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

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j

Xiaflex is just a trade name for collagenase. The "ase" suffix basically means "dissolves". It dissolves collagen. Many structures in your body are made of collagen, and there are different types of collagen. I believe Xiaflex targets one type; but that type also occurs in healthy tissue. So you can't just inject collagenase anywhere, the results could be very bad.  

For Dupuytren's, they inject Xiaflex into the interior of a cord, with the intent of dissolving enough of it - from the inside out - that it is weak enough to snap. The woman in the video described how the doctor let the collagenase work for a while,then pulled the finger straight, snapping the cord. They're trying to keep the action of the Xiaflex confined inside the unwanted Dupuytren's tissue.

There have also been some immune system reactions to the Xiaflex injections, causing inflammation.  

ocelot556

A few links, because sometimes a starving man can make do with the faintest whiff of food to get him through the hunger.

http://www.medscape.com/viewarticle/584669 -- this seems like a stretch, as they're identifying cardiac fibroblasts. But even if this exact drug has no Peyronies Disease applications, it's an exciting step into getting at the genetic triggers that cause fibrosis.

http://www.promedior.com/randd_SAP.html -- This is more long-term, but harnesses the bodies own cells to mediate fibrosis. As an aside, I think it's crazy that as a resident of SE Pennsylvania, both Xiaflex and this company are located in the town next to my office. If only I could go knocking on their doors with a fistful of cash for a quick hit of Peyronies Disease meds! :p

samsabina

Has anyone else been concerned about the apparent change in Neprinol formulation? A bunch of sites and people are claiming that Neprinol isn't really Neprinol anymore, and that you have to get something called Serracor-NK to get the original formulation that worked so well.

As in:
http://www.biomediclabs.com/systemic_enzymes
and
http://gentlehugs.wordpress.com/2009/06/17/why-did-i-switch-from-neprinol-to-serracor-nk/

Any thoughts on this? I couldn't find anyone talking about this on the forums.  

ohjb1

I have heard from someone at my urologist's office (though not confirmed) that there will definitely be a next phase of Xiaflex trials. Does anyone have any information about this?  

Maverick

I don't know where to post this seeing as the threads regarding Auxilium Pharmaceuticals have been locked. Basically I wanted to let people know that clinical trial of AA4500 is in its 2nd phase, with results expected in October of this year.
http://clinicaltrials.gov/ct2/show/NCT00755222?term=peyronie&rank=1

I don't know why those threads were locked, or why no one posted this crucial follow up yet. As I mentioned elsewhere, more needs to be done to raise awareness about this disease. This section of the forum is a good place to start.

For those interested, Baylor College of Medicine is recruiting participants for a Botox study on Peyronie.
http://clinicaltrials.gov/ct2/show/NCT00812838?term=peyronie&rank=2

Good luck.

j

Maverick, I think that trial is the one just completed, regarding which there have been a lot of posts.  We're all hoping that when the results are announced in Octrober that they'll be more positive than what one might conclude from what we've heard so far.


Botox? Sounds hokey to me.  Why would Botox have any effect on fibrosis?



cowboyfood

Quote from: j on August 04, 2009, 02:45:44 PM
We're all hoping that when the results are announced in Octrober that they'll be more positive than what one might conclude from what we've heard so far.


IMO, no need for anyone to conclude anything from the few posts made on this board in regards to their alleged participation in Auxilium's trial.

CF
Currently:  L-Arginine (2g), Vit D3)

jayhawk

What is the science or concept behind the use of botox for Peyronies?
Jayhawk

j

Quote from: jayhawk on August 04, 2009, 03:39:14 PM
What is the science or concept behind the use of botox for Peyronies?

My guess is the analysis went something like this:


1. Botox works by blocking nerve receptors for muscle fibers, thus paralyzing those muscles. If the muscle's contraction was causing a visible wrinkle, that wrinkle is reduced.

