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

[Blink]

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  

[hopeful]

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....

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.

[scott]

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!

[mark501]

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.

[Power]

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

[Tim468]

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
-  

[Power]

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

[Rico]

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

[Steve]

  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  

Steve

[Tim468]

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

[ComeBacKid]

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.

[Rico]

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

[Ramjet]

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"

[Liam]

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

[kenm]

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?

[ComeBacKid]

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 ,  as long as the drug works!

[Ramjet]

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

[mark501]

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.

[ComeBacKid]

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

[Rico]

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

[mark501]

 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.  

[Rico]

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

[Tim468]

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

[Rico]

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

[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

[George999]

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!

[Rico]

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

[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

[George999]

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!

[Tim468]

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

[ComeBacKid]

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.

[Rico]

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

[ComeBacKid]

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

[Power]

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!!"

[George999]

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

[Tim468]

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

[ComeBacKid]

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

[George999]

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

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

[Rico]

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

[Tim468]

BTW, the DNA treatment described below was not done useing adenovirus, but a "plasmid" dna (think spare change in your pocket)

Tiu

[Rico]

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

[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

[mark501]

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".  

[George999]

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

[ComeBacKid]

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

[mark501]

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.

[ComeBacKid]

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

[Power]

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

[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

[mark501]

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.