card loan to pay for treatment, if there was promise.
very interesting - when pressed, $5K is exactly the figure my wife came up with to "what would you pay out of pocket to cure this" - personally, that's cheap at twice the price (LOL - sort of).
Guys - Not so loud, please, Auxilium will hear you - and guess what the price will be...? :)
Let them hear - that's the point. If Xiaflex works, I will buy it with ANY price tag. If it means I have to be an indentured servant for 20 years, let it be so. Show me a man on this forum, who will say "I think sex isn't worth that much."
I've been doing some cursory looking into about a possible connection to propecia use and Peyronies Disease affecting young men, as I'm in my 20's and it seems other posters of a young age have reported using finasteride before they developd this horrible condition, like me.
I took a look at propeciahelp.com, which has a lot of good forums about it (and they even mention this community favorably on their Peyronie's board). One link I found paticularly interesting, and hadn't seen referenced here:
http://www.propeciahelp.com/forum/viewtopic.php?t=346
and the source: http://contemporaryurology.com/conturo/article/articleDetail.jsp?id=111998
I leave the first link in because it's a long interview and the original poster highlighted the pertinent information. It regards the use of androgen replacement, seperate from testosterone replacement, as the new wave of treatments that will supplant surgery. I'm not sure if these guys are overly optimistic or what - but I figured with other eyes on it maybe it can make a little more sense.
Apologies if this link is already known.
Ocelot, I think this is a very promising piece to the puzzle. I would certainly like to read more, but the interview in question is restricted to subscribers to the ModernMedicine site. So there is no access to the content for non-subscribers and it appears that subscribers must be medical professionals. BUT note that this is NOT about testosterone, it is about ANDROGENS, and one would have to read the interview to know what they are doing with this. That said, I have long believed that out of whack hormones have a whole lot to do with Peyronie's. I also believe that the autoimmune process involved, TGF-beta1 etc., is hormonally driven. - George
J
QuotePeyronie's surgery has a relatively poor track record. So if Xiaflex actually worked in, say, 60% of the cases and at least did no damage to the other 40%, you could say it's "better".
I know some here on this forum have had negative experiences with surgeries. But some of these were combined with implant, prostatectomies, or other related issues. I have to admit I'm a bit of an advocate for surgery under the right conditions and as a last resort if other therapies have failed. I've posted this before but let me repeat some documented statistics in favor of surgery.
Dr. Levine has just completed a 14 year study that was just submitted and accepted by the AMA. The study was for 120 men who had undergone surgery for Peyronies Disease. The follow up has been in progress over the 14 year period. My wife and I tried to write this all down after the fact and hope we got most of the numbers close.
1. None of them required a second procedure.
2. 30% of them had some decreased feeling, but some thought this an advantage as they were able to "last longer" for their partners.
3. 20% (I think) had some increased ED in their ability to achieve a firm erection, but all these were treated through the use of drugs like viagra.
4. 5-10% had some recurrence of curvature but not near like they had prior to surgery.
5. (And the one I find important) ALL men were still able to climax and ejaculate during intercourse.
http://www.marketwire.com/press-release/Auxilium-Pharmaceuticals-Inc-NASDAQ-AUXL-956331.html
lwillisjr - thanks for posting that information. It has to be encouraging to anyone thinking of going that route.
Those are really good numbers, I can't dispute what Levine says, but I retain some skepticism based on my experience with 2 Dupuytren's surgeries. I felt they were somewhat oversold with regard to results, and the surgeon's evaluation of the final result was overly positive. Actually what happened was that during the final visit he looked at my hand, said goodbye and headed out into the hall where he dictated his findings into a pocket recorder - which I overheard. The actual result wasn't as great as what he described. And within a year there'd been considerable regression, which wasn't captured by any followup.
I think guys should believe Levine's results, but keep in mind that studies like this may tend to emphasize the positives. Surgery is, after all, just a service being marketed.
I read the report on Xiaflex go for FDA approval. I am not sure if I understand if it could be 60 days or the FDA has up to 6 months to decide?
Perhaps Tim or J, or someone with some FDA knowledge could give a brief summary of how the process works for us non FDA approval people :D
Comebackid
Not sure I can explain the FDA process, but I will see if I can create a good and short explanation of how it works.
Tim
Thats kind of what I was hoping for a summary , maybe step by step, you can cut out all the bu@#$@#it information we don't need.
Comebackid
I am in the Auxilium study and just received my second set of injections this past Tuesday & Wednesday. After the first set of injections I didn't see any real change so I was thinking I may be getting the placebo.
I woke up in the middle of the night this Wednesday (after my last injection) in extreme pain. I had a nighttime erection and it felt like someone was ripping my penis off. It has felt bruised all week. This morning (Sunday) I woke up with a semi rigid erection, and felt no pain. I started kissing my girlfriend, thinking I was now ok, but when I got a little harder I was in agony again. My flacid penis is now purple, swollen, and tender.
I didn't feel anything like this after the first set of injections. I am optimistically thinking that maybe I got the real drug, and it is starting to work.. Similar to the Dupuytren's cases where the Doctor snaps the cord after the injection, I thought maybe the pain is the plaque being torn naturally by my erection. Does this make sense? Anyone else in the study feeling this level of pain? Or should I be worried and call the study Doctor tomorrow? (I will probably call anyway)
-Joe
Joe,
You probably want to call your doctor just to make sure this a normal response. Man we haven't heard a lot of good results from people in the auxillium study, this is getting depressing! I don't like the idea of injecting anything into the penis unless you know it will dissolve the fibrosis, then it will most likely offset any damage caused by the injection itself. On the other hand, it could be the drug is working, it just may be a painful process to get rid of the plaque, that stuff is hard and may be tough to break up and dissolve. Keep us posted on what your doctor tells you and if it gets any better.
Comebackid
Joe,
I would call the doctor. If you were supposed to have pain or if there was a possibility of it, then he should have told you. In the absence of a warning, I would think pain is not normal and you should call him. I hope your theory is correct that the erection is causing the plaque to break up. Keep us informed.
Greg
Joe,
Definitely check in with your doctor tomorrow, but for what it's worth, pain and bruising doesn't seem to be an unusual reaction. My reaction was a little different from yours (bad bruising after first round, really bad bruising similar to what you describe after second round, and both times, the pain and bruising started about 1 to 2 hours after the second injection of each round). The condition you describe being in now, sounds really familiar. If it's any consolation, it might mean it's more likely you're getting the real stuff.
G.
The MDs don't really know what to expect, it's a new procedure and the patients will have to report what happens. In the Dupuytren's trials I think there was a farir amount of temporary bruising and swelling afterwards. I assume the same would happen here so if you get an erection, it could hurt.
Quote from: ComeBacKid on March 08, 2009, 03:15:23 PM
Man we haven't heard a lot of good results from people in the auxillium study, this is getting depressing!
Reports at this point are utterly meaningless. Multiply meaningless by ten since know one has a clue if they are getting the drug or not.
I would think that penile tissue undergoing severe treatment like this needs to left alone until a great deal of time has passed. If there is any chance that healing may be adversely affected by erections during the crucial period, then shouldn't erections really be deliberately prevented? (There are medications for that.) The long-term benefits of increased blood flow from erections can surely be deferred for a while without permanent consequences, in the interest of letting the collegenase work without backfiring.
The pain should serve as a reminder of that risk. With my series of a dozen Verapamil injections (largely unproductive), I had nothing like the pain these trial patients are reporting, except briefly around the actual time of the injection of the substance and the manipulation applied to distribute it through the affected area. I hope I'm wrong, but we already know how easy it is for the scarring process to start. even with no apparent provocation. So I would be hesitant to let the tissue get worked up or inflated while still under critical reconstruction, any more than you would run a marathon with a cast on your leg or while still being treated for a heart attack.
My doctor said that a certain amount of discomfort and and bruising is to be expected and most likely indicates the real drug. Also, it can indicate some of the tissue is releasing so it is not necessarily bad. I may be similar to what they are trying accomplish with modeling.
I would be very careful not to prejudge the reports here. Breaking up established plaque in a short amount of time is unprecedented and is likely to be traumatic. It could just as easily turn out to be highly positive in terms of outcome as to be negative. How these patients proceed in the light of these traumatic outcomes would be best left to the judgement of their physicians. In any case, I believe they should be staying in close communication with their doctors since they are really in uncharted territory. - George
QuoteI started kissing my girlfriend, thinking I was now ok,
Joe, for what it is worth, I was told no sexual intercourse for 2 weeks after the last injection in a cycle (& to be honest, I really didn't feel like it anyway because of the tenderness). But I don't know that we are all getting the same instructions.
QuoteI was told no sexual intercourse for 2 weeks after the last injection in a cycle
I guess I forgot since I was only bruised for a day or two after the first set of injections and then had no pain. I wasn't really trying to initiate sex, just kissing and got a painful erection (I will definitely avoid that now). The first time several days ago was a nocturnal erection that I had no control over though. I called today and spoke to the study coordinator - she said she'd relay my worries to the Doctor but that they have heard a few similar reports and that it is normal. She reminded me of the no sex for 2 weeks instruction. I apologize if I am lowering anyone hopes of the drug or anything like that. As has been said it is really too early even for me to tell and I don't even know if I am getting the real thing.
-Joe
I am not a doctor, nor do I play one on tv, but I was curious if any of you learned gentlemen could impart some medically based opinion on what the lifting of the ban on stem cell research may impart for peyronie's.
Stem cell research is more or less an investment in the future rather than applicable technologies available today. This technology is in an early stage. There are "moral" arguments (that center mostly around anti- abortion stances) that worked to hamper that emerging research under the previous US administration - but elsewhere in the world no such restrictions existed, and there are many private interests that were not hampered by the public policy. So research was not stopped completely - it was only deprived of certain avenues of funding.
I wouldn't go so far to say that Mr. Obama's stance will lead to a panacea for human ailments, but it's opening up a rather large pipeline of funds to what many agree is the most exciting line of research of our generation. I'm not an expert on this, but it's certainly an exciting development. More money means faster research and more laboratories getting funding. That can only be a good thing.
In fact stem cell research has never stopped in the U.S. This has been an emotional issue in which both sides often tune out facts and take an emotional ride. There is much research on stem cells that have nothing to do with embryonic stem cells. In fact advances have made it clear that non-embryonic stem cells have shown value that was thought only to apply to those from embryos. These advances have reduced the importance of embryonic stem cell lines.
Furthermore, embryonic stem cell research continued uninterrupted. The restriction was only on newly generated lines of embryonic stem cells. Research on existing lines has been ongoing
well, no change, still 70+ degree curve, still hourglass deformity :-\
I still think (hope, because that explains the lack of improvement) I'm on the placebo but will not be able to find out until October - I was told that while the study has not been completed, there has been no noticed correlation between "bruising" and anything else
one more visit to go - 36 weeks & I believe that one includes an ultrasound
btw, was anyone else in the study asked to sign a "revised" consent form?
Revised consent forms are often created because of some committee finding an objectionable term, changing the wording, and making the investigator change it. I recently had to change a form that did not specify exactly who would tell a parent about a pregnancy if it occurred.
Tim
By this time most that are in the phase IIb trial have had their 3 rounds of injections of Xiaflex. Can anyone state that they have had s 90% improvement with a bend of 50 - 60 deg? Please send a pm to me, just for my own information on progress. Musicman
In regards to MUSICMAN's comment, if anyone has seen that good of improvement, please post it on here for us who are awaiting the results!
I have heard unofficially of a 25 degree improvement on an approximately 45 degree bend. My contact mentioned there have been other improvements but I didn't get specifics. While it seems there have been improvements, I have not heard of any 100%s, more like a good improvement is a 40-50% reduction over the original bend. Again, this is just anecdotal and not at all scientific. There may be many other better reports yet to be heard. I will be back to the doc next month and will ask more, but we should all wait for complete results before passing judgement.
This is definitely very good news ... but ... I think the big question here is whether or not this is a lasting fix. If it is a lasting fix, in other words, if things are still roughly the same or better five years from now, then we have a 'keeper', otherwise, not so good. And if things stay better for five years, then they will be looking at the potential benefit of a tiered therapy, ie can we get another 50% out of a second treatment (which brings us to 75%) and then perhaps a third round which would effectively cure the problem for most people. But there are still a lot of unanswered questions. - George
Quote from: Vernon21 on March 25, 2009, 02:52:24 PM
I have heard unofficially of a 25 degree improvement on an approximately 45 degree bend. My contact mentioned there have been other improvements but I didn't get specifics. While it seems there have been improvements, I have not heard of any 100%s, more like a good improvement is a 40-50% reduction over the original bend. Again, this is just anecdotal and not at all scientific. There may be many other better reports yet to be heard. I will be back to the doc next month and will ask more, but we should all wait for complete results before passing judgement.
All in all the results sound like a bit of a mixed bag. I wonder if those researching the use for peyronies, will see the results as positive overall.
In reply to George's thinking is is good news I am not so sure. If a person gets 25% improvement on a 45 deg
bend that still leaves a lot of angle to the dangle. If a person has 80 deg bend he still has lots of problems.
If you have 35 deg bend 25% sounds good. Sure more injections down the road might bring more improvement but that time line is a long way off. Remember phase III will not start until mid 2010 and then a
good deal of time to get drug to market. People on this forum are in various age groups. I for one don't think
I will live long enough to see the full benefit. If I do live that long there might not be a purpose of needing the treatment anyway. Some here with a small bend think they have a big problem, if they had a big bend
then they would know what a problem really is. With the talk of supplements, ved, traction, and so one this is
good for the 30 deg guy but don't feel it will do much for the 80 deg guy. I would make my appointment today for surgery but I am not in a position to financial do it. Stuck between the rock like they say.
Now two weeks past my third series of injections, and unfortunately nothing encouraging to report. I had moderate to severe swelling and bruising after each series of injections, which led me to suspect I was getting the real thing and not placebo, but after all the dust has settled, I don't really see any change.
Oddly, while I was swollen after the third series, I thought I saw a significant decrease in my bend (like a 25% reduction), but as things healed, the decrease seemed to go away and I seem to be back to where I was when this all started.
I guess at this point, I'd have to hope I'm in the placebo group - like everybody else, I won't really know until study is done, which for me would be sometime in August. Like everyone else, I'm looking forward to seeing what overall results the study gets, and hope they are positive, but would caution that the anecdotal evidence that's coming out might not be completely reliable, unless you're hearing it directly from a study participant. Guess we all have to hang in there and see what comes out of this, in a few months.
G.
Where do they inject you at? The base of the penis? Halfway up the shaft? How far in does the needle go?
Comebackid
Correct me if I am wrong but I would assume they must inject the plaque wherever that is located.
Hawk's about right - the injections are into the plaque.
I do have a few additional opinions and comments about the methodology, but feel bound not to discuss in any detail while the study is in progress - will just have to wait for a while.
G.
MUSICMAN - Your Mar 25 comment below said "25 per cent" improvement. Vernon's comment actually referred to a "25 degree" improvement. That puts a much different (and better) light on the results. Using the 45 degree bend you both mentioned, that results in a 20 degree bend which is over a 50% improvement. Although a 25 degree improvement will only be 100% for those with a 25 degree (or less) bend, I think that would be a welcome improvement to everyone else.
Humorous
G,
I ask about the injection site because it appears I have plaque surrounding my entire penis like a cast. I can't tell what sections or parts aren't fibrotic or not cause no doctors will do an ultra sound on me. I wonder how they would treat someone who did have fibrotic tissue spider webbed throughout the entire tunica. Meaning, whether they would focus on injecting at one specific site or scatter light injections all over (ouch!) :o
Comebackid
Quote from: ComeBacKid on March 27, 2009, 01:28:17 AM
G,
I ask about the injection site because it appears I have plaque surrounding my entire penis like a cast. I can't tell what sections or parts aren't fibrotic or not cause no doctors will do an ultra sound on me. I wonder how they would treat someone who did have fibrotic tissue spider webbed throughout the entire tunica. Meaning, whether they would focus on injecting at one specific site or scatter light injections all over (ouch!) :o
Comebackid
Maybe they would make a judgement based on the curve of the penis? I' not sure that it'd be feasible to inject all over the penis. That said, it will likely depend on the results of these trials.
I was injected in the plaque at the base of my penis. While that is where the largest mass of plaque exists, it is not the only plaque. If I'm understanding this correctly, I have plaque running up a good part of the length of my penis on the top side. I also have an hour glass deformity above the injections site.
I have a sense that the procedure for injection will probably change when they proceed into the next phase of the study. Remember that this is an effectiveness study (& safety). I would think that once effectiveness can be demonstrated then appropriate treatment procedures will be fully developed.
Just following up on what McNally said, I was also injected in just one spot, where I had the biggest plaque (about halfway up the shaft, in my case). I also have plaque along more of the length of the shaft, but they appear to be focusing on the single biggest plaque. My guess is that it might be helpful to inject into more than one location, but I guess that will have to wait until the next study.
G.
I think that when you have a widely distributed lesion, that this injection is going to be harder to place correctly, and less likely to help.
Tim
Gotta go to the government trials for anti tgf beta and get involved in trials for the help you need. Of course that means that you will have to spend as much time writing doctors and labs as you do complaining here.
You will get nothing but sympathy here. Sympathy ain't gon stop peyronies. Spend your time where it can make a difference.
http://clinicaltrials.gov/ct2/show/NCT00812838?term=erectile&rank=183
...This link mentions that they're conducting studies on Botox for the abatement of Peyronies Disease. It was my assumption (perhaps incorrectly) that Botox was supposed to make tissue firmer - i.e. removing wrinkles by tightening the skin - but isn't that the opposite of what we're trying to achieve? I don't know how cavalier I'd be in injecting a neurotoxin into my junk, either. Dead-end or viable treatment?
Given that contractile "machinery" of the cell leads to a contraction of scar tissue, it makes some sense that botox might help lead to that happening less. The mechanics of action is not clear to me, though, as botox should be adherent to the acetylcholine receptor at the neuromuscular junction (or anywhere that acetylcholine acts). I didn't think that it acted at the level of fibroblasts contracting.
Tim
Ocelot, Botox is of course the toxin of botulism. It paralyzes the nerves that contracts muscles. That is why botulism patients often have to be on a ventilator for months after the disease is gone. So it does not tighten muscles up but relaxes them. Like Tim, I can see SOME sense in theory but it seems like a long haul from there to controlling the Peyronies Disease process. Plus it is not the kind of substance or the area of the body that one would want to play around with.
I don't remember seeing a discussion of superoxide dismutases before, but the wiki on Peyronie's disease links to a European study:
http://www.europeanurology.com/article/S0302-2838(05)00256-3/abstract
Now we all know how those wacky European studies can be (but was it done in ITALY? :>). Is there something to this? I'd say any powerful antioxidant would be welcome, but the study says it was an administered gel? I'm dubious that the chemicals could pass through the skin into the TA.
What do you all think?
Ocelot,
Good find. The idea of the study uses liposomes which DO cross cell barriers (though I am not so sure they wouldn't get carried away by blood flow to the skin after absorption). At least there is a rationale for why it might work.
Tim
After some quick searching it looked like this 2005 report was from a Japanese study. After more searching it appears it was a multi-national study. One problem is that there was a total of 30 patients divided into at least 2 groups. Fifteen patients makes for pretty dubious results. http://www.urotoday.com/3351/browse_categories/peyronies_disease. For instance, the improvement of curvature in 23% would be about 3 patients. Improvement was 5 to 30 degrees. One could possibly argue if 2 patients improved 5 degrees then only one had improvement, especially if the measurement was patient reported and not objective. How much of a curve did they have to start with ??? A 5 degree improvement in a man with a 90 degree bend in interesting but not very helpful.
/liposomal_recombinant_human_superoxide_dismutase_shows_promise_in_treatment_for_peyronies_disease.html
These things are difficult to explain short of study bias or hellish coincidence. It would be interesting to see more than the abstract in order to see the method of delivery, study design, and what objective measurements were used.
Quote from: Hawk on March 11, 2009, 03:26:40 PM
In fact stem cell research has never stopped in the U.S. This has been an emotional issue in which both sides often tune out facts and take an emotional ride. There is much research on stem cells that have nothing to do with embryonic stem cells. In fact advances have made it clear that non-embryonic stem cells have shown value that was thought only to apply to those from embryos. These advances have reduced the importance of embryonic stem cell lines.
