Peyronies Society Forums

Please login or register.

Login with username, password and session length
Advanced search  

News:

Augusta Med System info for Australians
Link to post

Pages: [1]   Go Down

Author Topic: Highlights of Developmental treatments and drugs (Still in trials)  (Read 14327 times)

0 Members and 1 Guest are viewing this topic.

Liam

  • Major Contributor
  • ****
  • Offline Offline
  • Gender: Male
  • Posts: 1031
  • ...grab some scalpels and settle this like doctors
Highlights of Developmental treatments and drugs (Still in trials)
« on: September 13, 2006, 09:08:35 PM »

This area contains highlights from the main Peyronies Disease Discussion Forum topic on "Developmental treatments and drugs for Peyronies Disease (Still in trials),...".  This area contains information and links on new drugs and/or treatments being developed.

As with all the topics on this newly diagnosed board, these topics are read only highlights copied from the main forum.  Go to the main forum to join in the exchange by posting questions and comments.
Logged
"I don't ask why patients lie, I just assume they all do."
House

Angus

  • Administrator
  • *****
  • Country: us
  • Offline Offline
  • Gender: Male
  • Posts: 313
Highlights of Developmental treatments and drugs (Still in trials)
« Reply #1 on: January 16, 2007, 10:58:51 PM »

       The following is a one-post compilation of highlights from hundreds of posts in the Developmental Treatments thread. Individual posts have been copied into this page and no grammar or wording has been changed from the original post. Entire posts have been copied where possible to retain the context of the original post. The posts are entered in chronological order from the top of the page to the bottom, so the oldest posts will be read first and the most recent posts will be read last. This IS a work in progress and will be added to and edited so check back often.

Highlights from the thread Developmental Treatments and Other Drugs for Peyronies Disease




Dcaptain     Reply #16 on: September 24, 2005, 11:49:54 AM »    Quote

________________________________________
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.









J       « Reply #22 on: October 13, 2005, 10:19:27 PM »    Quote

________________________________________
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.





Larry H     « Reply #30 on: December 19, 2005, 02:34:10 PM »


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








Hawk       « Reply #34 on: April 20, 2006, 01:15:06 AM »    Quote

________________________________________
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.









Tim468               « Reply #39 on: May 30, 2006, 08:47:44 AM »    Quote

________________________________________
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.









Liam       « Reply #66 on: June 21, 2006, 12:10:35 AM »    Quote

________________________________________
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









Hawk           « Reply #74 on: June 21, 2006, 06:08:42 PM »    Quote

________________________________________
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.










ComeBackid                 « Reply #77 on: June 21, 2006, 08:57:03 PM »    Quote

________________________________________
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










Tim468                       « Reply #87 on: July 11, 2006, 09:20:43 AM »    Quote

________________________________________
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










Blink            « Reply #88 on: July 12, 2006, 08:52:42 AM »    Quote

________________________________________
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










Hawk            « Reply #98 on: August 11, 2006, 10:14:28 AM »    Quote

________________________________________
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.









Tim468           « Reply #99 on: August 11, 2006, 06:07:04 PM »    Quote

________________________________________
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








Tim468             « Reply #122 on: September 13, 2006, 11:09:02 AM »    Quote

________________________________________
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











Tim468           « Reply #129 on: September 30, 2006, 10:53:43 PM »    Quote

________________________________________
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










Mark501                     « Reply #145 on: October 25, 2006, 01:51:13 PM »    Quote

________________________________________
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.









Tim468                    « Reply #154 on: October 26, 2006, 10:46:32 AM »    Quote

________________________________________
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








Tim468                       « Reply #162 on: October 30, 2006, 09:39:09 AM »    Quote

________________________________________
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









Mark501              « Reply #171 on: October 31, 2006, 12:20:29 PM »    Quote

________________________________________
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.








LarryH              « Reply #189 on: November 09, 2006, 01:00:52 PM »    Quote

________________________________________
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.









Tim468                    « Reply #191 on: November 10, 2006, 09:51:24 AM »    Quote

________________________________________
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









Power                     « Reply #205 on: November 20, 2006, 03:34:39 PM »    Quote

________________________________________
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










Hawk                  « Reply #206 on: November 20, 2006, 03:49:11 PM »    Quote

________________________________________
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.










Rico               « Reply #237 on: January 10, 2007, 03:37:29 PM »    Quote
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........




George999       January 26, 2009
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 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


________________________________________

Logged
Pages: [1]   Go Up
 

Related Topics

  Subject / Started by Replies Last post
1121 Replies
309930 Views
Last post January 17, 2011, 10:51:11 PM
by George999
11 Replies
3215 Views
Last post November 22, 2013, 09:48:26 PM
by james1947
2 Replies
1251 Views
Last post May 07, 2014, 06:42:05 AM
by james1947