2. Most people don't really understand what Botox does, and think it just smooths things out, somehow.

3. Lots of people are making tons of money selling Botox injections.

4. They'd like to make tons more by selling it for other conditions, even if it doesn't work.

5. One way to accomplish #4 would be to do an actual clinical trial for Peyronie's, using fuzzy and misleading success criteria so the results can be easily "spun".

ohjb1

I have communicated with the physician in the Botox trial. It is his contention that inserting the needle into the plaque dislodges it to a certain extent and he hopes to prove that the Botox inhibits reformation of this plaque.  This does not seem likely to me, but who really knows at this point.  

skunkworks

Quote from: ocelot556 on July 02, 2009, 06:24:42 PM
Wow, George, that's an amazing find. Modern medicine is trying to "move up" in the command structure of the body, and it seems like this compound - if it works as advertised - will be doing just that.

Imagine, one teaspoon a day for a month and you can hit 'reset' on most major autoimmune disorders. It's good news for our affliction, but it's great news for people with MS, arthritis, and diabetes. Here's hoping it's all that little-known blog talks it up to be.

and psioriasis, hair loss, dermatitis, allergies, the list goes on.
This is an emotionally destructive condition, we all have it, let's be nice to each other.

Review of current treatment options by Levine and Sherer]

Maverick

Quote from: ohjb1 on August 04, 2009, 05:45:09 PM
I have communicated with the physician in the Botox trial. It is his contention that inserting the needle into the plaque dislodges it to a certain extent and he hopes to prove that the Botox inhibits reformation of this plaque.  This does not seem likely to me, but who really knows at this point.  

If that's the angle of the trial then the objective seems quite weak. Ultrasound would be far more effective in breaking apart plaque, and it reformation would be dependent on a person's immune system (which could be boosted with other drugs). A combo of ultrasound and Botox would be a step in the right direction for a clinical trial, but then there are two variables instead of one.  

George999

Peyronie's plaque is made up of collagen and bio-debris.  It is the consistency of leather and ultrasound is not going to have any effect on it no matter how powerful.  I'm not convinced that needle poking is going to do it any good either at least not over the longer term.  As for Botox, guys, its a TOXIN.  Hello!  I think perhaps what they are trying to do here is poison the plaque.  But I can assure you they won't be using my penis as a guinea pig.  - George

Woodman

I actually go to BCM Baylor College of Medicine where the doctor developed the Botox injections. My Urologist and the Doctor work in the same department. I asked my Uros PA about the trials. They are very tight lipped on the subject. If I remember correctly he told me they do not actually know what it will do until they have the trails going and see the results. He also went on to say that it was never tested on humans up to this point. He told me they believe that it might relax the scar tissue.

Iam going back on the 14th of August I will ask him for a recap and post what I find for you all. I just remember thinking like george999 Iam not going to let them use me for a guinea pig using Botox.

Woodman

ocelot556

I agree, Woodman!

I am reaching another point of desperation with this disease, being on the cusp of losing a relationship over my impotence, and even as wracked with emotions as I am I still can't bring myself to apply for the trials. I don't see any purpose to sticking your penis with botox. I wonder what kind of men would, or how desperate, especially since Xiaflex - which isn't a paralyzing toxin - is just around the corner?

Maverick

Quote from: George999 on August 04, 2009, 09:56:02 PM
Peyronie's plaque is made up of collagen and bio-debris.  It is the consistency of leather and ultrasound is not going to have any effect on it no matter how powerful.  I'm not convinced that needle poking is going to do it any good either at least not over the longer term.  As for Botox, guys, its a TOXIN.  Hello!  I think perhaps what they are trying to do here is poison the plaque.  But I can assure you they won't be using my penis as a guinea pig.  - George
Hi George. I'm curious as to why you say that ultrasound will not have any effect. Ultrasound can vary in intensity and power based on the application necessary. Focused ultrasound can break gall or kidney stones apart and has been used in medicine for years. Molecular vibration can just as easily break apart plaque or tissue. Have you seen the post of the article from the American Journal of Physical Medicine & Rehabilitation?
https://www.peyroniesforum.net/index.php/topic,68.msg3571.html#msg3571

George999

All I can say is that there is some reason that ultrasound hasn't gained any traction and I would guess that would be because other current approaches just work better.  There are a number of studies out there that tout one or another success in dealing with Peyronie's, but then you pick up comments from people who have actually used those methods and got no perceived benefit and you just wonder.  I prefer simple approaches like Pentox where the majority of people who try it actually feel they are benefiting from it.  But in the case of ultrasound, 1) I don't understand how it can work on soft tissue like plaque without also damaging healthy soft tissue and 2) The comments I see from people who have tried it are not encouraging.  And somehow I see the same rabbit trail with Botox.  But who knows?  Botox might be a dark horse that surprises all of us, but I'm not holding my breath.  But I have to admit, either of the above make more sense to me than acupuncture  AND I would be ecstatic if you could prove me wrong on ultrasound, so go for it!  - George

ocelot556

Well, what about calcified plaques? I assume the reason it's safe to use on gallstones and such is because the stones themselves are more dense than the surrounding tissue - thus, different frequencies needed to break them up that are harmful to the stones, but not to the surrounding tissue.