Furthermore, embryonic stem cell research continued uninterrupted. The restriction was only on newly generated lines of embryonic stem cells. Research on existing lines has been ongoing
Correct the stem cell research has never "technically" stopped, just the government funding stopped, which had the intended consequence of putting much embrionic stem cell research on hold for the term of the republican administration.
Democrats began government funding again and the government is the largest money source for stem cell research. FYI, Geron, ticker (GERN) have the most pattents for stem cell research. Sadly none yet for peyronies, believe me, I wrote them and asked.
Guys,
Found this pilot study for collagenase injections to treat keloid scars. Sadly, treatment of such scars with collagenase was rendered ineffective. Apparently, scar volume reduction, if any, seems to be temporary according to this study.
http://cat.inist.fr/?aModele=afficheN&cpsidt=17872085
Any thoughts?
Also, Auxilium stock fell recently due to concerns that injections may cause a "hypersensitive" reaction...?
Hello folks... This is a blog of one woman's experience with Dupuytren's Disease and Xiaflex. She had great results. She has video links of her experience on YouTube as well. The link is in the body of the text of this link.
http://samanthahoffman.blogspot.com/2008/09/ever-heard-of-dupuytrens-disease.html
I have heard concerns on this page of the rumored rate of success for Xiaflex being low for Peyronie's. Let's keep in mind that the doctors are targeting the one plaque at the center of the bend and doing very static, very uniformed injections into the site. The rate to determine success is 25% improvement in this study I believe. Studies are designed to get the drug passed by the FDA. They walk a fine line at the pharmaceutical companies of keeping the bar low enough to show success and keeping the bar high enough so they can market the product effectively after they get FDA approval.
It is my belief, that after Xiaflex is on the market, experienced Urologists that understand the disposition of Peyronie's will be able to more effectively inject the enzyme into the plaque for enhanced results.
The key to these FDA studies is uniformity and a result that can be measured.
I hope this is helpful and encouraging.
Ted - Very informative. This has made me feel a little more hopeful aboout the prospects of Xiaflex.
Is there a way we can reconcile the study I provided several posts below with this new information? I'm a bit puzzled ???
Believer, I think you are trying to compare apples and oranges here. Dupuytren's and Keloids are two very different things. This is also a reminder that we are NOT just dealing with overaccumulation of collagen here. There has to be something underneath that is driving that phenomenon. Simply eliminating collagen won't help, whether it is by a fastidious diet and supplement regimen OR by injections. The body will just find a way to replace the collagen you remove. On the other hand if the process was temporary and no longer ongoing, then removing the collagen by injection should be effective and I think that is what you are seeing with the reported case. BUT, not every individual will respond the same way, since some may be experiencing ongoing collagen accumulation. - George
I would like to receive personal messages from guys in the Xiaflex trial as to
your results. I will reply as to mine. Most guys don't want to post on forum
this information.
Hello all. I am 29 and new to this site, but have been living with Peyronie's Disease for over a year now. I broke my penis on the rim of a toilet bowl and I'm pretty sure that's how this started. I noticed right away, pain with my erections, indentations, and much loss of rigidity. I went to the doctor after this and he injected something in me to give me an erection to see what I was dealing with. I have since noticed that where he injected me I feel another lump in my penis. And now over a year later, things seem to be getting even worse. I went through three condoms the other night while with a girl trying maintain a very rigid erection while putting them on. It just wasn't happening though. At my young age, I feel very desperate. So, I'm just trying to understand, is this new drug, Xiaflex, suppose to just get rid of curvature, or will it actually turn scar tissue into regular healthy tissue again, getting rid of my indentations. Also, is there anything I should be doing now, to try to maintain what I have, so that it at least doesn't get worse? And lastly, I'm trying to find a GOOD doctor, who is most experienced in treating this. I am in the NJ/NY area. Does anyone know of one? Thank you for listening. Looking forward to any and all of your responses.
bummedout,
I'm about your age (28) and have had Peyronie's for about 2 years. It started out as a small indentation and spread over the course of months until I had a pretty good bend, but has been stable for the past year. I am in the Xiaflex study, but I believe I am getting the placebo since I've seen no improvement.
Before beginning the study I had the idea that the drug melted away the Peyronie's plaque. At the beginning of the study the doctor explained to me that the drug softens up the plaque to allow it to stretch. He may have been dumbing down the explanation for me though. Whatever the mechanism, it is supposed to reduce the curvature.
As far as what to do I would recommend you eat and live healthy, and taking some of the supplements in talked about in the "Oral Treatments" thread couldn't hurt. I currently take Fish Oil, Vitamin E, Acetyl-L-Carnitine and L-Arginine every day. The L-Arginine specifically is cheap and helps make the erections stronger. You'll also see that a lot of guys here recommend Pentox (need a uro to prescribe) and the VED. I haven't tried that yet but it will be my next plan of attack. Sorry to veer off topic - read the Child Boards for a synopsis of all the posts here.
Good Luck
Joe
Thanks Joe, I'll look into the supplements you recommend.
Just as a heads up for everyone, there has been what I consider to be a major breakthrough with stem cell therapy. The researchers are now making progress against Multiple Sclerosis with it. And if it works for multiple sclerosis, that should make it a prime candidate to treat Peyronie's. This whole science is moving quickly now and this will spell renewed hope for a lot of younger guys. I have always considered stem cell stuff to be years into the future, but this breakthrough causes me to reassess that position. I would not be surprised at this point if stem cell therapy became common within the next five years at the rate things seem to be going. - George
Stem Cell Study (http://www.healthfinder.gov/news/newsstory.aspx?docid=626366)
Bummed out,
Check out the "Child Boards" - starting there will give you a running start on knowing what the verious threaads here are about.
Tim
The "child boards"...
https://www.peyroniesforum.net/index.php/board,18.0.html
Quote from: George999 on April 26, 2009, 09:54:25 PM
Just as a heads up for everyone, there has been what I consider to be a major breakthrough with stem cell therapy.
Very promising George! For all of the negatives, we do live in a time where so much progress is being made in so many areas relating to health, and we should be thankful for that.
The study on the stem cell MS research seems very vague, more of a journalism article than a medical one. It also states that the study group was three people? This seems to be a decade off for any applicable purpose, but still pretty interesting/hopeful!
Its really a large scale CASE study, not a full scale research project. Its more like the approach taken by Dr Lue with Pentox. This is what I find attractive about it. Its fairly simple, and seemingly it just works. And the guys behind it are UC docs like Dr Lue.
Tim *might* be able to dig up more on it as he has more resources than most of the rest of us do. However far away it might be for the rest of us, it demonstrates that the cure is already very likely there for multiple sclerosis and application of this treatment is likely going to happen in the not too distant future giving the persuasive abilities of the MS advocacy. And when it becomes available for MS patients, or perhaps even before, other researchers will attempt to apply it to other auto-immune associated syndromes and who knows how many cures will be unraveled in the process. I see it as one of these really big smoking guns that lets us know that the cures are 'out there' for all of our diseases. Its just a matter of time before they are unveiled.
I read through this stuff on a daily basis. That is one reason why I, even in my 60's and with multiple potentially serious health issues, find it difficult to become depressed. You follow this stuff and you observe how fast it is moving along and you just get fascinated! So I am determined to hang in there with the Pentox and the other stuff we know works to get me to the newer, fast approaching, more effective treatments that are on the way. - George
I've learned how to read these breakthrough announcements. Wherever you see "additional studies", translate it as "15 years". If you see "promising", just read it as "needs a billion dollar investment". :)
I like to reflect on the fact that we may be the last generation of humans who have to deal with some of these serious health problems. Diseases like MS, Parkinson's, and Alzheimer's are objects of intense research and the knots are starting to unravel. They won't be curable in our lifetimes, but future generations will not even remember them. Solutions are probably decades away at most.
Things are changing and I think that a couple hundred years from today, our lives in 2009 will appear pretty harsh and grim, especially towards the end. Maybe that also gives us some amount of dignity and character that future generations won't have. We have to accept our fates and go out with our chins up. It will be the same for people in the future - but the problems, and the time scale of their lives, will be different.
j - mate that is so so depressing
j, I think you are entirely too negative. Where we are now as compared to a few years ago is mind boggling. Five years ago or so, my only treatment would be Vitamin E, period. There would be no Pentox, ALC, Vitamin D, VED or all these other things we are finding to be helpful. And there would be no Peyronie's Forum or resource center. Just the same as with MS. MS patients now have a lot of helpful therapies in comparison to just a few years ago and some of them are quite easy to access. Vitamin D for example (High Doses of Vitamin D Cut MS Relapses (http://www.webmd.com/multiple-sclerosis/news/20090428/high-doses-vitamin-d-cut-ms-relapses)). And new USEFUL studies like this one are appearing almost daily. Knowledge is increasing at an exponential rate these days. The whole bio chemistry surrounding Vitamin D and cancer is being unveiled. Now we know, for example, that cancers secrete enzymes that break down Vitamin D and thus disable its ability to destroy them. Now the search is on for a drug that will knock out those enzymes. We are in the final stretch in terms of solving these disease syndromes. Peyronie's as well will benefit dramatically from these breakthroughs, albeit tangentially. Too write off major new treatments in our lifetime is not realistic at all. - George
The FDA has accepted the license application for use of Xiaflex in treatment of dupuytrens. They have given it priority review status. Action is expected by FDA by August 28, 2009.
J,
I agree with george, I think you are entirely to negative. Decades for stem cell cures and cures for major diseases and disorders? I don't think that far, lets see where we are at in one decade from now, just ten years down the road. They are making great progress. Pentox has been a huge gain for us, it that helps and works, just stay on it for a long time, until they come up with a cure. I see it more as a drug to keep you from progressing and small improvments until a cure comes a long. I plan to stay on it for as long as possible. I stocked up ahead of time with 6 prescriptions, and store it in a huge pill jar. If my doctor eventually tires to pull my prescription I'll have at least a year of it, I'd get more than this, but its only good for a year from the date you get it. I keep telling people to get on this cause it is helping me again for the second time. My erections are full and solid, and my penis is hung and full when flaccid, it feels healthier and is softer, but still gets hard when semi erect, and feels damaged. I don't think it will cure you, but it will keep you functioning, and keep you at bay with small improvements. Xiaflex study is moving a long, and could be on the market within a year.
Are you on pentox? Did you try it?
Now that they overturned the stem cell funding, your going to see more money pour in for treatment research and more results. You have to stay patient though, I've been waiting for a cure for a decade now, it could be another 5 years to a decade for me...
Comebackid
I first heard about injectable collagenase in '97 when I read a paper about successful trials at SUNY in 96. As Mark501 posted, Xiaflex is now, possibly, set for FDA approval by the end of 2009. That's 13 years. All the other possible treatments you guys are mentioning - Pentox, ALC, vitamin D - were already approved by the FDA long ago.
"15 years", by the way, is what my hand surgeon told me when I had Dupuytren's surgery in '97 and I showed him that paper about the SUNY trial. He said even if it works, that's how long it would take to get to market.
That was my point - development and approval of a new drug therapy, in this country, now takes many years and huge sums of money. And of course this process only begins after all the research that developed the treatment. Even if a new drug is created in a lab this week that can roll back Alzheimer's, it would probably be too late for most of the people who have it today. If an existing drug were found to work, that's another story.
My post wasn't intended to be as gloomy as the responses are indicating. I don't think Parkinson's, for example, will be cured in my lifetime. Peyronie's, though, may very well be quite treatable in a few years. Maybe just a couple of years.
Realism isn't pessimism.
I think "J" is right about the time frame. Xiaflex might get FDA approval by the end of this year for Dupuytrens. You might look long and hard to find a doctor to use it off label for peyronie's, and it won't be cheap. Xiaflex will not start phase III trials for peyronie's until the middle of 2010 and who knows how long for FDA approval. My condition with this disease is not of inconvenience but of not being able to have sex at all. I am not 23 years old and at my age I don't think I will see these things come to pass. Some of this attitude of mine is the mental anguish of dealing with this disease.
i'm sitting in my urologists office right now. just got my 3rd injection of marcaine, xylocaine and now again marcaine. stupid sh@t wont block me very well and when he tried the xiaflex ..worst pain ever.
i have enough local anesthestic to set off the sensor at the airport when i fly home tonight.
i try and kid about this but , damn...this disease is tough.
cant have the surgery until the study is completed...which for me will be octobre ( say it like you were spanish).
im going to start posting more here...need some place to rant...
oh...my curve got worse by 5 degrees...and my doc thought i got the drug by the response i had locally.
another oh...im a hand surgeon...not sure if i want to see another vial of xiaflex agin ( say like you were a cowboy)
J,
I agree with you about realism, but lets face it they just opened up a flood of federal dollars for stem cell research(which by the way never stopped in the usa and was always going on anyway), many more dollars are going to go to scientists who said they had their hands tied with no funding. Although on the other hand what you say about collaganese is true, it took awhile, but there was no private sector company willing to take it up. Thats why its important to get the info out there about this disease. Theres thousands of men all across the world that have this problem but have no internet connection and no health care to see a doctor. It is more common than you think.
Since collaganese has been seriously taken up by a serious company, it has moved along fairly quickly, what 2-3 years now? Thats not that bad or inefficient, the FDA has to do these studies, and we shouldn't denegrate them even if slows the process down. After all would you want to go in for a xiaflex shot that wasn't tested and have it destroy the inside of your penis? August of 2009, wow thats sooner than I even though, this is something to cheer in my opinion, I'd be camped out to sign up at the local doctors office. I'd put my phone on auto dial and just keep ringing until someone picked up!!!! And in the meantime I'd keep stockpiling pentox and keep taking three pills a day!!!!!!
Comebackid
Comebackkid - It certainly is encouraging that Xiaflex "may" be available at some point in the near future. Depending on your definition of near. Is there anything that can conclusively draw from the Xiaflex peyronies trial so far though? Has it truly been a success? Most of those taking part appear to have improved by 25% of more, which of course is certainly better than nothing. Are the actual results available though, so that we can pick through them? I suppose that's unlikely at this time.
That post about xiaflex is the news I needed to make the rest of my week actually enjoyable :)
Quote from: richB on April 29, 2009, 10:21:22 PM
That post about xiaflex is the news I needed to make the rest of my week actually enjoyable :)
Yes, it is definitely promising to see new treatments potentially being made available to us in the near future. Especially for those recently diagnosed, there will at least now be more options on the table for them. That's half the battle I think really. It helps focus the mind to recognise that there are different approaches and strategies out there, even if none of them are perfect. It makes it seem even more antiquated that some people are still told "here's some vitamin E, now on your way...".
It's the idea that progress is being made that makes me keep up hope. I am confident something will come up that is pretty effective by the time I reach my 30's, which is a long time, but it's better than nothing. I feel like the Vit E thing is based on the fact that most urologists are pretty uneducated about this condition.
newguy
Do not be to quick to dismiss vitamin e. It is an old treatment that worked well for many of us "Old Timers" to Peyronies. The first 12 - 18 months are crucial and vitamin e is easily acquired.
Jackp
Quote from: jackp on April 29, 2009, 11:11:06 PM
newguy
Do not be to quick to dismiss vitamin e. It is an old treatment that worked well for many of us "Old Timers" to Peyronies. The first 12 - 18 months are crucial and vitamin e is easily acquired.
Jackp
Sorry if my comment came out wrong. I didn't mean that it's an ineffective treatment (in fact I myself take it), but rather that those urologists not keeping up with developments sometimes avoid mentioning any other potentially helpful treatments unless prompted to research, or worse still point blank deny that some treatments are of use when we know that they can be (VED etc).
Quote from: ComeBacKid on April 29, 2009, 10:03:50 PMAugust of 2009, wow thats sooner than I even though, this is something to cheer in my opinion, I'd be camped out to sign up at the local doctors office. I'd put my phone on auto dial and just keep ringing until someone picked up!!!! And in the meantime I'd keep stockpiling pentox and keep taking three pills a day!!!!!!
For Dupuytren's not Peyronie's. Though maybe you were actually implying that.
I agree that J may not always be a bowl full of sunshine but he has been around a long time. He is savvy and rational. His time tables are realistic. Keep in mind that something widely available in 15 years IS the next generation for many of us.
Also remember (I forget that many of you were not even born) that in the 50's, mainstream medical science projected a cure for cancer within 10 years. In 2009 (50+ years later) the cure for metastatic cancer (cancer that has spread) is barely higher than it was in the 50's. Most of the improvement are in prolonging life or stopping some early stage cancer with early diagnosis.
We will soon see the fruits of things planted (researched) 15 years ago. Fifteen years from now we will see the fruits of current new research.
Money thrown at the problem today will result in exciting new articles within 2 years that will be treatments in 15 years. That is just how it works. Plus, money to throw at anything is pretty scarce.
PS: George you mention the VED. We gave that to the medical community that resisted it for years. In fact they scoffed at the idea and many still do. We gave that to them, they did not give it to us so that is not a valid example of medical breakthroughs.
Good News - Auxilium Pharmaceuticals will be up for approval by the FDA on Aug. 29,2009. If they get approval they plan on going forward with the product within 60 days after. The product was developed to cure a hand problem but is also thought to be effective with Peyronies and other concerns.Check Auxilium's Press Releases for full story.
I can't wait to try the product!
Quote from: Hawk on April 30, 2009, 03:18:19 PMPS: George you mention the VED. We gave that to the medical community that resisted it for years. In fact they scoffed at the idea and many still do. We gave that to them, they did not give it to us so that is not a valid example of medical breakthroughs.
And who knows what all else we might be able to give to them in the future. Some of the things being looked at these days are very accessible to the point that if they don't pursue, we might well be able to. I am really NOT intending to credit the medical community for all of the good things we have today. Much of that progress is due to availability of the Internet and other modern miracles. - George
I feel like the VED will be a crucial part in treatment when successful injections are created. It's not like D. contractures where the physician can stretch the hand out. It's the only thing that can successfully stretch the tissue in a practical manner, also stretching things uniformly, which is also a benefit.
RichB,
Your right, it gives a solid uniform stretch, this is why I'm a big fan. The fastsize stretcher doesn't give the uniform stretch like the VED, and you can pump the blood into ever little knook and cranny! It will most likely be a part of any future treatment, however it doesn't give a great length stretch, fastsize does this well, perhaps both will be used, who knows?
Comebackid
Quote from: sandy1 on April 30, 2009, 09:39:19 PM
Good News - Auxilium Pharmaceuticals will be up for approval by the FDA on Aug. 29,2009. If they get approval they plan on going forward with the product within 60 days after. The product was developed to cure a hand problem but is also thought to be effective with Peyronies and other concerns.Check Auxilium's Press Releases for full story.
I can't wait to try the product!
Even though it becomes FDA approved doesn't mean that doctors will start to use it. The experts will probably continue to use their present practice of Verapamil until some study shows that Xiaflex is better. I'm anxiously waiting the results of the Xiaflex trial.
Once apprpved, I personally don't think it will be all that long before doctors offer it as an option, and for a price, even if there are some unknowns.
Isn't the point that by the time the FDA approves it the xiaflex studies will be complete and out there for examination? I mean how long are they going to do the studies and not publish anything? At some point people will start critiquing the product and the motives if there are no studies....
Comebackid
Remember, the FDA approves medications for specific uses. In order to gain approval for other use(s) requires additional studie(s). But, of course, these additional studies don't have to start from scratch. They simply get grafted in to the previous approval process at the appropriate level. But more studies are still required for approval for new uses. Otherwise, you are left with the whole off-label thing like you have with Pentox. I would hope that Xiaflex would be approved for Peyronie's before it goes off patent so we can avoid that, because once it goes off patent, you can forget any more FDA approved uses. - George
Do you think treatments such as Perfinidone, Collagenase, and Alagebrium will see the light of day as useful drugs in the treatment of peyronie's?
The alagebrium website appears to be state that studies are still ongoing: http://www.alteon.com/therapeutics/alagebrium though the wikipedia page appears to be more downbeat about the prospects (though, anyone can edit that I guess). Are there any movements or further studies relating to Collagenase and Perfinidone?
