Developmental drugs & treatments - Still in trial or not approved for Peyronies

[Hawk]

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.

[Power]

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

[Hawk]

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.

[scott]

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

[Tim468]

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

[Larry H]

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

[Hawk]

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.  

[mark501]

Rico, Your remark about Dr. Jordan was nothing short of slander. There is no excuse for this  kind of behavior on this forum.

[ComeBacKid]

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

[ComeBacKid]

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

[George999]

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

[Rico]

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

[Tim468]

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

[Hawk]

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.

[Rico]

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

[Tim468]

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

[Hawk]

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.  

[Rico]

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

[Hawk]

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.

[ComeBacKid]

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.

[George999]

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

[mark501]

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.  

[ComeBacKid]

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.  

[ComeBacKid]

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

[Larry H]

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.

[Steve]

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

[Larry H]

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

[Hawk]

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

[Larry H]

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

[Hawk]

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

[Old Man]

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

[Hawk]

I was thinking of something nicer sounding like a testicular redistribution

[ComeBacKid]

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

[Larry H]

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

[Liam]

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

[Tim468]

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

[kevin]

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.

[ComeBacKid]

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.

[j]

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

[Larry H]

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

[Power]

Well stated Larry, Well stated!

Thanks for posting that. Timely indeed. Curtailing the bashing of AA4500 is certainly welcomed in my book.

Power

[Tim468]

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

[Steve]

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?

[George999]

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:

The 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

Be sure not to miss the section on the effect of BMP-7 on calcification!

[Tim468]

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

[Rico]

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

[hopeful]

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

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.  

[Liam]

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

[JW]

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

[Rico]

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 !

Maybe the report will be available soon in urotoday.....seems anti fibroid and cialias is a hot topic...

Rico..........