Couldn't that be the case with Peyronies Disease plaques? I agree about the point of "soft tissue", but if those plaques have calcified, they've got to be more dense than the surrounding tissue.

I agree with George on this one, simply because of the negative feedback that ultrasound has gotten. Even Thacker's Formula has people who claims it cured them - I haven't seen one person attribute ultrasound to their recovery in anything but pain (which, as we know, can be treated in a whole host of ways without having one degree of effect on bend/plaque size/ed).

George999

Quote from: ocelot556 on August 06, 2009, 03:53:23 PMWell, what about calcified plaques? I assume the reason it's safe to use on gallstones and such is because the stones themselves are more dense than the surrounding tissue - thus, different frequencies needed to break them up that are harmful to the stones, but not to the surrounding tissue.

OK, yes of course, that would work.  In the case of gallstones, the debris from the stones gets flushed out the duct.  In the case of Peyronie's the debris from the calcification goes ... where?  - George

slowandsteady

Quote from: ocelot556 on August 06, 2009, 03:53:23 PM
Well, what about calcified plaques?
If I had calcified plaques, I'd consider high dose vitamin K2-MK4, at 15mg/day up to 45mg/day (45 mg/day in three divided doses was safe in this study of Japanese women. This is considered a pharmalogical dose. Note that this is K2-MK4, not K2-MK7.

s&s

ocelot556

Good point, George - but if the plaque is broken up via ultrasound, wouldn't it immediately become more pliant? A la the Leriche technique, by creating space between the binding tissue, you can extend it? I agree, though, it would be difficult to remove all calcification from the site. Of course, perhaps if you could break the calcified plaque down enough that a chelating agent might be more effective?

Maverick

Haaa... this reads like a bunch to scientists working in a lab speculating what the big red button on the table does...
Ultrasound has many frequencies, power levels and hence applications. Focused high frequency high intensity ultrasound is the one used to break stones and has recently been used in treating/burning off fibroids in women (search for it on youtube) whereby the "focused" ultrasound directs the energy into one exact location, thereby creating enough energy at that location to essentially burn the tissue or break the stone. In regards to Peyronies Disease (rather potential Peyronies Disease application), the ultrasound used is not focused, and thereby creates vibrations over a larger surface area at the cellular/molecular level, stimulating tissue and increasing blood flow. Picture body tissue now, one side of which is softer and "healthier", and the other side which is harder and "unhealthier". Apply ultrasound at the invisible line where the two sides touch. Ultrasound creates vibrations so that this "line" starts to get blurred, and the blood flow from the healthy side starts to have openings and space where it can start getting into the unhealthy side and stimulating the area. The plaque being denser than the softer tissue, will actually be hit by more sound waves where since the cells are closer together, the waves are not able to pass right through. In the softer tissue where the blood flows freer amongst the cells, there is space amongst the cells to let the sound waves through.
That's a basic concept of ultrasound in regards to Peyronies Disease. Also, I'm not one to see the cup as half full, but I have yet to read on ultrasound therapy going wrong when applied to Peyronies Disease or other medically similar applications, so if anyone has concrete medical references or articles, please point me to them. I'm not saying this is a cure, I'm just wondering why more people don't try it.

George999

OK guys, I see where your coming from on this and, as I said before, I'd be delighted to be proven wrong.  I thoroughly agree that it should be investigated further.  Once again, the problem becomes finding the funding, thats the ditch we always seem to end up in.   :-\  - George

j

I think the term "plaque" just confuses things.  It implies some sort of hard deposit that needs to be "broken up".  And the term "calcified" suggests the mineral deposits in an old water pipe.  The reality is  - it's fibrosis, a tangle of collagen and fibrin molecules.  These are proteins - the same ones found in normal, healthy. connective tissue. It's not something brittle that might be shattered by ultrasound.