All three of those are currently somewhere in the trials process. Whether and where they will emerge is anybodies guess. Of course collogenase in the form of Xiaflex looks promising for Peyronie's. Perfinidone looks promising for Peyronie's BUT there are going to be questions regarding its long term safety for years to come which will likely rule it out for Peyronie's use, this, not to mention its prohibitive cost. Alagebrium, also promising. faces questions in terms of its owner's financial viability and capability to get it on the market for some use in order to produce income. - George
George - Xiaflex is certainly of interest at this point and feels like it's almost within our grasp... well compared to the other possible future treatments. In retrospect I wish there had been a seperate thread for it, because it's quite difficult at times to get a rounded view of how the treatment is going for people and a flow of conversation (tho I appreciate that there is a search button, and know that there is no easy way of dealing with this matter due to the forum structure - it's only a small point anyway :)). Xiaflex appears to have received mixed reviews from those here, so it'll be good to see results filtering through.
Alagebrium is perhaps the most intriguiging one of the three drugs I mentioned, and it's very unfortunate that there are funding issues. The wikipedia page is quite interesting and informative concerning the history of Alagebrium: http://en.wikipedia.org/wiki/Alagebrium
George - when the patients sued the makers of Pirfenidone, they forced the company to make it available to them for life and death cases. Couldn't that precedent be set for Algaebrium? It's supposed to cleave crosslinks formed in diabetics - isn't this a sound diabetic treatment? I know it's very cheap to make and easy to copy, hence not a large profit motive in it, but is it possible that legal intervention can take place to make them provide it to the public? It's not surprising, but still horrible, that something that seems so beneficial to so many with diseases far worse than ours can't be helped by a drug...because it's TOO easy to make and mass produce!
Quote from: ocelot556 on May 04, 2009, 06:11:23 PM
George - when the patients sued the makers of Pirfenidone, they forced the company to make it available to them for life and death cases.
Yup, because they already had study data in their hands illustrating its effectiveness.
Quote from: ocelot556 on May 04, 2009, 06:11:23 PM
Couldn't that precedent be set for Algaebrium? It's supposed to cleave crosslinks formed in diabetics - isn't this a sound diabetic treatment?
If there were conclusive study data to demonstrate that. I'm not sure there is at this point. THAT is the problem.
Quote from: ocelot556 on May 04, 2009, 06:11:23 PM
I know it's very cheap to make and easy to copy, hence not a large profit motive in it, but is it possible that legal intervention can take place to make them provide it to the public?
Legal action against WHO? The FDA? They are the roadblock at this point. I'm sure Synvista would be happy to be able to market it. They would have to pressure the FDA enough to get them to allow it.
Quote from: ocelot556 on May 04, 2009, 06:11:23 PM
It's not surprising, but still horrible, that something that seems so beneficial to so many with diseases far worse than ours can't be helped by a drug...because it's TOO easy to make and mass produce!
Its sort of the same problem as what we face with Pentox except that Pentox IS approved for other uses. Just about everybody who has ever used Alagebrium is reporting benefits, but that is not enough to win FDA approval. They want studies which cost $$$$$$$$$$$$$$$. Where is all that money going to come from? - George
Would it be possible, or easier, for them to get approval in a different territory without requiring such large amounts of funding? Also, did their trials start up again, since they terminated from at the end of January? http://www.reuters.com/article/pressRelease/idUS240508+28-Jan-2009+PRN20090128 It's quite frustrating, as Alagebrium itself seems to be cheap to produce. Still, I guess we should be heartened that such discocveries have even been made and may eventually benefit millions.
Its worse than that. There are a lot of therapies known to hold great promise that are likely to never see the light of day due to the fact that nobody can make any money off of them. Things happen not because they can benefit mankind, but the prime mover is only that they can make someone money. This is a reflection of a broken system, since it should be the role of government to identify things which can greatly benefit society and fund those things with public money in the public interest. But that whole approach is not in vogue these days. If it can be privately developed its toast. - George
George999 - You'd think that in these circumstances, another country would take the lead by offering the streamlined approval process, so that at least it was available in many other countries, and effectively could be distributed worldwide. I suppose money is still a factor though, as if something is cheap to produce, there will likely not be much of a profit margin in it for then, and other companies elsewhere (india etc) will produce generic versions which would cut into their profits yet further.
Quote from: newguy on May 04, 2009, 05:28:52 PM
Alagebrium is perhaps the most intriguiging one of the three drugs I mentioned, and it's very unfortunate that there are funding issues.
There is a nice summary of alt-711 research at this site (http://morelife.org/researchems/ALT-711.html). In a study of diabetic rats (PMID 16490017 (http://pubmed.gov/16490017)):
QuoteRESULTS: Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels.
I've been taking generic alagebrium since January of this year. While I don't have ED, I saw a benefit in terms of a better erection after just 2-3 days taking about 80 mg/day. I perhaps haven't been taking it as regularly as I should have, as I take it on average one out of two days a week.
While the anti-ED effects really stand out, I have unfortunately not seen much in the way of a big anti-Peyronies Disease benefit. I may up my dose to 70 mg twice daily for a while to see how that goes.
s&s
You can acquire generic versions of the drug? If that's the case, I'm surprised it hasn't been mentioned here before.
An interesting post about Alagebrium, or rather AGE Breakers Beyond Alagebrium : http://agebreaker.72pines.com/2007/05/14/age-breakers-beyond-alagebrium/
From this it appears that Alagebrium breaks down one particular type of AGE (diketone crosslinks), when in fact there are several. As such the effectiveness of Alagebrium likely depends on the type of injury/complaint, because different crosslinks are likely involved depending on issue at hand. It seems that glucosepane may be the most common AGE compound in humans, and Alagebrium doesn't break this down. A number of companies are working on discovering a glucosepane AGE break though.
Don't take this to mean that alt-711 is ineffective, but rather that it doesn't alter certain types of crosslinks and in future there will likely be a more rounded and effective approach to dealing with them.
EDIT: Also, I had no idea that aspirin may also inhibit the formation of pathological A.G.E. crosslinks. Of course, that doesn't help where existing crosslinks are present, but it's useful too know. On a cautionary note, I wouldn't advise people to take an excessive number of bloodthinners (vitamine e, aspirin etc), especially if they use, or intend to use the VED.
QuoteAustralian scientists say they have developed a drug with the potential to save millions of lives from kidney disease.
The scientists from the University of Melbourne, St Vincent's Hospital and Bio21 Institute say the drug may prevent a condition responsible for up to 45% of all deaths in the western world, mark an end to dialysis for patients with kidney disease and reduce the need for organ transplants.
The team say the breakthrough drug FT-11 works by preventing the spread of fibrosis, the irreversible scarring of vital organs, which is the underlying killer in illnesses such as kidney disease, diabetes, heart failure and lung and liver problems.
Currently there is no available treatment which prevents or halts the spread of the condition and the race is on to produce an antifibrotic drug.
In preliminary trials on rats FT-11 had a 100% success rate with no side effects and human trials on 30 patients are expected to begin soon.
Professor Darren Kelly who has led the two-year research project, says it could save the lives of millions of patients around the world and bring an end to kidney dialysis and also offer an improved lifestyle.
Dr. Kelly says FT-11 has the potential to be a block buster drug with enormous financial rewards; Melbourne University shares patent rights for the drug through Fibrotech Therapeutics.
The plans are for the drug to be initially developed to treat kidney disease caused by diabetes and could mean the difference between taking one tablet a day as against needing eight hours of dialysis every few days; the drug could also be used to prevent diabetes.
Kidney Health Australia, says fibrosis causes the majority of chronic kidney diseases and any drug that could stop the onset of scarring to the kidney would be a major advance. There are currently 10,000 Australians on dialysis.
According to Professor Kelly if clinical trials are successful the drug could be available within eight to 10 years.
- www.news-medical.net/?id=40755
Another possibly useful drug some way down the line. Who is to know whether it will be effective in trials, but it's another example of the progress taking place in this area.
newguy: Thanks for sharing this report. It is very hopeful...once again, it shows how so many things are connected and that we are not in this alone.
JackieO
Quote from: Jackieo on May 06, 2009, 01:26:49 AM
newguy: Thanks for sharing this report. It is very hopeful...once again, it shows how so many things are connected and that we are not in this alone.
JackieO
Yes, that's right Jackieo. I know that guarenteed solutions are not available for us at this time, but there is a great deal of research taking place because there are massive implications (and money to be made) for effective treatments in these areas. Also, it's easy to sometimes think "what are people doing for us" when really, so many people are suffering conditions that are actually life threatening. They are living day to day praying that these drugs will emerge, and however intensely horrible our own situations are or may become, at least most of us do not have concerns on that scale. It can be difficult to count blessings when we are involved in such a struggle, but sometimes I do manage to do so, and I think it's a healthy mindset to achieve.
Sigh...
Still seems like it would be easier to stop eating refined carbohydrates in excess, to stop the ravages of diabetes.
Tim
http://www.nytimes.com/2002/07/07/magazine/what-if-it-s-all-been-a-big-fat-lie.html
In addition to all of this, we currently have a political leadership in this country that is VERY serious about channeling more $$$$ to research. This is the first time in a long time that this has been the case. That is a VERY good sign. Previous administrations have given lip service to research, but have created public policy that has hindered it. The last president to vigorously support research was JFK and that effort got us to the moon and beyond and brought a number of key medical advances in the process. Over that period and in its wake a number of 'untreatable' medical conditions became literally curable. I am thinking especially of cardiac issues. - George
Are there many people out there taking part in the xiaflex trials who have experienced reduced curvature? A few have got back to us, but it'd be nice to get some updates from those taking part, or from those lurking on the site..
Should xiaflex ultimately not prove to be very useful for peyronie's, what do we propose would be the reason for this? I'm not trying to be unduly negative, simply thinking of all of the eventualities.
Quote from: George999 on May 06, 2009, 11:08:36 AM
In addition to all of this, we currently have a political leadership in this country that is VERY serious about channeling more $$$$ to research. This is the first time in a long time that this has been the case.
That sounds like a statement from someone that has bought into political rhetoric and not looked at the actual ledger. This is not the time or the topic for a protracted debate but it is my opinion that you could not be more wrong if you think medical research will be better funded in the next 4 years.
Quote from: Tim468 on May 06, 2009, 10:11:14 AM
Sigh...
Still seems like it would be easier to stop eating refined carbohydrates in excess, to stop the ravages of diabetes.
Tim
http://www.nytimes.com/2002/07/07/magazine/what-if-it-s-all-been-a-big-fat-lie.html
Tim,
I share your sigh. People that like to attack carbs make no distinction between refined and complex carbs. My son has lost 100 lbs in the past year eating complex carbs & protein with very low fat intake. He is "ripped" with very low body fat and clear muscle definition. He obviously exercises.
my personal experience has been that the carb quantity matters more than the type of carb. thats been the case with my diabetic sister at least. I also have had great success with a low carb high fat moderate protein diet. Of course the word low would vary from one person to another. I also think saturated fat gets a very bad name.
Gary Taubes, who wrote the seminal book (though many folks don't know it yet!) called "Good Calories, Bad Calories" eviscerates the AMA, ADA, AHA and supporting governmental bodies for their low fat dietary recommendations that emerged from the McGovern report on nutrition in 1977. There was overwheling data to support the "alternative hypothesis" that carbs were the proximate cause of obesity and most health problems related to "Westernization", but the cardiologists recommending dietary change didn't know that literature (or believe it if they knew it).
Since then two things have happened. First, primarily through the emergence of high fructose corn syrup, Americans have added 30 pounds of simple sugars to their annual diet in the forms of glucose, sucrose (which is a 50/50mix of fructose and glucose), and "high fructose" (~55/45 split) corn syrup - overwhelmingly the latter.
But in addition to the addition of 30 pounds of sugar (taking us to an average of 150 pounds per capita per year!!!), the annual intake of grains has increased by 60 pounds per person per year.
The effect of the low fat dietary recommendations has been to shift our intake over to to less fat, and by definition, higher carbs. "Low fat yogurt", Cheerios... you name it - all in the name of a "heart healthy diet". But sugar or high fructose corn syrup remain high on the lists of ingredients for all these items.
And with a change in the makeup of the diet, came an increase in the amount of calories taken in (approx 400 calories more per day). So, yes, more in means more stored, but the laws of thermodynamics are not simple and did not apply as is often stated (that "a calorie is a calorie is a calorie").
Instead, insulin secreted when we eat carbs causes the avid uptake of triglycerides into fat (not just the shunting of glucose into muscle cells). We are left in a chronic state of hunger, as much dietary fat is removed from circulation and stored, and we have higher cravings of hunger.
So rather than sloth, gluttony or other moral judgements about obesity, we could see it as a disorder in fat metabolism. We could see less activity as the result of the altered metabolism, and not the cause of the increased weight gain. We could see the increase in appetite and not due to bad character, or flaws exploited by evil empires of corporate bad guys conspiring us to eat their food (though they do exist!) - rather, we could see the weight gains as due to a large change in our national eating patterns that were unparalleled in history - ever. And the primary driver of that is carbohydrate intake - simple and more "complex".
When we eat whole grains, we get more micro-nutrients - it is not the same as having them added back in the form of "enriched" flour. But the process of milling and refining flour, although it allows us the food to survive longer as it is more resistant to rotting, promotes faster absorption of calories and the release of insulin. Again, insulin is the primary driver of fat storage and carbs in any form are the primary driver for insulin release.
So, complex carbs that are slowly absorbed simply cause less insulin surges, and the micronutrients are better for you. The absolute amount of carbs is also far lower. What used to be called the low carb density foods (some are better for you than others) include Kale (5%) versus potatoes (40%+).
So "complex carbs" that include fresh fruit and leafy green vegetables are different than carbs that include grains, grain products and sugars. I think the "iffy" zone is in the whole grains. These are better for you than refined white flour due to better nutrient value, but may still give you the hit in insulin that one needs to avoid. Even when looking at fruit, it helps to compare the density of carbs to weight of the food.
Hell, even putting anything sweet in your mouth causes an immediate release of insulin, which may account for the fact that folks drinking diet pop still tend to gain weight over time.
Tim
Here is the link again:
http://www.nytimes.com/2002/07/07/magazine/what-if-it-s-all-been-a-big-fat-lie.html?sec=health&pagewanted=print
Tim, I certainly agree with that assessment. Many people succeed with diets that cut fat to the bone or cut carbs mercilessly or other radical diets BUT that success seldom lasts. In the end, hunger asserts itself and things can go downhill fast. Instead we need to understand that ALL these nutrients are necessary INCLUDING a reasonable amount of GOOD fats. On the other hand, all these nutrients exist in toxic forms which we need to avoid. A lack of understanding about the foods we are eating is devastating our health. A lot of people also are taking to "juicing" for health and weight loss. This article (http://www.healthday.com/Article.asp?AID=624866) indicates how that trend is ruining people's teeth among other potentially negative impacts. The reality is that a lot of foods sold under the cover of being healthy are actually among the worst offenders. - George
I firmly believe thats if its pure fat loss and retention of muscle mass you're looking for, a full keto diet works best. Of course you have to be principled enough to follow such a diet and there are many variations of the diet that make it doable and manageable. The problem with a Low fat, low calorie high carb diet is that while you do lose a significant amount of weight you also drop a lot of muscle mass.
I also believe that the biggest problem is AGE. As far as whole grains are concerned, I think the concern is with phytic acid.
I agree with most of the recent statements. I have all but cut refined carbs out of my diet. I used to eat sweets (candy to my american friends :)) quite often, but I can't remember the last time I did in recent times. I avoid anything excessively sweet really (including sweeteners) and whenever I literally have to eat something sugary (like cake at a birthday party) it tastes insanely sweet to me. I eat lots of fruit and veggies though, but typically the actual fruit rather than drinking juice. I feel that juice it's likely to cause a spike due than eating actual pieces of fruit. Also, it's very easy with fruit smoothies to drink a whole carton, then realise than you've guzzled down a hampers worth of fruit and 100g+ of sugar in about five minutes: http://www.innocentdrinks.co.uk/things_we_make/smoothies/carton_black_rasp_boysen/ I think you CAN have too much of a good thing :).
I've been following the reports of dietary research since the 70s and I think I finally understand what the experts are telling us.
Fat is bad - no wait, fat is good. Sugar is bad, it's always been bad, except it used to be bad just because it was empty calories - now we know that glycation is aging our brains, so no sugar. Dark chocolate is good, it's full of antioxidants. But where do I get chocolate without sugar? Carbohydrates are good - no, today only complex carbohydrates are good. Um, but wait, they contain sugar so maybe not so good. Fruit is definitely good. Fruit is a health food! But fruit also has too much sugar. So "an apple a day" is out. Except we have to have fiber, and apples have fiber - wait, I think the link between high fiber and reduced colon cancer has just been discredited. So I guess fruit is out? But it has vitamin C which prevents cancer - or used to, I don't think it does anymore.. Red meat is bad, we all know that from way back. Oops, not anymore - now protein is good. So lean meat is good and fatty meat is bad? No I think the latest is that the fat is good, too. The Innuit live on blubber! Fish is very good. Unless it came from the ocean, or a lake, or a river - then it probably contains too much mercury. Fish oil is good if you can get it without the mercury. Cholesterol is very bad, it clogs your arteries. Well actually today only bad cholesterol is bad, and good cholesterol is good. But don't they come from the same place? I forget...
Broccoli was good in the 70s and is still good today, although the reasons are different. Broccoli is a survivor, a winner, like if you'd bought a share of Berkshire Hathaway way back when. But it's not good for breakfast.
Smoking is bad. I'm quite sure about that.
Quote from: j on May 10, 2009, 03:07:46 PM
Smoking is bad. I'm quite sure about that.
....but what if we smoke Broccoli ???
Exercise is good. Antioxidants are good. So we exercise and take antioxidants, right? Ha.
http://www.nytimes.com/2009/05/12/health/research/12exer.html?_r=1&em
It's like the investment advice we get from money gurus via TV and magazines. One thing is certain: whatever we did with our money last year was exactly the wrong thing. As for what we should do now, well that's a little tougher - we're supposed to carefully examine our personal financial goals and consider a range of investment options... based on our own tolerance for risk...
Here is some new info on Xiaflex, that you need to interpret how you see fit, but tallies with what some of the posters on this forum have been suggesting
http://industry.bnet.com/pharma/10002040/pfizers-penis-straightening-drug-may-cause-swelling-redness-and-bruising/
Either way we have about 4-6 months to wait for the high level results from the Phase IIb study, if they are reporting in the 4th quarter.
In my opinion the guy who wrote that article is just a bonehead with no real understanding of what he's writing about.
Swelling and redness are no surprise - this enzyme is literally dissolving tissue, it's an active process, not a magic wand. If you read the actual quotes from the Auxilium people, they aren't concerned. The article contains other misinformation too - Dupuytren's disease does not "deform the hands into claws", that's just plain silly.
I'll bet he's shorted the stock.
j - Not sure what to make of the vitamin + exercise study. Personally, at this time I still think that the benefits of exercise, a healthy diet and supplements is the way to go, and outweight any possible negatives.
UK - I don't think the articles emphasis on "swelling, redness and bruising" is very professional. The conference call as good as states that any injections into the penis can cause this type of reaction, so it seems as it the bnet article is looking for an alarmist angle. It's all about weighing up the options anyway. Maybe in some individuals injecting anything will actually make their condition worse, but if the results of the trials are, on the whole, positive and show that xiaflex does benefit most people, then it makes it a viable option. Of course, right now the jury is out on whether it will prove to be viable, but if it is, then in combination with healthy living, supplements, pentox, and so on, hopefully we're in a better position than most to maximise the pros and limit the cons.
I find the anti-oxidant study a bit disturbing. The whole thing about the body using free radicals as markers is novel, but quite likely real. If that is indeed the case, then we just might be doing the body a disservice by preempting it with antioxidants and making it somewhat blind to problems. Certainly as a result of this news, I will be scaling back on anti-oxidant use. This comes right on the heels of research tying certain B Vitamins, including folic acid, which has been highly promoted, with increased incidence of cancer. So, in both cases, perhaps we ending up fixing one thing and screwing up something else. I think the real solution here lies in the development of blood panels to access deficiencies and allow the patient to correct them without having to use a blind shotgun approach where the nutrient that is being supplemented the heaviest is actually the one that the patient has an excess of and the deficient ones end up not repleted at all or not sufficiently. - George
Quote from: George999 on May 12, 2009, 08:01:53 PM
I find the anti-oxidant study a bit disturbing. The whole thing about the body using free radicals as markers is novel, but quite likely real. If that is indeed the case, then we just might be doing the body a disservice by preempting it with antioxidants and making it somewhat blind to problems. Certainly as a result of this news, I will be scaling back on anti-oxidant use. This comes right on the heels of research tying certain B Vitamins, including folic acid, which has been highly promoted, with increased incidence of cancer. So, in both cases, perhaps we ending up fixing one thing and screwing up something else. I think the real solution here lies in the development of blood panels to access deficiencies and allow the patient to correct them without having to use a blind shotgun approach where the nutrient that is being supplemented the heaviest is actually the one that the patient has an excess of and the deficient ones end up not repleted at all or not sufficiently. - George
That's the ideal. Even without that, I think the average person would benefit from keeping a close eye on their diet for a period of time, then seeing what is missing and what isn't in terms of nutrients. for instance, in hindsight my Vitamin D intake was pitifully low. Maybe in time it will be revealed that megadoses of any vitamin really cause more harm than good. Supplements should supplement, rather than provide the basis for healthy living or patch up a bad diet. This study hasn't really worried me iun relation to anything I take, other than possibly vitamin E, which I do take reasonably high doses of. I'll stick with it for the time being, and see if future studies reveal similiar findings.
I found the original article online and it is a dense and tough read - not sure about their conclusions yet.
Tim
Tim. I think that what we are discovering about folic acid is really instructive. WITHOUT supplementation we know that we will see increased incidences of birth defects and such. WITH supplementation, we know that we are seeing increased incidence of certain kinds of cancer. This would indicate that rather than comparing supplementation with non-supplementation, we need routine annual serum folic acid measurements on a broad group of people. We THEN need to be comparing birth defects and cancer rates and we need to determine optimum folic acid levels. We will likely find that only a small subset need to be supplementing, for many others it will be optional, and for some others, any supplementing at all will be risky. And I think that this strategy will likely apply to other key supplements as well. Nutritionists have been criticized for doing this sort of stuff for years. But there application of it has been questionable, since they have not really identified optimal blood levels via long term well controlled studies. BUT, their concept has been a good one. As it is now, a few people are suffering because of a deficiency of [ fill in the blank] ... so we tell everybody to start supplementing with it. Wrong! (and not very scientific) - George
http://www.reuters.com/article/pressRelease/idUS240508+28-Jan-2009+PRN20090128
Well, it looks like the almighty dollar has set algaebrium back another ten years. So much for progress... I'm losing hope that anything will ever be developed for our condition!
Xiaflex was on, off, on again for years as the money ran out and new funds had to be raised. If alagaebrium has real value, someone else will buy the rights and restart the trials.
we are all doomed - nothing good about this - very very very DISMAL
Quote from: Iceman on May 21, 2009, 01:02:10 AM
we are all doomed - nothing good about this - very very very DISMAL
No, but Synvista may be. I'm not up to speed with this potential drug, but I did notice a few things about the press realease.
First, it's dated January 28, 2009, almost six months ago.
Second, that press release contained a dire forecast about it's potential implosion:
"The Company is continuing to explore strategic alternatives in order to monetize its technology assets, which may take the form of sales or licensing transactions with respect to those assets. In light of the Company's cash position and current negative economic and capital markets conditions, if the Company is unable to enter into such transactions in a timely manner,
the Company's ability to continue operations beyond the second quarter of 2009 is in doubt."
You hate to have to put that in a financial disclosure.
Finally, the company decided to delist from the NY Stock Exchange last February and it's currently trading for $00.13 per share on the OTC.
Sorry in advance if my observations are old news, but the press release is old new.
CF
Quote from: Iceman on May 21, 2009, 01:02:10 AM
we are all doomed - nothing good about this - very very very DISMAL
Sorry to disagree Iceman. I agree that the whole issue with Alagaebrium is disappointing. But I have seen very few positive comments from the Xiaflex trials. I know many in the trials have purposely not been posting, but you would think that if there was a good percentage of those seeing improvement that we would have heard about it somehow. I think at best this may have been another thing to try that may have worked for some and not for others. There was no indication that this was the all mighty cure. No different than a Verapamil alternative in my opinion.
And to say we are all doomed I assume is more of a figure of speech. Many have seen improvement from the current forms of treatments including traction, VED usage, Verapamil, drugs like Pentoxifylinne, supplements, and yes..... even surgery. I think the worse thing we can do for new forum members is to give any indication that "there is no hope" and "nothing can be done". Sort of like the message I hear from some uninformed urologists. ;)
I agree with the below comment. We have a responsibility to think carefully about what we write here. I wouldn't want new members to find this site and feel even worse than before they arrived here!
We are NOT doomed, far from it. The reality is that Alagebrium is available. At least one person on this forum has been using it. Trials will not make it work any better or any worse. IF it proves helpful, more of us will likely gain access to it. BUT, and this is a big but, viewing Alagebrium (or anything else) as the final cure is part of the problem. NOTHING on the horizon today is the "final cure", BUT there are a lot of things that can be helpful. Auto immune syndromes all tend to wax and wane in some pattern. We get better and feel upbeat, then we suffer a setback and feel depressed. We have got to break this cycle. We have got to learn how to use things like Pentox to temper the setbacks. We have got to find more things like Pentox to temper the setbacks, and most of all, we have got to learn to temper our psychological responses to the setbacks. Why? Because the REALITY is that people who are positive and optimistic in the face of adversity do considerably better physically than those who crumble under trial. So look at the bigger picture. Be thankful for the good times and be willing to fight like a tiger through the bad times and not throw in the towel. We WILL be doomed IF we doom ourselves by being defeatist about this. - George
Thanks George999, Newguy, and lwillisjr...
and, hopefully my particular post was to point out that it sounds like the termination of the trials was based on the overall economic health of the company and not the effectiveness of Alagebrium.
Financially, it looks like the company is dealing with serious cash flow problems and is having to make some difficult choices in the short term to be able to survive.
A couple of weeks before the announcement back on 1/28/2009 the company released encouraging news about Alagebrium:
http://phx.corporate-ir.net/phoenix.zhtml?c=100218&p=irol-newsArticle&ID=1243189&highlight=
CF
ive complete my series and about to return to my urologist for the measurements...
More angle. Decreased size.
Anyone else want to comment?
Quote from: bones54 on May 21, 2009, 11:49:16 AM
ive complete my series and about to return to my urologist for the measurements...
More angle. Decreased size.
Anyone else want to comment?
Was your size and curvature entirely stable prior to the xiafles injections?
With injections there is always a concern in my mind that there is at least the potential to do more harm than good. Of course, it depends what's being injected, if it's proven etc. It's all about playing the averages and the more information is available the better the choices we are able to make. Unfortunately the jury is still out of Xiaflex at present. From your other posts it does seem that you experienced more bruising and pain than would perhaps be expected.
I really do hope that this is just a temporary setback and that over the coming months you see improvements. If not, it might be worth trying the VED and/or light traction and taking pentox.
I can't see how one can put a good spin on the alagebrium report, despite what some optimists might be saying.
Even if the drug is purchased by another company, Two Phases of studies have been washed down the drain. That's approximately two years added on to any chance of seeing this drug on the market while they repeat these studies, and that's if the rights were bought and study goals were submitted today. Not to mention that there's the much longer Phase III trial that alagebrium never got to see. It doesn't matter if this drug cures Peyronie's with the first pill - if it doesn't go through the arduous years of testing, the FDA won't let us have it. It works with the same efficacy as it did when it was discovered in the '80s, but that doesn't do us any good if we can't get it!
Part of me thinks that this company was conducting these tests more as a dog and pony show, since they bought the corporate shell for Alteon to sell a different drug. WHY a company would abandon a drug that has the best possibility of any contemporary drug in the field to help REVERSE AGING, I don't know. Peyronies Disease aside, something that would ameliorate wrinkles and diabetic vascular damage... it has $$$ written all over it, yet it seems like it can't get anywhere...
As this has happened before with Synvista, as per the wiki article, and the fact that the drug itself has been around since the 80's...yeah. I'm not willing to say we're doomed, but for those of us who were hoping AGE breakers were the answer... we've got to find other answers. And I don't frankly buy that a member of this forum is taking the drug - where are they getting it? Why have they not posted results, or HOW exactly they're acquiring this drug which can't legally be sold? I'd be a guinea pig if I knew where to acquire it, by legal means or otherwise.
EDIT: I will add, however, that after some reading apparently the AGEs that alagebrium was supposed to break were apparently much more important in the rat model that the human model. We glycate differently, I guess, so those promising rat studies just weren't backed up in the human model, though there was apparently efficacy vis a vie changes in the heart chambers in humans. So while I agree it never was a "cure", the fact that a potential therapy has dried up in a time where there are virtually NO therapies being tested for our malady... it doesn't lend itself to giving hope to those of us praying for science to swoop in and save the day.
Quote from: ocelot556 on May 21, 2009, 03:41:55 PMIt doesn't matter if this drug cures Peyronie's with the first pill - if it doesn't go through the arduous years of testing, the FDA won't let us have it. It works with the same efficacy as it did when it was discovered in the '80s, but that doesn't do us any good if we can't get it!
This is a misunderstanding of the role of the FDA. There are plenty of "substances" on the market that are not approved by the FDA. Alagebrium was around for a long time before it was picked up by Synvista's predecessor to potentially market as a drug. It is a generic substance that has been tested this way and that way over the years. The FDA ONLY prohibits the sale of generic "substances" when they 1) are being marketed as a drug or 2) have been shown to be a hazard to health. Otherwise, no huge problem. The real question is whether or not it will be picked up by a reputable vendor. If not, you really have no guarantee as to the quality of what you are getting and that can be a problem.
Quote from: ocelot556 on May 21, 2009, 03:41:55 PMI'm not willing to say we're doomed, but for those of us who were hoping AGE breakers were the answer... we've got to find other answers.
Just don't forget that Alagebrium is only the first and most primitive AGE breaker. Other companies are doing research in this field and are already doing initial testing on other even better AGE breaker candidates. Alagebrium was really the proof of concept in this whole chase. It is already in danger of being made obsolete by newer more promising candidates.
Quote from: ocelot556 on May 21, 2009, 03:41:55 PMAnd I don't frankly buy that a member of this forum is taking the drug - where are they getting it? Why have they not posted results, or HOW exactly they're acquiring this drug which can't legally be sold? I'd be a guinea pig if I knew where to acquire it, by legal means or otherwise.
Well, why don't you PM them and ask them where they are getting it? People on this forum are getting Pentox without prescription. Its not rocket science. I myself have seen it marketed, I just didn't trust the vendors, thats all. Its out there and available, I can pretty much guarantee that. So here is at least one member that is taking Alagebrium, you can PM them and find out the scoop: Forum Post (https://www.peyroniesforum.net/index.php/topic,36.msg19672.html#msg19672)
Quote from: ocelot556 on May 21, 2009, 03:41:55 PMSo while I agree it never was a "cure", the fact that a potential therapy has dried up in a time where there are virtually NO therapies being tested for our malady... it doesn't lend itself to giving hope to those of us praying for science to swoop in and save the day.
As I stated above, other AGE breaker candidates with more viable futures are already undergoing preliminary research AND, if you really want Alagebrium, you can most likely get it, legally even. - George
Ok - i was just a bit hasty - i reckon that ive had improvement with ved and pentox - plus phsycologically i really am on top of it - keep up ved and pentox and youll be at least doing positive things
completed the last of the xiaflex 6 weeks ago......flew into chicago last night...caverjet injection..measurement...cabby back to airport...fly back home..parking lot payment...pay the babysitter.....5 hundy all told...
my angle has increased 5 degrees since beginning treatment.
cannot have any surgery until ive completed the last 2 study measurements.
fastsize came in the mail yesterday..not supposed to use it until after the study is done...
are there any out here on the forum who would care to relate their results so far in this study?
also completed Xiaflex trials and my curvature improved 5 degrees. In my opinion, these rather minor degree changes are nothing more than measurement variations and represent no change.
i agree that 5 degrees is within the range of examiner variability...but it somehow feels better to complain a litttle..javascript:void(0);
http://seekingalpha.com/article/135832-auxilium-pharmaceuticals-inc-q1-2009-earnings-call-transcript?source=yahoo&page=1
During this call, Auxilium's CEO talks about, and answers questins about, the status of Xiaflex for Peyronie's and the results of the recent phase IIb trials. It's long and I've only skimmed it, but I noted these points:
1. This was just the IIb trial. The phase III trial wouldn't even start until next year.
2. The amount of improvement that needs to be shown seems to be sort of up to the FDA.
3. From this trial they learned that their injection protocol probably wasn't optimal; it would be more effective if the injections were spread out.
4. They're trying to decide whether 'modeling' (stretching) would improve the results.
5. They're focusing on 'patient reported outcomes', rather than objective measurement of angulation, as success criteria.
6. At this point there's a fair amount of corporate-speak and weasel-wording in response to the question of whether phase IIb was successful.
As I said, I only skimmed it. On the whole I would say it's positive, they're moving forward, and looking at ways to improve the treatment.
QuoteINTRODUCTION: Transforming growth factor-beta1 (TGF-beta1) has been known to play a crucial role in the pathogenesis of Peyronie's disease (Peyronies Disease). AIM: The aim of this paper was to investigate the therapeutic effect of IN-1130, a novel small molecule inhibitor of activin receptor-like kinase (ALK)5, a type I receptor of TGF-beta, in an animal model of Peyronies Disease. METHODS: Peyronies Disease was induced in rats through repeated injections of adenovirus expressing TGF-beta1 (days 0, 3, and 6; 1 x 10(10) particles/0.1 mL, respectively) into the tunica albuginea. The rats were divided into five groups (N = 10 per group): group 1, age-matched controls without treatment; group 2, age-matched controls receiving repeated injections of IN-1130 (days 30 and 37; 5 mg/kg in 0.1 mL saline, respectively); group 3, Peyronies Disease rats without treatment; group 4, Peyronies Disease rats receiving repeated injections of saline (days 30 and 37; 0.1 mL, respectively); group 5, Peyronies Disease rats receiving repeated injections of IN-1130 (days 30 and 37; 5 mg/kg in 0.1 mL saline, respectively) into the lesion. MAIN OUTCOME MEASURES: Penile curvature was evaluated by use of an artificial erection test at day 45, and the penis was then harvested for histologic examination. Collagen in the plaque was quantitatively assessed by hydroxyproline determination. RESULTS: IN-1130 induced significant regression of fibrotic plaque through reduced infiltration of inflammatory cells, reduced transnuclear expression of phospho-Smad2/phospho-Smad3, reduced hydroxyproline content, and reduced cartilage content and restoration of elastin fibers in the fibrotic plaque of Peyronies Disease rats, which was accompanied by the correction of penile curvature. CONCLUSION: Antagonizing TGF-beta signaling through the use of ALK5 inhibitors may represent an exciting new therapeutic strategy for the future treatment of Peyronies Disease.
- http://www.ncbi.nlm.nih.gov/pubmed/19473283?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
It's not being used in humans yet, but is surely potentially promising for early stage peyronies. My core concern with all of these injectables in animal studies (which may not respond the same ways in humans anyway), is that during studies it's impossible to take into account any inherent suseptability to developing these conditions. It may be the case that injectables designed to treat these conditions are rather unfortunately least effective in people suffering from peyronies because these are the very same people who may have an exaggerated response to any damage done to the penis. That said if it can be shown that more good is done than harm that's all that matters.
I'm not as hopeful about Xiaflex as I once was because we're heard mixed coments, but maybe if they adjust the injection schedule and add traction is will me more effective. I'm jumping the gun a bit I suppose. When are we due to next hear from the company?
When reading negative reports on Xiaflex and Alagebrium, one has to remember that both of these have been funded on a shoe string and are quite honestly only proof of concept treatments. In both cases there are far more advanced variants in the pipeline along with new approaches as pointed out by newguy in the previous post. We are still a long way off from a quick fix, but vastly improved treatments are on the way. - George
George999, I don't completely agree with your assessment of Xiaflex.
It has now been shown to work quite well for Dupuytren's contracture and is well beyond the proof of concept stage - it should be in wide use for Dupuytren's within a couple of years at most.
For the last few years, Auxilium seems to have funded it adequately (before that it's another story).
With Peyronie's, results so far are marginal, but "proof of concept" is a bit harsh I think. They need to refine their treatment protocol considerably, but the "concept" seems pretty solid.
J, I fully agree that the concept is solid. By "proof of concept", I mean just that, that Xiaflex has proven the concept viable. And following Xiaflex, I believe we will see more and better treatments that follow the same approach. I am not negative at all about Xiaflex. But I try to be realistic in its capabilities. I believe they will be shown to be limited and we will still need multiple treatment modalities to control Peyronie's, and note I use the term control as opposed to cure which I believe we will not see in the near future although we will likely come close. - George
A question that puzzles me often is that most, if not all, of these treatments are for people in the early stages. If this is true, then why even bother looking at any of these treatments if you've had the condition for longer than a year or two? Not trying to be negative, it's just a thought.
RichB - I see there as being various stages for positive intervention by treatment:
1) Immediately following injury to the penis (if the person is aware that an injury has taken place) (Oral meds - esp Vit D, Pentox, NSAIDS - possibly surgery if a fracture occured during intercourse)
2) In the weeks/months/(years) that pain and plague is present/developing/resolving (oral and mechanical aids - traction, ved - maybe verapamil injections)
3) If/When the condition has stabilised (oral treatments, but possibly emphasis on mechanical aids)
3 continued) Following a bout of peyronies (assuming that it does stabalise somewhat), a maintenance stage of oral (various) and mechanical (VED, traction) treatments can be used to attempt to simultaneously aid the current condition, and help ensure that the body is better able to deal with any reoccurences of inflammation and/or fibrosis which may come about due to new injury (as many of us are likely more susceptible to these inflammatory cascades than most of the male population).
In this system, I see the use of xiaflex as being a stage 3 treatment and as such it can potentially be of use to guys long after their peyronies has occured, as long as their condiiton hasn't calcified. Assuming that it does become a recognised treatment for peyronie's its use could possibly be significantly enhanced by those simultaneously taking various oral medications and using techniques which stretch the penis in some way and impede inflammation and fibrosis.
As for why to concentrate on treatments that may or may not be suitable for any particular person, I think that comes down to the community aspect. We all know how horrible it can be to suffer from this condition, so it an early stage treatment emerges which is useful, it's in a sense our responsibility to hightlight it and let people know that it could be the right treatment for them.
Quote from: RichB on June 15, 2009, 12:13:22 AM
A question that puzzles me often is that most, if not all, of these treatments are for people in the early stages. If this is true, then why even bother looking at any of these treatments if you've had the condition for longer than a year or two? Not trying to be negative, it's just a thought.
RichB,
Good point. Peyronies can be very different in it's symptoms and the way that it attacks each of us. So we need to be careful about suggesting or recommending the same treatments and time for everyone. For some who have Peyronies and deal primarily with pain, then they could go for years on oral meds for example to help keep the pain under control. For others, there is documented accounts of being able to keep the plaque in check with periodic flare ups. Again prolonged use of oral meds and VED/traction techniques may help and provide a reasonable remedy.
And then there are those like myself who definitely had plaque and in my case was causing an extreme deformity. A sharp curve of 70 degrees. I progressed through the classic textbook phases of initial stages, acute development, and then stabilization. And after 18 months the plaque was beginning to calcify. For people in this situation I agree that I don't see that continued usage of oral meds or therapies would do any good. I had already tried most of these and nothing helped.
The curve was acute, intercourse almost impossible (at least painful for my wife), and traditional approaches didn't help. I think men in this situation have got to face the fact that they must evaluate the risks of surgery at this point. I don't see any other cure coming in the near term. Some are waiting for the results of Xiaflex but I don't think it will be any better than Verapamil. It may work for some but won't be the silver bullet that helps everyone.
So we get to the point of "do we live with what we have been dealt with?", or do we evaluate the risks of surgery. Each must make their own decisions.