I've never really understood use of the term "calcified".  It's claimed that this tissue accumulates calcium over time but I have doubts abou the use of this word, too.

Those of us who also have Duputyren's contractures have a sort of sanity check to apply because Dupuytren's is the same thing in another area of the body - the tissue has been found to be virtually identical - and seems to be better understood than Peyronie's.  With Dupuytren's the term "plaque" is never used, no one talks about "breaking up" the plaque, and ultrasound is known to have no effect.  It's just fibrosis, period.  Dupuytren's tissue doesn't "calcify" either.  

Many things that have been suggested as treatments for Peyronie's have been tried for Dupuytren's years, or decades, ago and found not to work. Vitamin E, Potaba, various antioxidants, accupuncture, NSAIDs, antihistamines, and of course transdermal Verapamil are all ancient history in the Dupuytren's world, no longer even discussed.  All sorts of systemic meds have been tried and in the end, Xiaflex (collagenase) is the only one to show real effect, and attract investment.  Everything else has faded away.


newguy

I'm not sure that I totally agree with the previous message, but aside from that let's not forget about the inflammatory processes at work. All too often it's easy to look at peyronie's from the perspective of existing and often extensive fibrosis and so forth, but if future treatments are able to knock out the inflammatory processes very effectively and very fast, then for many men dealing with peyronie's may simply be a case of taking a short course of treatment to allow normal healing to take place.

I do hope that Xiaflex does hold a place to in teatment of long term sufferers of the condition though. Maybe in conbination with a wide ranging oral treatment regimen (to diminish reoccurence) and traction, thi could prove to be a urprisingly effective mix. The jury seems to be out of Xiaflex for peyronie's right now though.

Intead of saying that treatments don't work at all, maybe it's more accurate to say that they don't cure peyronie's.  

j

Dupuytren's also causes inflammation early on, which was the reason for trying NSAIDs and antiistamines.  I believe no one ever demonstrated success in stopping the eventual progression of the fibrosis, but that might be because no one tried hard enough.  To me though these "inflammatory phase" ideas remind me of all the things that are supposed to cure a cold if taken at the very earliest stage - i.e. by the time you're sure you have a cold, it's too late, they only "work" when there's a 50% chance you don't even have one.

Research on ways to prevent Peyronie's by intervening in the "inflammatory phase" seems unproductive to me because no one seeks treatment at that point.


newguy

Quote from: j on August 08, 2009, 04:00:22 PM

Research on ways to prevent Peyronie's by intervening in the "inflammatory phase" seems unproductive to me because no one seeks treatment at that point.


I'm more interested in the efforts of those trying out new strategies and oral treatment combinations to attempt to give hope to peyronie's sufferers. This all sounds a bit doom and gloom to me. If people are not seeking treatment during the inflamatory stage, then we should enlighten them to the possibility of doing so, rather than assume that little can be done to help the situation. Doing something is always better than doing nothing.

It seems likely to me that the most promising future treatments may well relate to altering the immune resource to inflammation as soon as humanly possible, which is why it's worth exploring options like LDN. There is no way of knowing when a breakthrough will come, but with a proactive approach there is hope that we will stumble upon something.  This in combination with treatments that are somewhat helpful (VED and so on), is a sensible approach to a difficult problem.  What's the alternative?

QuoteDupuytren's also causes inflammation early on, which was the reason for trying NSAIDs and antiistamines.  I believe no one ever demonstrated success in stopping the eventual progression of the fibrosis, but that might be because no one tried hard enough.

Used early on, radiation therapy appeared to be somewhat successful. I haven't checked out studies but on the forum there, people seem to be pleased with the results, so something positive appears to be happening: http://www.dupuytren-online.info/radiation_therapy.html  I'm not suggesting this as a treatment for peyronie's, but rather trying to push the idea that we need to muster the motivation to really go all out looking for new treatment strategies, and maintain hope for others even if our own situation isn't great in all cases.  

androman

Have you all seen this non surgical treatment for Peyronies Disease?