I think Xiaflex will eventually be much more effective than Verapamil. In fact I don't think verapamil works at all, despite claims to the contrary. My guess is that Xiaflex injections will be combined with agressive "remodeling" - i.e. stretching - and that this treatment will make a big difference for a lot of guys. If you have an acute, localized bend that might actually be a good indication for Xiaflex therapy because it presents a well-defined target.
Lwillisjr:
I don't think that calcification makes surgery a necessity. In this day and age, pentox has a good chance of staving off that process and there are always other medications coming down the pike. A quick search even uncovered drug trials being conducted today that are effective in reversing muscle calcification!
http://www.ingentaconnect.com/content/bsc/apl/2006/00000009/00000003/art00021
"Abstract:
A 25-year-old female patient with documented diagnosis of polymyositis developed extensive muscle calcification in the left thigh muscles with overlying skin induration one year after her disease onset, despite well controlled myositis. Plain X-ray of the left femur and hip revealed extensive calcification involving the periarticular soft tissue shadows around the left hip and left upper thigh. The patient received diltiazem 90 mg/day in divided doses and follow-up plain X-ray study after 6 months of treatment revealed almost complete resolution of the muscle calcifications."
As we wait for a medical drug cure time is passing us by. Xiaflex for Dupuytrens Contracture was in phase II in 2002 and they are hoping for FDA approval close to the end of this year. Xiaflex for Peyronie's will not start a trial in phase III until mid 2010. How long to get FDA approval for Peyronie's is up to your guess. If approved for Dupuytrens a person might find a doctor to use it off label, but I think it would be very pricey .
If you are a young man time is on your side. If your curve is slight you can still function. If your condition arrived at the average of 50 to 60 years of age and your bend is extreme then as I said time is running out.
I have been told "so what if you can not have sex, there is more to life than that! Easy to say to a man that can not walk as you run by him.
It seems to me like drugs that improve blood flow are crucial to preventing any kind of fibrosis. Has that drug been used to treat peyronie's patients before?
Here, I did a quick google search and came up with this. I have never seen this posted before: http://www.freepatentsonline.com/y2001/0047037.html
In section C:
"[0113] Whatever the mechanism, the present medicament shows an astonishing efficacy, particularly considering the miserable failure of such closely related prior attempts at Peyronie's disease treatment. One patient involved in experimental evaluation of the present medicament exhibited a penile curvature in excess of 75 degrees—a condition which was both painful and which effectively rendered the individual completely sexually dysfunctional. After using the medicament of the present invention, in the prescribed manner, this patient's Peyronie's disease symptoms were completely reversed in two week's time. Other experimental patients, albeit with less severe symptoms, have shown equally remarkable and complete recoveries, including one patient who suffered from Peyronie's disease for over sixty years, never having previously experienced success with any prior treatment regimen undertaken by numerous physicians."
What? This is, as I can see, just topical verapamil. It is dated from 1999.
RichB - That's the problem with so many studies. They don't appear to pertain to reality.
Quote from: ocelot556 on June 16, 2009, 02:37:33 PM
Lwillisjr:
I don't think that calcification makes surgery a necessity. In this day and age, pentox has a good chance of staving off that process and there are always other medications coming down the pike. A quick search even uncovered drug trials being conducted today that are effective in reversing muscle calcification!
Ocelot,
You are making the assumption that muscle calcification and plaque calcification are the same. And maybe they are. I'm not trying to be negative. But there are guys that have been waiting for years for "The Cure". And if you have calcified Peyronies plaque and don't have a severe bend, then maybe hoping for a near term cure is OK. My only point is that for those who have severe bends resulting in nearly imposible sex, and calcified plaque, you had better give surgery a hard consideration.
I can state for a fact a direct quote from Dr. Levine. He is the one that told me directly that once calcification sets in, that surgery is the last option available today.
RichB, Jerry Easterling's "topical" verapamil treatement has, in my opinion, been thorougly descredited several times over.
Talked about in the past I know, but a few new studies here:
29th April 2009
Quote1. Pirfenidone (PFD; 5-methyl-1-phenyl-2(1H)-pyridone) is an effective and novel agent with anti-fibrotic and anti-inflammatory properties. We investigated the anti-fibrotic effects of PFD on experimental liver fibrosis models in rodents, and its possible molecular mechanisms. 2. Liver fibrosis was induced by carbon tetrachloride (CCl(4)) in Balb/c mice. PFD (250 mg/kg) and silymarin (50 mg/kg) were given to different groups by gastric gavage for 4 weeks. PFD significantly attenuated fibrosis severity by 49.8% and 44.9%, respectively, measured through histopathological scores and hydroxyproline levels in liver tissue. Its anti-fibrotic effects were significantly higher than in silymarin-treated groups. 3. Liver fibrosis was induced by albumin antigen-antibody complex in Wistar rats, and the same dose of PFD and silymarin were given for 8 weeks. PFD significantly reduced fibrosis degree by 45.0% and 51.0%. Its anti-fibrotic effects were comparable with silymarin-treated group. 4. Effects of PFD on expression of extracellular matrix (ECM)-associated genes in human hepatic stellate cells (LX-2 cell line) were measured by real-time quantitative PCR. It significantly inhibited expression of smooth muscle alpha-actin (alpha-SMA) and type-I collagen in activated LX-2 cells in a dose-dependent manner. 5. PFD was effective in ameliorating fibrogenesis induced by CCl(4) in mice and by albumin-complex in rats. This was mainly mediated through its anti-activation and anti-fibrogenesis effects on hepatic stellate cells.
- http://www.ncbi.nlm.nih.gov/pubmed/19413596?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
March 5 2009
QuotePurpose: To investigate the role of pirfenidone, a novel antifibrotic agent, on proliferation, migration, and collagen contraction of human Tenon's fibroblasts (HTFs). Methods: After treatment of HTFs with pirfenidone, cell proliferation was measured by MTT assay. Cell migration was investigated by Scratch assay. Contractility was evaluated in fibroblast-populated collagen gels. Cell viability was determined by trypan blue exclusion assay. The expressions of TGF-beta1, -beta2, and -beta3 were estimated with RT-PCR, Western blot, and immunofluorescence analyses. Results: Pirfenidone induced significant inhibitions of HTFs proliferation, migration, and collagen contraction in a dose-dependent manner. After treatment with different concentrations of pirfenidone (0.15, 0.3, and 1mg/ml) for 24 and 72 hours, cell viability showed no difference between treatment and control groups. After 24 hours of treatment with pirfenidone, HTFs showed decreased mRNA and protein levels of TGF-beta1, -beta2, and -beta3 with a dose-dependent manner. Conclusions: These findings indicate that pirfenidone inhibits proliferation, migration and collagen contraction of HTFs at nontoxic concentrations. Decrease in autocrine TGF-betas signaling may have roles in the effects of pirfenidone.
- http://www.ncbi.nlm.nih.gov/pubmed/19264889?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
QuoteScienceDaily (May 17, 2009) — A large, well-controlled, multi-national clinical trial program has demonstrated the effectiveness and safety of what may become the first FDA-approved medicine for idiopathic pulmonary fibrosis, or IPF.
In a Phase III clinical study program called "CAPACITY," investigators discovered that the oral anti-fibrotic and anti-inflammatory agent, pirfenidone, could slow the deterioration of lung capacity in patients suffering from IPF.
The researchers presented their findings on Sunday, May 17, at the American Thoracic Society's 105th International Conference in San Diego.
The CAPACITY trial consisted of two multi-national, randomized, double-blind, placebo-controlled Phase III trials (CAPACITY 1 and CAPACITY 2) designed to evaluate the safety and efficacy of pirfenidone in IPF patients with mild to moderate impairment in lung function. The primary endpoint of change in percent predicted forced vital capacity (FVC) at week 72 was met with statistical significance in CAPACITY 2 (p=0.001), along with the secondary endpoints of categorical change in FVC and progression-free survival (PFS), defined as time to either death, a 10-percent decrease in FVC or a 15-percent decrease in DLCO (diffusing capacity of the lung for carbon monoxide). The primary endpoint was not met in CAPACITY 1 (p=0.501), but evidence of a pirfenidone treatment effect on the primary endpoint was observed at several periods in that trial. Importantly, greater than 80 percent of patients in the trials completed treatment and greater than 90 percent completed the study.
An exploratory analysis of pooled data from both trials revealed that treatment with pirfenidone resulted in a 30-percent relative reduction in the percentage of patients who experienced an absolute decline in percent predicted FVC of at least 10 percent. This magnitude of decline is considered clinically meaningful, as a 10-percent decline in percent predicted FVC has been shown in multiple studies to be an independent predictor of mortality in patients with IPF. Exploratory analyses of pooled data from the two CAPACITY studies also demonstrated a statistically significant treatment effect on the primary endpoint of change in percent-predicted FVC at week 72, progression-free survival time and change in six-minute walk test distance.
"While it was disappointing that the primary endpoint was not met in CAPACITY 1, important consistencies between the two CAPACITY studies were observed in the overall treatment effect of pirfenidone," said Paul Noble, M.D., co-chair of the CAPACITY program and professor of medicine and chief of Pulmonary, Allergy and Critical Care Medicine at Duke University Medical Center. "The treatment effect observed in the CAPACITY studies was generally consistent with that observed in the Phase III study in IPF patients conducted by Shionogi in Japan. Collectively, these three studies give us a very good sense of the impact that pirfenidone has on the progression of IPF over at least one year."
According to the National Heart, Lung, and Blood Institute, about 200,000 Americans have idiopathic pulmonary fibrosis, a condition that scars tissue deep in the lungs. Most patients are diagnosed with the disease in their 50s and 60s, and many people live only three to five years after being diagnosed. There are no approved medications in the United States or Europe to treat the disease. Pirfenidone is approved in Japan for the treatment of IPF.
A total of 779 patients were enrolled in the CAPACITY trials at 110 sites in 11 countries. The mean age of participants was 66. To be eligible for the study, patients had to have a definitive diagnosis made by high-resolution CT scan or by biopsy, and a FVC ≥ 50 percent of predicted values and a DLCO ≥ 35 percent of predicted value.
Dr. Roland du Bois, M.D., professor of medicine at National Jewish Health, in Denver, Colo., and CAPACITY co-chair, concurred that these studies were very encouraging for IPF sufferers and added that "the safety and tolerability of pirfenidone was reassuring. The principal side effects experienced by patients in the studies were gastrointestinal discomfort and photo-sensitivity, both of which were manageable in the majority of patients."
The CAPACITY trials follow a Phase III clinical study conducted in Japan that was reported at the American Thoracic Society's 2008 International Conference in Toronto. That trial, which demonstrated the ability of pirfenidone to reduce the decline of lung capacity and improve progression-free survival, served as the basis for the Japanese regulatory authorities' approval of the medicine for the treatment of IPF in Japan.
- http://www.sciencedaily.com/releases/2009/05/090517143231.htm
I suspect that if/when its approved by the FDA, it will be more readily available, and only a matter of time before somebody uses it for peyronies.
The claimed result is "a 30-percent relative reduction in the percentage of patients who experienced an absolute decline in percent predicted FVC of at least 10 percent." Sounds pretty weak.
j - Yes, that did occur to me when I made the last post. It could well be enough case on "works wonderfully in rats, but not well in humans". Still, some improvement is better than none, and used alongside other oral treatments this could potentially amplify its effectiveness. Maybe in those with long term peyronie's (most of us here) it may be of limited effectiveness, but for those new to the condition, maybe it could tip the balance.
lwillis --
Levine is very cutting edge as far as doctors go, but like most doctors related to Peyronies Disease they're not as clued-in to drug studies as we are. Levine for a long time held doubts that the VED would be of use, but after patients sent him photos and reports of progress with the VED, he began a study and became one of the prominent proponents of it's use.
I don't know if muscle and plaque calcification are similar, but Pentox's use was initially for claudication - it just so happens that making the red blood cells more squamous happens to force them into hard-to-reach places like fibrotic plaques better. My uro has me on a topical ointment that counts EDTA as an ingredient. EDTA is a chelating agent, used to remove heavy metals/calcium buildup. Xiaflex aside, medicines aren't being targetted to our condition - so we have to grasp at straws with drugs like Pirfenidone, Trazodone and others, formulated to treat more serious diseases but with the capacity to help ours.
You're absolutely right, however, on the last point. I'm speaking from my own position (many plaques but very slight bend, with ED). If one has a bend that makes sex impossible, I'd concur with yourself and Dr. Levine. But surgery, especially penile prosthesis, is a permanent solution to what in 10-20 years might be a temporary problem. They'll have a cure for Peyronies Disease before they have the ability to successfully attach a new biological penis, or restore what's been done in the Nesbit.
Quote from: ocelot556 on June 17, 2009, 04:32:06 PM
You're absolutely right, however, on the last point. I'm speaking from my own position (many plaques but very slight bend, with ED). If one has a bend that makes sex impossible, I'd concur with yourself and Dr. Levine. But surgery, especially penile prosthesis, is a permanent solution to what in 10-20 years might be a temporary problem. They'll have a cure for Peyronies Disease before they have the ability to successfully attach a new biological penis, or restore what's been done in the Nesbit.
You probably have not lived with peyronies and all the other side effects like many of us.
There is such a thing as quality of life. I have been living with this for almost 15 years. For the last 4 the quality of my sex life was not acceptable. I tried every thing legal, and some not, to improve. At 66 I did not have the option of waiting 10-20 years.
The only way I could get the quality of my sex life back to near normal was a penile prosthesis. Now at 8 months post op I have a better sex life than a lot of 20 year olds.
Surgery is an option of last resort. But when done by doctors like Dr. Milam, Dr. Levine and Dr. Lue that option will make you "normal again"
Jackp
Edited to fix Quote -
Hawk
Sorry if I offended you, jackp, but I don't come to this forum and engage in discussion because I enjoy the company. I have been suffering from peyronies and the side effects for three years now. It's not as long as most here, but I know full well how it affects one's quality of life.
The purpose of my post wasn't to deride anyone who has it worse than I do. I'm happy that some of us have found happiness and functionality with surgery. I was simply suggesting that with the rapid advancement in biotechnology and pharmaceuticals, younger sufferers might do better to live with that reduced quality of life and try to exhaust every non-invasive treatment first, as you did. Obviously age and severity of the disease is a consideration, but we're in total agreement about it being a last resort. When I see drugs in studies that suggest they might help even calcified plaques and all the other things that would otherwise necessitate surgery, that last resort doesn't seem so final.
If I had a necrotic limb, and I cut it off tomorrow, and two days from now they cured gangrene - they still wouldn't have the technology to grow my arm back.
I really believe that surgery is the last option and has to be weighed very carefully by the patient since it is irreversible. HOWEVER, this is an agonizing decision that must be made by the patient with the counsel of his doctor. While we should encourage caution in this regard, we also should understand that each person's situation is different and what is right for one is not necessarily right for another. We should also all be thankful that if surgery is needed, there are docs out there who can do a darn good job at it. So I as much as I am expecting near term breakthroughs with systemic treatments, I am also delighted when guys come back here and report that they got fed up with waiting and opted for a surgical fix and are thrilled with the results. These guys may not have a new penis, but at least now they have a fully functional one and are no longer consigned to the "waiting room" not knowing whether or not the doctor will ever be "in" for them. We need to support both approaches here and provide the best information we can as guys struggle to make these difficult choices. - George
Quote from: ocelot556 on June 17, 2009, 07:56:50 PM
If I had a necrotic limb, and I cut it off tomorrow, and two days from now they cured gangrene - they still wouldn't have the technology to grow my arm back.
You do not have a clue on what a penile prosthesis is. I look normal, feel normal and have normal sex. If you saw me in a locker room you could not tell I have a prosthesis.
All a penile prosthesis does is replace the spongy tissue in the corpora's with chambers that inflate and deflate. Nothing else in the penis is disturbed. If ever the technology you suggest is developed it is easily removed.
Georeg999
I read your post with great interest. If anyone ever finds the "magic bullet" I believe you will be the one. Thanks for the post I agree whole heartily.
Jackp
Edited to fix Quote
Hawk
Interesting discussion. As I read it some advocate waiting for a "cure" even if all current non-evasive treatments have failed. The thought is that the silver bullet is bound to come sooner or LATER and surgery cannot be undone.
All of this is speculation based on:
The hope that the cure will come in this generation
The speculation that surgery will not be able to be undone in this generation.
The concept that someone with successful surgery even wants it to be undone
Disregard for the years of active sex life made available in the meantime with surgery.
I question the legitimacy of any of these arguments much less all of them in one single sweep. If you are wrong an any one of them then surgery is an attractive option after current non-evasive methods fail.
Flipside: What if you wait (unable to have intercourse) for 30 years for the cure that does or does not come, only to realize that with a prosthesis you could have had 30 years of normal intercourse and that tissue regeneration can replace penile tissue if you ever decide you don't prefer the surgical results. All this is very possible since they can CURRENTLY strip all the cavernosal tissue from the penis of a rabbit and regenerate a fully functional organ. Tissue regeneration is not science fiction. The advances are astounding and my guess is it is as likely to be available for human use as quickly as a silver bullet in the form of an oral med. used to cure Peyronies Disease. Clearly I have no way of knowing that but no one has any way of knowing the opposite.
Guys,
I find this discussion fascinating. Is everyone assuming that surgery results in a prosthesis? I we all know that jackp is thrilled with his. And I would have gotten one if necessary. But you need to understand all the surgical options.
I don't want mine undone regardless of what discoveries are made in the next [fill in the blank]. My plaque was removed and simply a graft put in its place. My penis looks normal, feels normal, I get straight erections, and I achieve orgasm through various forms of stimulation and sexual positions.
Did I take a risk to get this? yes, as I felt the odds were in my favor.
WHY WOULD I WANT THIS UNDONE ?!?!?!
I think the point about surgery being irreversible has more to do with failed surgeries. Some surgeries do fail you know. And in the case of a failed surgery, the person can be left in a worse state than where they started from. Are there inherent risks to waiting for a non-surgical cure? Of course! But there are also risks when taking the surgical option. And there are cases when even a second surgery can't fix a surgery gone wrong. And then were back in the same old boat of waiting for new medical technology that may not come in our lifetime, and worse off to boot. ALL of these things have to be considered when making that decision. As with a lot of other aspects of this disease, there is NO slam dunk. - George
Quote from: lwillisjr on June 17, 2009, 10:21:29 PM
WHY WOULD I WANT THIS UNDONE ?!?!?!
Good point. Many peyronies disease sufferers would envy your position (since your surgery was successful). I certainly believe that in some cases surgery is a viable option. It all depends on the individual I guess, weighing up the risks, potential for future improvement and so on.
Wow, I had no idea how much of a nerve I'd hit with some of the posters on this board.
A few things about my argument that are seemingly getting lost in the discussion: I explicitly mentioned younger sufferers. I don't think anyone would tell a 60 year old man to wait for a better treatment, if that treatment wasn't immediately in the pipeline. I also didn't say not to get surgery, I suggested that one take MORE time with non-invasive treatments. We know the study that suggest Pentox works better at month 6 than month 1, better still after years 1 and 2. I'm not saying one should wait 30 years, but is 2 years too long to wait? What's the exact cutoff in years between exhausting the non-surgical options and 'wasting your time hoping for a silver bullet'?
So using the logic that's followed me being told I have no clue, that my ideas are illegitimate AND that I don't have peyronie's or its symptoms -- why don't we ALL stop posting here, stop reading abstracts, lock up our VEDs, stop wasting money on meds and supplements and just go under the knife?
I'll answer for myself. I don't want to lose size with grafting or Nesbit procedures. I'd rather have a Colt .45 that has trouble firing than a Derringer that shoots every time. If it came down to getting a prosthesis, I'm still not sure I'd be able to do it - it might look and feel normal, but it wouldn't seem normal to me. I've read that you can feel it when it's not hard, too, like a weight, and if you get it at a young age you might have to get further surgery to get it replaced in 10-15 years, or to deal with infection.
I'm not trying to scare anyone away from surgery. I don't have a horse in the race. Do with your penis what you will.
Edit note: First post came off a little resentful at people "dissing the poster, not the post", and was too rhetorical.
Ocelot,
My understanding of surgery is that it's not really a good option for those with ED, but really mainly only for those without ED, who just have too great a curve for comfortable sex (I'm talking about the less scary non-prosthesis procedure). If I'm wrong, someone please correct. The second thing is that the smaller the degree of your curvature, the less you lose from Nesbit surgery. I'm in the same situation as you (ED, misfires, very slight curve, young) and personally I'd be thrilled IF there were a relatively safe surgical way I could sacrifice the centimeters necessary to straighten me out AND it completely restored erectile function to the way I used to be. Hell, I'd even sacrifice the same amount in girth if it were possible!
See J and I's report on topical verapamil, in my opinion that product doesnt work and was an utter failure! I can't count the nights I spent letting the gel "sink in" on my penis while it caused extreme itching and irritation on my testicles, inner thighs, and penis as it spread around when I had boxers and clothing on after applying it. I spent a good sum of cash on the junk and it was a waste!
Comebackid
Quote from: ocelot556 on June 18, 2009, 12:21:22 AM
Wow, I had no idea how much of a nerve I'd hit with some of the posters on this board.
Ocelot, I didn't see much to suggest you hit a nerve. I saw that you made some comments that some disagree with or see differently, thus a discussion ensued.
For instance, in your last post you are still assuming loss of size is a major issue. There are several types of surgery. Some reduce size, some do not. Some are actually reported to increase girth. Consider that along with the fact the some guy that starts with 8 1/2 inches may not mind an 8" penis. Someone starting with 4 " may have a different view
IF we are discussing only surgeries that shorten the penis. There simply are no blanket solutions. You have to individualize some of your statements to YOUR specific personal preference for your specific set of circumstances.
Quote from: ocelot556 on June 18, 2009, 12:21:22 AM
Wow, I had no idea how much of a nerve I'd hit with some of the posters on this board.
Ocelot556,
I think it has generated some good discussion. No offense taken. Your points are valid in that trying alternatives for a few years is reasonable. Surgery shouldn't even be considered unless alternatives have been tried. But to me it is not dependent of age. It was just as hard for me at the age of 52 as it would have been at the age of 22.
The bottom line fact is that surgery is scary. The morning of my surgery I was still second guessing myself. Clearly there are those who have been chasing "The Cure' for many more than just a couple of years. I think those of us who have had surgery feel that it is a more viable option than people think. And doesn't even always end up with loss of length. I know 2 guys who had surgery that did not lose any length. It certainly is an option worth evaluating. There just aren't many facts or data regarding surgery (either good or bad) that helps one feel like they are making an informed decision. I do have a copy of a study completed by Dr. Levine. This was a long term follow up of over 200 of his patients who had surgery (both Nesbit and grafting). I'll try to take some time and figure out how to get it posted here.
Quotelwillisjr -I do have a copy of a study completed by Dr. Levine. This was a long term follow up of over 200 of his patients who had surgery (both Nesbit and grafting). I'll try to take some time and figure out how to get it posted here.
That would be enlightening. The attachment limit is 300kb, if the file is too big maybe zipping it will help. If not, then there are always file upload sites such as megaupload.com and rapidshare.com .
What is this???
http://www.curepeyronies.net/
I found this site about a year ago and signed up for their e-mail update list. I recieved an e-mail today that the site had been updated. After reading the information on it...it sounds promising.. Has anyone else heard of this?
Cut and pasted from the website:
Quote"The most discouraging aspect of producing this website is the lack of any significant progress in the effective treatment of Peyronies Disease (Peyronies Disease). This may be about to change with findings published by South Korean researchers in the Journal of Sexual Medicine 2009; 6:1284-1296. In order to adequately discuss this article and its findings, I have to define the following terms.
Transforming Growth Factor (TGF) - one of several proteins secreted by transformed cells that can timulate the growth of normal cells. It is known to be up-regulated in Peyronies Disease and is responsible for the fibrotic scarring that leads to penile curvature. For Peyronies Disease, a decrease in TGF is a positive development because it lead a reversal of the process that results in Peyronies Disease and symptoms such as scarring and penile curvature.
Collagen - is a fibrous protein and its over production results in decreased tissue elasticity. A decrease of this substance is also a positive development.
The South Korean Researchers were studying the effects of a novel transforming growth inhibitor known as IN-1130. Laboratory rats were given repeated injections of TGF in the tunica albuginea section of the penis. Forty-five days after injections, the untreated rats exhibited, scarring, fibrosis, loss of elasticity in the penile tissue and significant curvature. That is, they developed what is known in humans as Peyronies Disease. One group of in the treatment group was given injections of IN-1130 at intervals of 30 and 37 days.
Rats treated with IN-1130 showed a significant, but not complete regression of the fibrotic plaque, which resulted in restoration of elasticity and correction of the penile curvature. The collagen content in the fibrotic plaque was significantly reduced to amounts comparable to the control rats.
Injections of IN-1130 did not significantly affect serum concentrations of pro inflammatory markers. That is, there was no significant allergic response.
The researchers noted that in their opinion this was the first report showing that pharmacolgical intervention was potentially useful in the treatment of Peyronies Disease when given at the early, unstable and progressive stage of the disease.
Further studies are needed to address whether this intervention induces regression of fibrotic plaque and correction of penile curvature if administered at the chronic or stable phase of the disease.
What follows are charts based on the findings from the research paper. Note that I couldn't reproduce some of the data in the charts with the absolute exact values as the researchers, but my values below are very close. For example, I couldn't tell if penile curvature in the control group was 5,6, or 7 degrees. Also, for simplicity sake, I left out some data that were in the original research and printed in the journal article.
In this finding, IN-1130 essentially corrects penile curvature of rats who are in the early stages of Peyronies Disease. Each bar depicts mean values for 6 animals per group. It is interesting to note that those rats with Peyronies who were treated with Saline solution developed an even more severe penile curvature.
IN-1130 reduces transforming growth factor expression. Each bar represents the mean values of 6 animals per group. The values are presented as a percentage of the total number of cells counted. As noted earlier, over expression of TGF is thought to result in Peyronies symptoms and a decrease in the activity ameliorates the symptoms.
Wow! Where does one go to give these guys additional funding. For a man with Peyronies this research article represents a potential breakthrough treatment. (And I emphasize the word potential because the research is in the early stages and has not been tested on humans). These laboratory rats had only two treatments with IN-1130 and had a remarkable improvement. Who knows what would have happened with additional treatment.
Almost one-half of all human medical deaths are somehow related to scar tissue disorders. This ubstance, IN-1130, has been tested on other scar tissue disease and has exhibited healing properties. According to Kidney International, it suppresses renal fibrosis. TGF plays a central role in the progression of renal fibrosis. IN-1130 significantly suppresses this progression. It also may be a breakthrough treatment for prostate cancer. According to the Journal of Urology, Volume 180, Issue 6, IN-1130 demonstrated an enhanced immune response to cancer cells and is a potential prostate cancer treatment.
I am trying to get additional information on this substance. Who owns it? Is it in the public domain for does a private company have a patent on it? Is there additional Peyronies Disease testing planned? Stay tuned."
The guy who runs the site seems to be someone who genuinely cares. I corresponded with him via e-mail when I first discovered the site. Thoughts?
PS: post formatted for quote box, spacing, and line length.
Hawk
thought .....it will amount to zip - see xiaflex for example
From Nature Biotechnology this week:
Pfizer swallows Wyeth, validates niche buster
Cormac Sheridan, Dublin
Introduction
In late January, Pfizer made the headlines with its purchase of Wyeth, of Madison, New Jersey, for $68 billion. Though the merger made the bigger splash, another Pfizer deal, unveiled in December, could have equally substantial repercussions for biotech. The partnering agreement for Xiaflex with Auxilium Pharmaceuticals may be axiomatic of the type of future deal that New York–based Pfizer, and the rest of the pharma field, hopes to ward off pending revenue loss.
With much of large pharma facing near-term patent expirations on key products, the pressure to quickly replace revenues remains intense. And pharma won't be very selective about the areas involved, one analyst noted. "They'll take anything, as long as it wiggles and it works," says Andrew Weiss, an analyst at Zurich-based Vontobel. That will include 'niche busters'—drugs that successfully target limited markets—in the hopes they will fill in the revenue gaps formed by the multibillion-dollar drugs going off patent. (See Box 1 below).
For Pfizer, the deal with Auxilium, of Malvern, Pennsylvania, seems to fit the niche-buster profile, though Xiaflex (clostridial collagenase for injection), a bacterial collagenase, might grow into something more. The deal with New York–based Pfizer, which includes an upfront payment of $75 million as well as regulatory and commercial milestones totaling $410 million, is noteworthy not only because of the niche indications involved but also because of its limited geographical scope. Auxilium retains North American rights to the product, while Pfizer has rights for the European Union plus 19 other European and Eurasian countries. "It might be unique from that perspective," says Eric Schmidt, senior biotech analyst at Cowen & Co. in New York. "Maybe it's a sign that the biotechnology industry has greater leverage over the US pharma industry than it used to. That can't be a bad thing."
Xiaflex, based on a combination of several subtypes of collagenase enzyme derived from the bacterium Clostridium histolyticum, has completed a phase 3 trial in Dupuytren's contracture, and a biologics license application (BLA) filing is expected imminently. It is also undergoing a phase 2b study in Peyronie's disease, with top-line data expected later this year. Each condition arises from a thickening of collagen fibers. Dupuytren's contracture affects the hand, and makes straightening and extending the fingers difficult. Peyronie's disease causes an upward curvature of the erect penis and can result in pain and impaired sexual function. In each condition, surgical rupture of the collagenous tissue has been the only treatment option.
Schmidt says the niches targeted in the alliance simply constitute business as usual. "Biotech has made a living out of taking exotic indications few have heard of in the past and turning them into cash machines," he says. And that's what Auxilium (and now Pfizer) expect to do here: "It looks like about 3% to 6% of the Caucasian population in the US and Europe have some form of Dupuytren's contracture," says Auxilium spokesman Will Sargent. And Auxilium estimates that about 475,000 men visit urologists in the US and Europe every year seeking treatment for Peyronie's disease. "Pfizer did its own market research, and it matched what we had done," he says.
Though Auxilium sees the product as an eventual blockbuster, that is up for debate, of course. Jon LeCroy, analyst at Natixis Bleichroeder in New York, remains unimpressed with the deal, saying that Xiaflex won't move "Pfizer's earnings at all."
But the Wyeth merger would, or at least would add sales. Through the buyout, Pfizer gets Wyeth's stable of approved drugs, though many of those are facing patent expiration, too. It also gets Wyeth's share of the behemoth biologic Enbrel (etanercept), which has no generic competition, as well as vaccines.
Though Pfizer's need to fill a revenue gap is the most acute among its peers—its lucrative Lipitor (atorvastatin) franchise, worth $12.4 billion in 2008, will start to unravel in 2010—plenty of companies are under similar pressure and need to make moves (Box 2). For example, the hypertension treatment drug Diovan (valsartan), marketed by Novartis, of Basel, Switzerland, which achieved $5.7 billion in sales in 2008, loses patent exclusivity in 2011. "They have a pipeline they can work on, but they have to make sure that it works out," says Weiss.
Perhaps there is a different way forward for pharma, beyond the buyouts and traditional licensing. Edward Stuart, cofounder of HS LifeSciences, of Zurich, is managing a new evergreen, early-stage investment fund called QureInvest. HS LifeSciences has developed a distinctive approach to developing companies, in which it actively avoids venture capital investment and seeks early-stage deals for its portfolio firms that will minimize drug development time and maximize patent-protected sales. Some pharmaceutical firms are open to the model, Stuart says, though successful partnering always takes long-term commitment and a sense of realism on both sides of the table. Big pharma companies have to deploy their power intelligently, while biotech needs to relinquish its traditional swagger. The whole industry must take a step back and re-examine.
It could happen. "Everybody is looking at it pragmatically at the moment," Stuart says.
[Box 1]
Niche medicines have had a good track record of late, featuring prominently in the tally of 25 new drugs and biologics that the US Food and Drug Administration approved last year. For example, two thrombopoietin receptor agonists gained approval for treating immune thrombocytopenic purpura: Nplate (romiplostim), developed by Amgen, of Thousand Oaks, California; and Promacta (eltrombopag), developed by GlaxoSmithKline and Ligand Pharmaceuticals, of San Diego, California. Cinryze, a plasma-derived human C1 inhibitor, gained approval for hereditary angioedema, which is also rare.
In some cases, ultra-niche indications (those with less than 1,000 patients) can lead in to mainstream areas with more commercial potential, says Andrew Weiss, pointing to the research of Mark Fishman, president of Novartis Institutes for BioMedical Research in Boston. His work on the genetically inherited autoimmune condition Muckle-Wells syndrome (MWS) yielded ACZ885 (canakinumab), an anti-interleukin-1 (IL-1) beta antibody. The product is undergoing regulatory review for MWS, but it also could have potential in rheumatoid arthritis, psoriasis, type 2 diabetes and other conditions. "From that point of view you may see more activity in ultra-niche indications," says Weiss.
Regeneron Pharmaceuticals, of Tarrytown, New York, is following a similar strategy. It gained approval in MWS and related cryopyrin-associated periodic syndromes last year for a fusion protein called Arcalyst (rilonacept), which blocks IL-1 beta by acting as a soluble decoy receptor. It is now testing the product in patients with gout.
Edward Stuart of HS LifeSciences is critical, however, of the increasing focus on specialty medicines, which he says misses the most significant contribution that biotech can make in medicine: bringing high levels of innovation to bear on major medical problems. The focus on specialty medicines, he says, is driven by the short-term concerns of venture capital funds. "They have systematically tried to beat the innovation out of companies and turn them into specialty pharma companies," he says. "There's nothing wrong with that, but they shouldn't dress it up as biotech."
[Box 2]
The Pfizer-Wyeth merger has some worried that a wave of consolidation may occur among large pharmaceutical firms, leaving cash-strapped biotech companies with fewer potential partners or buyers. The Pfizer-Wyeth merger already scuppered one deal: Wyeth's reported $1.35 billion bid for the vaccine maker Crucell, of Leiden, The Netherlands. But not all pharma firms are planning to take the mega-merger route. London-based GlaxoSmithKline CEO Andrew Witty and Basel, Switzerland–based Novartis CEO Daniel Vasella both recently ruled out such a move, saying they would continue to seek smaller transactions and diversification. AstraZeneca, of London, has said it doesn't need a merger to help itself.
It's not easy telling pharma's future anyway. Edward Stuart of HS LifeSciences points to the recent appointments of new CEOs at many of the top ten pharma companies—including Severin Schwan at Roche, which is attempting to buy Genentech (see p. 212). The fresh blood could affect the culture and the partnering behavior of the companies concerned, and it's hard to know in what direction they will pilot their ships. "These guys are the next generation," he says. "All of these guys are going to put their approaches to work in their [respective] companies." But the basic overall dynamic of big pharma–biotech partnering is unlikely to change dramatically. "I'm guessing it might be difficult to get the attention of the Wyeth business development people in the next couple of weeks. I don't think it's going to take them out of the game in terms of the deals they were looking at," says David King, who sold one of his ventures, the protein engineering firm BioRexis Pharmaceutical, of King of Prussia, Pennsylvania, to Pfizer in 2002.
To decide if the UK's NHS should pay for a drug, NICE assesses the treatment's additional cost over that of the current standard therapy, set against the extra health benefits it confers. The tool for comparing the value or health gain of different drugs is the quality-adjusted life year, or QALY, which, at its crudest, measures the increase in life expectancy and quality of life derived from any treatment.
The main difficulty with QALYs is that this measure does not take account the severity of the underlying condition. A second major problem is the question of who decides what is an acceptable cost per QALY. Any drug with a cost per QALY below £20,000 will automatically get the nod; those between £20,000 and £30,000 will need additional evidence; and it is rare for drugs with a cost per QALY of over £30,000 to be approved.
Given an unacceptable price per QALY, there are two ways forward for companies to get NICE's approval: provide more compelling data for benefits or lower the price. In Australia, negotiating price is an explicit part of the HTA process. Similarly, in France the clinical added value, as determined through an HTA, is the key factor in agreeing on a price.NM
alcohen - From the name I assumed that the curepeyronies website was one designed to extract money from desperate people via products which don't actually work. Upon actually visitng the site though, it appears that the guy has good intentions and is simply presenting info and looking towards the future for more useful treatments.
I have already posted about IN-1130 (http://www.ncbi.nlm.nih.gov/pubmed/19473283?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum). That study was promising, but I should point out that just because a study in rats is successful, it doesn't always follow that it will be useful to humans. There is of course a chance that it will though, so it will be interesting to hear more about IN-1130 in the future. The sooner the better.
It is important to be aware that new potential treatments are moving forward RIGHT NOW in trials around the world. Here is just one example:
Quote from: Hadassah Blog
A Treatment to Swallow (http://hadassahsc.wordpress.com/2009/06/29/a-treatment-to-swallow-by-wendy-elliman/)
Hadassah doctors, working with Harvard Medical School, are researching a groundbreaking liquid therapy to target and prevent autoimmune diseases. ... Thirty days later, the patients who follow these directions and swallow the liquid daily will find themselves free of their diabetes, lupus, multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis or whichever of the more than 80 other distinct and crippling auto-immune illnesses dispatched them to their doctor. ... "At this stage, we don't even know whether our compound will be a treatment or a full cure," says Dr. Ilan. "But we're optimistic. We believe the trials will show that it has the capability to repair the basic defect that triggers the autoimmune disease process, and will thus be effective against the whole range of such illnesses. And this is a belief shared by several pharmaceutical multinationals, which show interest in investing in our project."
- George
:o
That's amazing!
so when will we be able to use this you think????
Quote from: Iceman on July 01, 2009, 09:11:17 PM
so when will we be able to use this you think????
This one is "out there" a ways. How long is anyone's guess. I suggest you read the full article to get a better picture if you haven't already. AND remember, this is just ONE of a number of very promising approaches. The big thing to remember is that now many diseases are being lumped into one target, so that modifying one biological pathway will treat or cure multiple diseases. This is VERY good for diseases like Peyronie's that otherwise would receive little attention. And all of this is being accelerated by the power of the Internet to enhance communication, the rapid accumulation of knowledge and the power of computers to sift through it, AND the growing transformation of developing countries into developed countries with maturing medical research programs. - George
Wow, George, that's an amazing find. Modern medicine is trying to "move up" in the command structure of the body, and it seems like this compound - if it works as advertised - will be doing just that.
Imagine, one teaspoon a day for a month and you can hit 'reset' on most major autoimmune disorders. It's good news for our affliction, but it's great news for people with MS, arthritis, and diabetes. Here's hoping it's all that little-known blog talks it up to be.
Here is a little hope to share on the Xiaflex front. My understanding is that it will be reviewed by the FDA on September. I will definitely seek out a doctor willing to use it off-label a.s.a.p.
http://video.aol.de/video-detail/frozen-finger-fix/446064678
This is a video of patients with Duprytens but they are reporting a 90% success rate in the trial group receiving Xiaflex.
My belief is that for a consistent study, the doctors are told to make a direct injection into the plaque. I have seen Dr. Levine perform the procedure with interlesional verapimil where he more aggressively moves the needle through the plaques to not only break them up, but to evenly distribute the verapimil throughout the plaque. My belief is that a technique like this applied to Peyronie's with Xiaflex could enhance results for those receiving the treatment. Add on top of this Pentox for any subsequent injection site issues and traction and our army of other treatments, and I believe success can be enhanced.
Food for thought.
Ted, thanks for the video link. I have 2 bent fingers waiting for Xiaflex. I recently had a thumb straighted (partially) by a hand surgeon using the minimally invasive technique called needle aponeurotomy. Xiaflex injectinos should be quite a bit gentler than what I just went through for the thumb.
As can be seen in the video, this stuff works - on fingers. Whether it will work on Peyronie's has yet to be seen, but as you point out, the key is probably going to be more sophisticated ways of injecting it.
Xiaflex has risks, though. Since it literally dissolves collagen, and doesn't necessarily know "good" collagen from "bad", it has to be carefully targeted.
Quote from: j on July 10, 2009, 09:50:08 PM
Xiaflex has risks, though. Since it literally dissolves collagen, and doesn't necessarily know "good" collagen from "bad", it has to be carefully targeted.
J,
I saw the video also, and it looks and sounds like good news for your condition!
However, what's your basis for stating that Xiaflex doesn't necesarily know "good" collagen from "bad" collagen?
CF
Ted,
The video says 80% success rate, not to be a debby downer, just didn't know if you missed that? Either way thats pretty impressive to me. That lady looked pretty happy. If that works on my penis my smile will be 10 times that much, don't want to get to fired up yet though. I don't know if the damaged tissue is the same in the hand as in the penis. One thing I noticed is they had 1,000 patients, thats a pretty big sample size....
J,
I would think "bad" collagen is not longer collagen, but fibrotic tissue, thats more a more deeply wound spiderweb, perhaps the medicine can recgonize the difference. That lady didn't appear to have any damange from it?
Comebackid
Xiaflex is just a trade name for collagenase. The "ase" suffix basically means "dissolves". It dissolves collagen. Many structures in your body are made of collagen, and there are different types of collagen. I believe Xiaflex targets one type; but that type also occurs in healthy tissue. So you can't just inject collagenase anywhere, the results could be very bad.
For Dupuytren's, they inject Xiaflex into the interior of a cord, with the intent of dissolving enough of it - from the inside out - that it is weak enough to snap. The woman in the video described how the doctor let the collagenase work for a while,then pulled the finger straight, snapping the cord. They're trying to keep the action of the Xiaflex confined inside the unwanted Dupuytren's tissue.
There have also been some immune system reactions to the Xiaflex injections, causing inflammation.
A few links, because sometimes a starving man can make do with the faintest whiff of food to get him through the hunger.
http://www.medscape.com/viewarticle/584669 -- this seems like a stretch, as they're identifying cardiac fibroblasts. But even if this exact drug has no Peyronies Disease applications, it's an exciting step into getting at the genetic triggers that cause fibrosis.
http://www.promedior.com/randd_SAP.html -- This is more long-term, but harnesses the bodies own cells to mediate fibrosis. As an aside, I think it's crazy that as a resident of SE Pennsylvania, both Xiaflex and this company are located in the town next to my office. If only I could go knocking on their doors with a fistful of cash for a quick hit of Peyronies Disease meds! :p
Has anyone else been concerned about the apparent change in Neprinol formulation? A bunch of sites and people are claiming that Neprinol isn't really Neprinol anymore, and that you have to get something called Serracor-NK to get the original formulation that worked so well.
As in:
http://www.biomediclabs.com/systemic_enzymes
and
http://gentlehugs.wordpress.com/2009/06/17/why-did-i-switch-from-neprinol-to-serracor-nk/
Any thoughts on this? I couldn't find anyone talking about this on the forums.
I have heard from someone at my urologist's office (though not confirmed) that there will definitely be a next phase of Xiaflex trials. Does anyone have any information about this?
I don't know where to post this seeing as the threads regarding Auxilium Pharmaceuticals have been locked. Basically I wanted to let people know that clinical trial of AA4500 is in its 2nd phase, with results expected in October of this year.
http://clinicaltrials.gov/ct2/show/NCT00755222?term=peyronie&rank=1
I don't know why those threads were locked, or why no one posted this crucial follow up yet. As I mentioned elsewhere, more needs to be done to raise awareness about this disease. This section of the forum is a good place to start.
For those interested, Baylor College of Medicine is recruiting participants for a Botox study on Peyronie.
http://clinicaltrials.gov/ct2/show/NCT00812838?term=peyronie&rank=2
Good luck.
Maverick, I think that trial is the one just completed, regarding which there have been a lot of posts. We're all hoping that when the results are announced in Octrober that they'll be more positive than what one might conclude from what we've heard so far.
Botox? Sounds hokey to me. Why would Botox have any effect on fibrosis?
Quote from: j on August 04, 2009, 02:45:44 PM
We're all hoping that when the results are announced in Octrober that they'll be more positive than what one might conclude from what we've heard so far.
IMO, no need for anyone to conclude anything from the few posts made on this board in regards to their alleged participation in Auxilium's trial.
CF
What is the science or concept behind the use of botox for Peyronies?
Jayhawk
Quote from: jayhawk on August 04, 2009, 03:39:14 PM
What is the science or concept behind the use of botox for Peyronies?
My guess is the analysis went something like this:
1. Botox works by blocking nerve receptors for muscle fibers, thus paralyzing those muscles. If the muscle's contraction was causing a visible wrinkle, that wrinkle is reduced.
2. Most people don't really understand what Botox does, and think it just smooths things out, somehow.
3. Lots of people are making tons of money selling Botox injections.
4. They'd like to make tons more by selling it for other conditions, even if it doesn't work.
5. One way to accomplish #4 would be to do an actual clinical trial for Peyronie's, using fuzzy and misleading success criteria so the results can be easily "spun".
I have communicated with the physician in the Botox trial. It is his contention that inserting the needle into the plaque dislodges it to a certain extent and he hopes to prove that the Botox inhibits reformation of this plaque. This does not seem likely to me, but who really knows at this point.
Quote from: ocelot556 on July 02, 2009, 06:24:42 PM
Wow, George, that's an amazing find. Modern medicine is trying to "move up" in the command structure of the body, and it seems like this compound - if it works as advertised - will be doing just that.
Imagine, one teaspoon a day for a month and you can hit 'reset' on most major autoimmune disorders. It's good news for our affliction, but it's great news for people with MS, arthritis, and diabetes. Here's hoping it's all that little-known blog talks it up to be.
and psioriasis, hair loss, dermatitis, allergies, the list goes on.
Quote from: ohjb1 on August 04, 2009, 05:45:09 PM
I have communicated with the physician in the Botox trial. It is his contention that inserting the needle into the plaque dislodges it to a certain extent and he hopes to prove that the Botox inhibits reformation of this plaque. This does not seem likely to me, but who really knows at this point.
If that's the angle of the trial then the objective seems quite weak. Ultrasound would be far more effective in breaking apart plaque, and it reformation would be dependent on a person's immune system (which could be boosted with other drugs). A combo of ultrasound and Botox would be a step in the right direction for a clinical trial, but then there are two variables instead of one.
Peyronie's plaque is made up of collagen and bio-debris. It is the consistency of leather and ultrasound is not going to have any effect on it no matter how powerful. I'm not convinced that needle poking is going to do it any good either at least not over the longer term. As for Botox, guys, its a TOXIN. Hello! I think perhaps what they are trying to do here is poison the plaque. But I can assure you they won't be using my penis as a guinea pig. - George
I actually go to BCM Baylor College of Medicine where the doctor developed the Botox injections. My Urologist and the Doctor work in the same department. I asked my Uros PA about the trials. They are very tight lipped on the subject. If I remember correctly he told me they do not actually know what it will do until they have the trails going and see the results. He also went on to say that it was never tested on humans up to this point. He told me they believe that it might relax the scar tissue.
Iam going back on the 14th of August I will ask him for a recap and post what I find for you all. I just remember thinking like george999 Iam not going to let them use me for a guinea pig using Botox.
Woodman
I agree, Woodman!
I am reaching another point of desperation with this disease, being on the cusp of losing a relationship over my impotence, and even as wracked with emotions as I am I still can't bring myself to apply for the trials. I don't see any purpose to sticking your penis with botox. I wonder what kind of men would, or how desperate, especially since Xiaflex - which isn't a paralyzing toxin - is just around the corner?
Quote from: George999 on August 04, 2009, 09:56:02 PM
Peyronie's plaque is made up of collagen and bio-debris. It is the consistency of leather and ultrasound is not going to have any effect on it no matter how powerful. I'm not convinced that needle poking is going to do it any good either at least not over the longer term. As for Botox, guys, its a TOXIN. Hello! I think perhaps what they are trying to do here is poison the plaque. But I can assure you they won't be using my penis as a guinea pig. - George
Hi George. I'm curious as to why you say that ultrasound will not have any effect. Ultrasound can vary in intensity and power based on the application necessary. Focused ultrasound can break gall or kidney stones apart and has been used in medicine for years. Molecular vibration can just as easily break apart plaque or tissue. Have you seen the post of the article from the American Journal of Physical Medicine & Rehabilitation?
https://www.peyroniesforum.net/index.php/topic,68.msg3571.html#msg3571
All I can say is that there is some reason that ultrasound hasn't gained any traction and I would guess that would be because other current approaches just work better. There are a number of studies out there that tout one or another success in dealing with Peyronie's, but then you pick up comments from people who have actually used those methods and got no perceived benefit and you just wonder. I prefer simple approaches like Pentox where the majority of people who try it actually feel they are benefiting from it. But in the case of ultrasound, 1) I don't understand how it can work on soft tissue like plaque without also damaging healthy soft tissue and 2) The comments I see from people who have tried it are not encouraging. And somehow I see the same rabbit trail with Botox. But who knows? Botox might be a dark horse that surprises all of us, but I'm not holding my breath. But I have to admit, either of the above make more sense to me than acupuncture AND I would be ecstatic if you could prove me wrong on ultrasound, so go for it! - George
Well, what about calcified plaques? I assume the reason it's safe to use on gallstones and such is because the stones themselves are more dense than the surrounding tissue - thus, different frequencies needed to break them up that are harmful to the stones, but not to the surrounding tissue.
Couldn't that be the case with Peyronies Disease plaques? I agree about the point of "soft tissue", but if those plaques have calcified, they've got to be more dense than the surrounding tissue.
I agree with George on this one, simply because of the negative feedback that ultrasound has gotten. Even Thacker's Formula has people who claims it cured them - I haven't seen one person attribute ultrasound to their recovery in anything but pain (which, as we know, can be treated in a whole host of ways without having one degree of effect on bend/plaque size/ed).
Quote from: ocelot556 on August 06, 2009, 03:53:23 PMWell, what about calcified plaques? I assume the reason it's safe to use on gallstones and such is because the stones themselves are more dense than the surrounding tissue - thus, different frequencies needed to break them up that are harmful to the stones, but not to the surrounding tissue.
OK, yes of course, that would work. In the case of gallstones, the debris from the stones gets flushed out the duct. In the case of Peyronie's the debris from the calcification goes ... where? - George
Quote from: ocelot556 on August 06, 2009, 03:53:23 PM
Well, what about calcified plaques?
If I had calcified plaques, I'd consider high dose vitamin K2-MK4, at 15mg/day up to 45mg/day (45 mg/day in three divided doses was safe in this study (http://pubmed.gov/12201222) of Japanese women. This is considered a pharmalogical dose. Note that this is K2-MK4, not K2-MK7.
s&s
Good point, George - but if the plaque is broken up via ultrasound, wouldn't it immediately become more pliant? A la the Leriche technique, by creating space between the binding tissue, you can extend it? I agree, though, it would be difficult to remove all calcification from the site. Of course, perhaps if you could break the calcified plaque down enough that a chelating agent might be more effective?
Haaa... this reads like a bunch to scientists working in a lab speculating what the big red button on the table does...
Ultrasound has many frequencies, power levels and hence applications. Focused high frequency high intensity ultrasound is the one used to break stones and has recently been used in treating/burning off fibroids in women (search for it on youtube) whereby the "focused" ultrasound directs the energy into one exact location, thereby creating enough energy at that location to essentially burn the tissue or break the stone. In regards to Peyronies Disease (rather potential Peyronies Disease application), the ultrasound used is not focused, and thereby creates vibrations over a larger surface area at the cellular/molecular level, stimulating tissue and increasing blood flow. Picture body tissue now, one side of which is softer and "healthier", and the other side which is harder and "unhealthier". Apply ultrasound at the invisible line where the two sides touch. Ultrasound creates vibrations so that this "line" starts to get blurred, and the blood flow from the healthy side starts to have openings and space where it can start getting into the unhealthy side and stimulating the area. The plaque being denser than the softer tissue, will actually be hit by more sound waves where since the cells are closer together, the waves are not able to pass right through. In the softer tissue where the blood flows freer amongst the cells, there is space amongst the cells to let the sound waves through.
That's a basic concept of ultrasound in regards to Peyronies Disease. Also, I'm not one to see the cup as half full, but I have yet to read on ultrasound therapy going wrong when applied to Peyronies Disease or other medically similar applications, so if anyone has concrete medical references or articles, please point me to them. I'm not saying this is a cure, I'm just wondering why more people don't try it.
OK guys, I see where your coming from on this and, as I said before, I'd be delighted to be proven wrong. I thoroughly agree that it should be investigated further. Once again, the problem becomes finding the funding, thats the ditch we always seem to end up in. :-\ - George
I think the term "plaque" just confuses things. It implies some sort of hard deposit that needs to be "broken up". And the term "calcified" suggests the mineral deposits in an old water pipe. The reality is - it's fibrosis, a tangle of collagen and fibrin molecules. These are proteins - the same ones found in normal, healthy. connective tissue. It's not something brittle that might be shattered by ultrasound.
I've never really understood use of the term "calcified". It's claimed that this tissue accumulates calcium over time but I have doubts abou the use of this word, too.
Those of us who also have Duputyren's contractures have a sort of sanity check to apply because Dupuytren's is the same thing in another area of the body - the tissue has been found to be virtually identical - and seems to be better understood than Peyronie's. With Dupuytren's the term "plaque" is never used, no one talks about "breaking up" the plaque, and ultrasound is known to have no effect. It's just fibrosis, period. Dupuytren's tissue doesn't "calcify" either.
Many things that have been suggested as treatments for Peyronie's have been tried for Dupuytren's years, or decades, ago and found not to work. Vitamin E, Potaba, various antioxidants, accupuncture, NSAIDs, antihistamines, and of course transdermal Verapamil are all ancient history in the Dupuytren's world, no longer even discussed. All sorts of systemic meds have been tried and in the end, Xiaflex (collagenase) is the only one to show real effect, and attract investment. Everything else has faded away.
I'm not sure that I totally agree with the previous message, but aside from that let's not forget about the inflammatory processes at work. All too often it's easy to look at peyronie's from the perspective of existing and often extensive fibrosis and so forth, but if future treatments are able to knock out the inflammatory processes very effectively and very fast, then for many men dealing with peyronie's may simply be a case of taking a short course of treatment to allow normal healing to take place.
I do hope that Xiaflex does hold a place to in teatment of long term sufferers of the condition though. Maybe in conbination with a wide ranging oral treatment regimen (to diminish reoccurence) and traction, thi could prove to be a urprisingly effective mix. The jury seems to be out of Xiaflex for peyronie's right now though.
Intead of saying that treatments don't work at all, maybe it's more accurate to say that they don't cure peyronie's.
Dupuytren's also causes inflammation early on, which was the reason for trying NSAIDs and antiistamines. I believe no one ever demonstrated success in stopping the eventual progression of the fibrosis, but that might be because no one tried hard enough. To me though these "inflammatory phase" ideas remind me of all the things that are supposed to cure a cold if taken at the very earliest stage - i.e. by the time you're sure you have a cold, it's too late, they only "work" when there's a 50% chance you don't even have one.
Research on ways to prevent Peyronie's by intervening in the "inflammatory phase" seems unproductive to me because no one seeks treatment at that point.
Quote from: j on August 08, 2009, 04:00:22 PM
Research on ways to prevent Peyronie's by intervening in the "inflammatory phase" seems unproductive to me because no one seeks treatment at that point.
I'm more interested in the efforts of those trying out new strategies and oral treatment combinations to attempt to give hope to peyronie's sufferers. This all sounds a bit doom and gloom to me. If people are not seeking treatment during the inflamatory stage, then we should enlighten them to the possibility of doing so, rather than assume that little can be done to help the situation. Doing something is always better than doing nothing.
It seems likely to me that the most promising future treatments may well relate to altering the immune resource to inflammation as soon as humanly possible, which is why it's worth exploring options like LDN. There is no way of knowing when a breakthrough will come, but with a proactive approach there is hope that we will stumble upon something. This in combination with treatments that are somewhat helpful (VED and so on), is a sensible approach to a difficult problem. What's the alternative?
QuoteDupuytren's also causes inflammation early on, which was the reason for trying NSAIDs and antiistamines. I believe no one ever demonstrated success in stopping the eventual progression of the fibrosis, but that might be because no one tried hard enough.
Used early on, radiation therapy appeared to be somewhat successful. I haven't checked out studies but on the forum there, people seem to be pleased with the results, so something positive appears to be happening: http://www.dupuytren-online.info/radiation_therapy.html I'm not suggesting this as a treatment for peyronie's, but rather trying to push the idea that we need to muster the motivation to really go all out looking for new treatment strategies, and maintain hope for others even if our own situation isn't great in all cases.
Have you all seen this non surgical treatment for Peyronies Disease?
(link disabled)
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I do not suffer from Peyronies Disease but I did use this product prior to becoming an affiliate and although it did not add the full 1.4 inches in length, it did add right at one inch in length.
Any new updates from those previously enrolled in the Xiaflex trials? We had something of a mixed bag before, with some people claiming improvement, or one that I can remember stating that his condition actually worsened.
My thoughts are:
- I wonder if the follow up they perform is sufficient. It's not beyond the realms of possibility that men could experience negative changes outside of the obervation period.
- As moderate brusing and swelling appear to have occured with some men (men prone to penile injuries escalating), maybe this can inhibit some potential improvement. Hopefully in combination with other treatments (oral, mechanical), this negative could be lessened. It stands to reason that getting on a good oral treatment routine early on in the peyronies lifecycle is useful, thus it would probably be a good idea for those undergoing xiaflex injections to do this too as a precaution. I suppose that's out of the question during the initial trials, but in the long run, it would make sense.
Quote from: newguy on August 15, 2009, 09:11:36 PM
Any new updates from those previously enrolled in the Xiaflex trials? We had something of a mixed bag before, with some people claiming improvement, or one that I can remember stating that his condition actually worsened.
newguy,
I too appreciated the fact that some men took the time to post about their experience.
However, I'm infinitely more interested in the company's actual report than anecdotal stories from those claiming to be a part of the trial. This is because many members will engage in mere speculation on the treatment's potential based on a forum post. In fact, the self-alleged trial participants have to speculate themselves as to whether they even received Xiaflex as opposed to the placebo!
CF
"In fact, the self-alleged trial participants have to speculate themselves as to whether they even received Xiaflex as opposed to the placebo!"
Yes, that's very true. I guess we have to play a waiting game for now.
I notice that phase 3 trials for Xiaflex for Dupuytren's have resumed: http://www.medicalnewstoday.com/articles/79922.php
There is a recent interview with Auxillium executives and I don't see much in the way of a discussion about a decrease in curvature due to Xiaflex. Hope I am wrong, but this may be a bad sign.
http://seekingalpha.com/article/135832-auxilium-pharmaceuticals-inc-q1-2009-earnings-call-transcript?source=yahoo&page=10
ohjb1 -
They are somewhat limited as to what they feel comfortable in stating. The previous results (in study A) revealed that a 25% reduction in curvature "was achieved at three and six months with 58% and 53% of patients, respectively". This to me is not exactly a resounding success, and surely the three and six month differences actually mean that some mens curvature initially improved, but then increased somewhat between that period (from the point of improvement, not the starting point - i don't want to scare people :)).
Not to put a total downer of it though, as it very much appear that the treatment program does play a large part in the success or otherwise of the treatment. Study B which effectively involved receiving more injections resulted in 25%+ improvement in 8 out of 9 patients. I'm unsure of whether modeling (via a traction device I assume?) was used in these phase IIb trials, though it was used in phase IIa. The comment regard it from Auxillium, well I couldn't quite figure out how it applied to the latest trials:
"The other piece that we are testing is whether or not modeling works or doesn't work. One of the studies had modeling, the other one didn't. The one that had modeling in the previous IIa had somewhat higher and a more sustained effect, but we are testing that at this particular point in the trial."
Auxilium did note that " the FDA, in our discussions with them prior to the initiation of this trial, really encouraged us to go down the pathway of developing the patient reported outcomes, because they believe that a greater than 25% reduction in angle, if it doesn't translate into meaningful improvement in sexual activity, reduction in pain, and some of the other domains, probably isn't a valid objective endpoint.". This suggests that there are doubts over whether a 25%+ improvement is enough to make this worthwhile. Hopefully they will decide that it is worthwhile.
Phase 3 trials could be happening next year. If the improvement was, say 50% I think that would be reason to be really happy about all of this. If it does make it to markey though, use of Xiaflex in combination with other treatments could still make the difference to an awful lot of men. Time will tell how this pans out.
Thanks for your reply. Just a few follow up comments. I was in the phase IIb trial and was in the modeling group. Secondly, everyone in phase 11b who received Xiaflex as opposed to the placebo received the same dosing as those in the previous trial who reported 8 out of 9 participants who improved. Of course, we do not know who received the placebo and we are speculating. FYI - There has been no change in my condition.
Are you aware of many other men is the study and how their condition fared after the treatment? Are you under the impression that you received a placebo, or xiaflex? Of course it's of limited use to discuss these things when compared to the released results, but it's of interest to speak to someone who went through the process.
Newguy - don't know anything more about other men other than what I read on this forum. One member contacted my privately and also said no change in his condition after the trial. Whether i received Xiaflex or placebo, really don't know. Some forum members believe that if there was bruising they recevied the real thing. My urologist said this is not the case as the insertion of the needle into the plaque results in bruising. Basically, we are in the dark until the results of published.
The treatment probably wasn't agressive enough.
For Dupuytren's they injected Xiaflex, let it work for a while to weaken the tissue, then tried to forcibly straighten the finger and snap the cord. And I mean "forcibly". The injection of Xiaflex on its own wasn't powerful enough to simply dissolve the cord and release the finger. They're afraid that if they injected enough Xiaflex to do the job on its own, there'd be collateral damage to surrounding "good" tissue.
With Peyronie's they're dealing with a more delicate structure and so I think they were even more conservative. As a result they didn't break up enough tissue, in most cases, to cause a truly useful change.
This was probably not a surprise to Auxilium. To get FDA approval you need to show complete safety but only very modest positive effect. This is why we often end up with widely prescribed big-name drugs that really aren't very effective, and sometimes long term followup studies show that they're a waste of money. Once FDA approval is secured, a drug company may stop spending money on additional research and just pour it into massive advertising campaigns. I hope that doesn't happen here, and that Auxilium works on improving the effectiveness of Xiaflex treatment.
This forum can have a real impact on what Auxilium decides to do.
Hmm so would you say that the treatment should involve an injection of xiaflex and then something to give and maintain an erection for awhile, so the xiaflex weakens the fibrotic tissue and the erection remodels the shape?
Maybe more injections over a wider area; maybe in combination with a stretching device or VED; maybe several treatments over a period of time. I don't want to speculate too much further because I'm not a doctor.
With Dupuytren's the corrective treatment can get pretty rough. With Peyronie's, a more sophisticated approach will be required.
I just talked with a doctor friend of mine in regards to these trials. He stated to me that the FDA is more concerned with safety as J has already stated. They are probably overly concerned about this in my friends opinion, however they due it to protect potential patients. They are less concerned about effectiveness, once they get the clearness I think as J states there will be a much more aggressive treatment protocol. Really it could be many things. I'm looking forward to seeing some ultra sound evidence that the drug can really dissolve the peyronies plaque or tissue or modify it. VED could be used to help stretch the tissue if it is only made to be more flexible but not completely dissolved.
J is right in that this forum can have an impact on what this forum does. It is extremely important that we continue to work hard to grow our membership, as we are doing in the advocacy section of our forum, anyone who is interested come take a look, we are working on a mass mailing project to urologists to recruit more peyronies sufferers. We need to grow our membership, and at some point write a letter to Auxillium or leading urologists who have pull. J is absolutely right in that it is important once Auxillium gets the FDA safety clearance, they don't stop working on the effectiveness of this drug, otherwise we may not get the full cure we are looking and praying for here.
Comebackid
In the Dupuytren's trials, they had a couple cases of tendon damage:
http://tinyurl.com/mh95ux
The article at that link includes comments from a couple of hand surgeons who in my opinion are overly negative. I've had Dupuytren's surgery - it's rough, damage can happen (I had a nerve severed), recovery is long, infection is possible, scar tissue builds up - and surgeons tend to minimize all these risks. Many people feel that hand surgeons simply don't want to lose the income from Dupuytren's sugeries. I won't go that far, but I think they're instinctively resisting a non-surgical alternative. The surgeons quoted in this article do make a good point, which is that injecting Xiaflex requires a detailed knowledge of the target anatomy.
Xiaflex is potent stuff, biologically active - unlike all the snake oil we've been sold in the past - so some issues are to be expected.
J,
It could be possible doctors would resist a solution, as then they couldn't do surgeries and make $$$, since they get paid significant money based on procedures. However they'd have to be in bed with Auxillium wouldn't they? Wouldn't auxillium purposely have to be sabatoging their own product in xiaflex?
Comebackid
I'm not much into conspiracy theories. I'd just say that surgeons seem to be very conservative and not open to new ideas unless they come down from above, through the usual channels. Surgeons want to do surgery - it's what they know. Some, maybe most, of them also want the best deal for their patients.
The surgeons probably know how complex and variable the human anatomy really is - they see it from the inside - and they don't like the idea of some Beverly Hills MD adding to his Botox income by injecting Xiaflex and letting the lawyers deal with the mistakes. But in my experience, surgeons minimize the risks and downside of their own procedures.
Reading this article, I can see how urologists might be cautious about getting into this treatment.
Hey guys,
Saw this in the usa today, just found it interesting since we know phizer bought auxilium out and the right to market their drugs.
Phizer gets fined big time! (http://www.usatoday.com/money/industries/health/2009-09-02-pfizer-fine_N.htm)
Wow, thats a heck of a fine to pay, I wonder if that will negatively effect the company's ability to market or develop future drugs like xiaflex?
I was reading up on off-label usage, I did not know it is legal to prescribe medications for off-label usage, but illegal to market them. So really anyone in this forum who is taking pentox for peyronies is using an drug for an "off-label" purpose.
Off-label use is the practice of prescribing pharmaceuticals for a purpose outside the scope of a drug's approved label - an unproven, untested use - most often concerning the drug's indication[citation needed]. In the United States, the Food and Drug Administration (FDA) requires numerous clinical trials to prove a drug's safety and efficacy in treating a given disease or condition[citation needed]. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route and other information to be included on the drug's label. More detail is included in the drug's package insert.
However, once the FDA approves a drug for prescription use, they do not attempt to regulate the usage of the medicine, and so the physician makes decisions based on her or his best judgment. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off-label, including controlled substances such as opiates. Actiq, for example, is commonly prescribed off-label even though it is a Schedule II controlled substance. However, it is unlawful to market, advertise or otherwise promote the off-label use of drugs, including controlled substances.
Off-label use of medications is very common. Up to one-fifth of all drugs are prescribed off-label and amongst psychiatric drugs, off-label use rises to 31% (Radley, et al. 2006).[1] New drugs are often not tested for safety and efficacy specifically in children. Therefore, it is believed that 50-75% of all medications prescribed by pediatricians in the U.S. are for off-label applications.[2]
Some drugs are used more frequently off-label than for their original, FDA-approved indications. A 1991 study by the U.S. General Accounting Office found that one-third of all drug administrations to cancer patients were off-label, and more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society found that 60% of them prescribed drugs off-label. [3]. Frequently, the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs. An example is the use of tricyclic antidepressants to treat neuropathic pain. This old class of antidepressants is now rarely used for clinical depression due to side effects, but the tricyclics are often effective for treating pain.
Off-label use (http://en.wikipedia.org/wiki/Off_label)
QuoteInjectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture
Methods We enrolled 308 patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial. The primary metacarpophalangeal or proximal interphalangeal joints of these patients were randomly assigned to receive up to three injections of collagenase clostridium histolyticum (at a dose of 0.58 mg per injection) or placebo in the contracted collagen cord at 30-day intervals. One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection. Twenty-six secondary end points were evaluated, and data on adverse events were collected.
Results Collagenase treatment significantly improved outcomes. More cords that were injected with collagenase than cords injected with placebo met the primary end point (64.0% vs. 6.8%, P<0.001), as well as all secondary end points (P0.002). Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo (from 43.9 to 80.7 degrees vs. from 45.3 to 49.5 degrees, P<0.001). The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness. Three treatment-related serious adverse events were reported: two tendon ruptures and one case of complex regional pain syndrome. No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed.
Conclusions Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. - http://nejm.highwire.org/cgi/content/abstract/361/10/968
Of course peyronie's only has a limited amount of common with Dupuytren's (it would probably be unwise to attempt to manipulate the penis in the same way you'd manipulate a joint - other than by light traction) . That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less.
That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less
Newguy, what peyronies results with xiaflex are you referring to, I thought that auxilium has not published any results yet unless I missed something? ???
ComebackKid - I was refering to the info out there thus far, and not any new results. I look forward to us receiving any updates relating to how effective this treatment actually is.
Quote from: newguy on September 04, 2009, 07:05:07 AM
That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less.
Newguy,
with all due respect (you're one of my favorite posters), your statement (see above, emphasis supplied by me) is conclusionary and is not supported by any
cited sources.
I believe you may be referring to a conference call provided to primarily the investment community, and if I recall, the company did not publicly reach the conclusion that you have. Or, even less authoritative, posters alleging to have participated in the trials.
Another point (and, I may be way off base here), regarding drug research on trial participants, the actual participant results that "we" may conclude are not "impressive" may in fact be of invaluable information to the researchers. Meaning, the results provide them with information that they can use to "optimize" the drugs use.
So, although I appreciate your interest in the Xiaflex trials, I cannot agree with your above statement and it may cause other readers to become disillusioned.
thanks for all your efforts!
CF
Hi cowboyfood. My comments are based on the reduction of most of the joint contractures in dupuytren's patients to between 0-5 degrees. The early clinical trial results for peyronie's revealed a 25%+ reduction in curvature. It may be the case that some of those improvements were very significant, or that the technique can to has been refined to maximise the potential of xiaflex, so I would not wish for anybody to be disillusioned. Should the treatment become available to us all at some stage, and ill effects or complications are minimal, maybe it will be possible to successfully combine it with other treatments or have further injections. I'm as much in the dark as anybody really and hope that future announcements from auxilium.com are promosing.
Strictly speaking the effectivness of the dupuytren's trials are as probably as much to do with the nature of the condition (that once the the scar tissue is sufficiently weakened it can be totally released from the underlying tissue), which differs from that of peyronie's disease. Again, Xiaflex may potentially offer an almost instant reduction in curvature for many individuals, so I don't want to put a downer on it. It's certainly a treatment of interest.
Thanks for your posts too :). I really don't mind people disagreeing with what I write, as its healthy to have ideas challanged and to be corrected if I make statements that cannot be 100% backed up.
Quote from: newguy on September 05, 2009, 05:40:37 PM
Strictly speaking the effectivness of the dupuytren's trials are as probably as much to do with the nature of the condition (that once the the scar tissue is sufficiently weakened it can be totally released from the underlying tissue)...
That's partially true. Dupuytren's contractures may or may not be strongly adhered to the surrounding tissue. When there is a lot of adhesion the contracture can only be released by surgery, and that may be only partially successfull. Contractures in the palm tend to have much less adhesion, and be easier to release by 'snapping', than contractures further out in the fingers.
J - Yes, I read a few stories about how surgery doesn't always go to plan, and can occasionally result in nerve damage etc. I suppose it's something worth catching early to maximise (the limited) treatment options. Radiation therapy appears to be all the rage on the dupuytrens forum for early stage intervention.
Quote from: newguy on September 05, 2009, 05:40:37 PM
The early clinical trial results for peyronie's revealed . . .
newguy,
thanks for the response. do you have a link or a document with these "early clinical trial results?" Or, maybe it's already posted somewhere on the forum.
CF
CF - I think numbers here is all we have so far: http://www.auxilium.com/ProductPipeline/PeyroniesDisease.aspx It's very limited but at least it suggests that they are fine tuning their technique.
Forgive me if this was already posted...looks like its from May of this year...
http://www.ncbi.nlm.nih.gov/pubmed/19473283?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
I missed that one (I follow for any publication that uses "Peyronie's Disease" as a key term having the medical library scan for it weekly).
It is very exciting news. The issue I wonder about is this: are there multiple forms of Peyronies that have different inciting events and pathways to fibrosis. This blocks it (and more excitingly - it causes regression!) in a rat model of disease. I wonder how it might work for you or me.
Tim
Nice find -- thanks.
QuoteAntagonizing TGF-beta signaling through the use of ALK5 inhibitors may represent an exciting new therapeutic strategy for the future treatment of Peyronies Disease.
Leads me to wonder what other ALK5 inhibitors are out there. The study cited used IN-1130.
It was posted a while back: https://www.peyroniesforum.net/index.php/topic,36.msg20393/topicseen.html#msg20393 Certainly looks like something of interest.
QuoteAdvanced glycation end products (AGEs) contribute significantly to diabetic complications, both macro- and microvascular. TRC4186 is an AGE-breaker that has been evaluated in vitro and in vivo and shown to reduce AGE burden. The aim of this study was to determine the effect of TRC4186 on diabetic cardiomyopathy and nephropathy in obese Zucker spontaneously hypertensive fatty rats (Ob-ZSF1), an animal model of diabetes with progressive cardiac and renal dysfunction. Ob-ZSF1 rats loaded with 0.5% salt were treated with TRC4186, 9 or 27 mg/kg twice daily intraperitoneally or vehicle control and monitored telemetrically throughout the study. Cardiac function was assessed terminally by Millar catheter. Markers of cardiac and renal dysfunction were measured and changes evaluated histopathologically. TRC4186 at 27 mg/kg prevented rise in blood pressure (BP) and also improved cardiac output (CO) secondary to better diastolic relaxation as well as systolic emptying in association with the reduction in afterload. At 9 mg/kg, CO was improved by compensatory increase in pre-load however afterload reduction was not adequate to allow efficient systolic emptying. Brain natriuretic peptide (BNP) and interleukin-6 (IL-6) expression was reduced with treatment. Deterioration in renal function was retarded as evident from albumin to creatinine ratio and renal histopathology. TRC4186, an AGE-breaker, clearly preserved cardiac function and reduced the severity of renal dysfunction in Ob-ZSF1, an animal model with persistent severe hyperglycemia leading to diabetic heart failure and renal failure.
- http://www.ncbi.nlm.nih.gov/pubmed/19546815?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Another AGE-breaker working its way through the system..
Regarding your remark, in your most recent statement below, on how well the treatment might work for humans, do we need to consider that a mouse's life is much shorter than a human's and therefore calculate the time accordingly. Do you, or anyone else on the forum, know what 45 mouse days is in human days, or years?
I really think that what we learn through the IN-1130 study is that if one can block or stop TGF-beta1 effectively enough, one can REVERSE Peyronie's effectively returning penile tissue to NORMAL. That would be a HUGE achievement which everyone here would cheer. It indicates that the reason Pentox is so ineffective is because it simply does not block TGF-beta1 sufficiently to effect an outright reversal. It does block it enough to thwart its progress and initiate a feeble reversal. ALL of this is more evidence for autoimmune processes being the driving force behind Peyronie's. Remove that factor and everything goes back to normal. So what are the flies in the ointment for IN-1130? I see some big ones. First of all, TGF-beta1 is an essential cytokine which has a lot of legitimate immune functions. If we block it completely, we could run into unexpected consequences like cancer or vulnerability to infectious disease. In order to avoid those pitfalls, one has to specifically block ONLY the autoimmune pathways while allowing normal immune pathways to remain functional. I really don't know whether IN-1130 is a SELECTIVE TGF-beta1 blocker or a brute force broad spectrum blocker. A broad spectrum blockade would be scary to me. - George
Why was this study being done in korea? Aren't there more studies going on in the united states or a bigger country with more doctors? ???
Could one obtain this drug for usage? Is it as safe as pentox, what do we know about it , or should I say what do the medical experts know about it, how safe is it?
The real question I have is what if one used this drug and it was effective, for a complete reversal of peyronies, then quit using it, would the peyronies come back? Perhaps a few months on it could outweigh the risk of getting diseases if it works and we know it works.
A IN-1130 study here includes an email address from a college of pharmacy should anybody wish to attempt to follow this one up:
http://www.informahealthcare.com/doi/abs/10.1080/00498250701871121
College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-ku, Seoul 120-750, Korea, 82-2-3277-3028, 82-2-3277-3051 yysheen@ewha.ac.kr
this is interesting and could provide an option for getting medication into the tunica one day for you younger sufferers
"A cream allowing erectile dysfunction drugs to be applied directly to the skin could one day make them safer to use, say New York scientists. Studies in rats suggest that Viagra, Levitra and Cialis could pass through the skin in tiny capsules, they say."
Full article here
http://news.bbc.co.uk/1/hi/health/8263307.stm
Quote from: UK on September 19, 2009, 02:39:04 AM
Full article here
http://news.bbc.co.uk/1/hi/health/8263307.stm
Very interesting. It reminds me of topical ibuprofen where the topical version provides a similiar level of relief, but very little of it circulates beyond that area. In studies where viagra has helped to inhibit fibrosis in rats, much higher doses than we are able to take were used. If in future it can be intensely targetted in such a way, maybe it will be much more effective.
thanks to all people for sharing and advice me very informative info.
keep sharing in future also.
Thanks for the heads-up on this research. I am going to Email some of these links to urologists in my region so they can get us involved in these studies.
Back to the subject of heat treatment, I have always thought that there may be a temperature trigger which may cause or promote Peyronies Disease. Testicles are situated outside the body because a lower temperature favours sperm production. The penis is in a similar - even more 'exposed' environment, so could it be that the lower temperature it experiences causes plaque to form there when certain other factors are present.
I would certainly try heat treatment, but I don't know of any (safe) gadgets available for localised application.
Regards
Percival
Further to my earlier post I have tried applying a thermal heat patch to the affected area. It seems to stay in place in my underpants and gives out a gentle heat all day - it is rather pleasant. Don't know if it will do any good though! I am also trying Pentox, Arginine and daily Cialis. Also trying traction: first results after a month are encouraging. I think that the plaque had bunched up and the traction has pulled it straight and given back a little length.
One word of warning concerning thermal patches - there are many on the market so check that they don't get too hot. You may need to wrap them in a sock to moderate the output.
Warm regards
Percival
Saw this link in my random clinical trial searching... maybe it's been reported, maybe not - but it looks interesting! Arresting Suspect #1 in the inflammation cascade - TGF-Beta.
http://www.medpedia.com/clinical-trials/NCT00043706
"Excess Transforming Growth Factor Beta-1 (TGF-beta1) activity may result in the abnormal fibrosis characteristic of Systemic Sclerosis. An antibody against TGF-beta1 may modify pathologic processes characterized by inappropriate fibrosis. Genzyme Corporation is currently investigating a human monoclonal antibody (CAT-192) that neutralizes active TGF-beta1. This study is being conducted in the U.S. and Europe to evaluate the safety, tolerability, and pharmacokinetics of repeated treatments with CAT-192 in patients with early stage diffuse Systemic Sclerosis."
The problem I see with this approach is that it simply has to have significant negative side effects. The immune system produces TGF-beta1 for a reason. When you snuff out that metabolic function, there are bound to be negative consequences. - George
George999
Neprinol
I am really digging back to your old post from 2008. There doesn't appear to be anything directly related recently from anyone.
I have just completed my first round of 26 wks of VED 3 cyliner protocol. I recently switched to Ubiquinol , am taking PENTAX and L'Arginine. I am sorry to report that I have not yet had any noticable improvement in curvature.
Rifling thru my files from my initial diagnosis , I turned up an article on the product Neprinol as well as an article by Dr. Herazy.
Just wondering , now that I am beginning a new 26 wk protocol , if there is anything anyone can report on lately as to whether Neprinol can be taken in combination with the above , with some hope of success.
Thanks
Hello Mike,
Sorry you are not seeing results at this point, but I would advise you to be patient. It really takes a long time, but both Pentoxifylline and Ubiquinol DO work and so does the VED. But they don't work overnight. In my experience, Neprinol is useless for Peyronie's. It can really clear your lungs out and be beneficial in other ways, but for Peyronie's, its useless. Its very expensive and I've still got an old half full bottle around. I just gave up on it because it just doesn't work. Also, I am sending shadesofblue your way. He just posted under the Causes of Peyronie's topic. He's in Toronto and planning to make an appointment with Levine. I told him you were on to a good Peyronie's doc in Toronto. So if you could advise him on that I would appreciate it. Thanks! - George