(link disabled)


Full disclosure.  I do represent this product as an affiliate.  If anyone has any questions or needs additional info, please email me at androman101@yahoo.com

They stand by this product and guarantee it 100% or your money back.

It is backed by scientific studies.  Please visit the site for full details, videos, testimonials, and clinical data.

I do not suffer from Peyronies Disease but I did use this product prior to becoming an affiliate and although it did not add the full 1.4 inches in length, it did add right at one inch in length.

newguy

Any new updates from those previously enrolled in the Xiaflex trials? We had something of a mixed bag before, with some people claiming improvement, or one that I can remember stating that his condition actually worsened.

My thoughts are:

- I wonder if the follow up they perform is sufficient. It's not beyond the realms of possibility that men could experience negative changes outside of the obervation period.

- As moderate brusing and swelling appear to have occured with some men (men prone to penile injuries escalating), maybe this can inhibit some potential improvement. Hopefully in combination with other treatments (oral, mechanical), this negative could be lessened. It stands to reason that getting on a good oral treatment routine early on in the peyronies lifecycle is useful, thus it would probably be a good idea for those undergoing xiaflex injections to do this too as a precaution. I suppose that's out of the question during the initial trials, but in the long run, it would make sense.

cowboyfood

Quote from: newguy on August 15, 2009, 09:11:36 PM
Any new updates from those previously enrolled in the Xiaflex trials? We had something of a mixed bag before, with some people claiming improvement, or one that I can remember stating that his condition actually worsened.



newguy,

I too appreciated the fact that some men took the time to post about their experience.

However, I'm infinitely more interested in the company's actual report than anecdotal stories from those claiming to be a part of the trial.  This is because many members will engage in mere speculation on the treatment's potential based on a forum post.  In fact, the self-alleged trial participants have to speculate themselves as to whether they even received Xiaflex as opposed to the placebo!

CF
Currently:  L-Arginine (2g), Vit D3)

newguy

"In fact, the self-alleged trial participants have to speculate themselves as to whether they even received Xiaflex as opposed to the placebo!"

Yes, that's very true. I guess we have to play a waiting game for now.

I notice that phase 3 trials for Xiaflex for Dupuytren's have resumed:  http://www.medicalnewstoday.com/articles/79922.php

ohjb1

There is a recent interview with Auxillium executives and I don't see much in the way of a discussion about a decrease in curvature due to Xiaflex.  Hope I am wrong, but this may be a bad sign.

http://seekingalpha.com/article/135832-auxilium-pharmaceuticals-inc-q1-2009-earnings-call-transcript?source=yahoo&page=10  

newguy

ohjb1 -

They are somewhat limited as to what they feel comfortable in stating. The previous results (in study A) revealed that a 25% reduction in curvature "was achieved at three and six months with 58% and 53% of patients, respectively". This to me is not exactly a resounding success, and surely the three and six month differences actually mean that some mens curvature initially improved, but then increased somewhat between that period (from the point of improvement, not the starting point - i don't want to scare people :)).

Not to put a total downer of it though, as it very much appear that the treatment program does play a large part in the success or otherwise of the treatment. Study B which effectively involved receiving more injections resulted in 25%+ improvement in 8 out of 9 patients. I'm unsure of whether modeling (via a traction device I assume?) was used in these phase IIb trials, though it was used in phase IIa. The comment regard it from Auxillium, well I couldn't quite figure out how it applied to the latest trials:

"The other piece that we are testing is whether or not modeling works or doesn't work. One of the studies had modeling, the other one didn't. The one that had modeling in the previous IIa had somewhat higher and a more sustained effect, but we are testing that at this particular point in the trial."

Auxilium did note that " the FDA, in our discussions with them prior to the initiation of this trial, really encouraged us to go down the pathway of developing the patient reported outcomes, because they believe that a greater than 25% reduction in angle, if it doesn't translate into meaningful improvement in sexual activity, reduction in pain, and some of the other domains, probably isn't a valid objective endpoint.". This suggests that there are doubts over whether a 25%+ improvement is enough to make this worthwhile. Hopefully they will decide that it is worthwhile.

Phase 3 trials could be happening next year. If the improvement was, say 50% I think that would be reason to be really happy about all of this. If it does make it to markey though, use of Xiaflex in combination with other treatments could still make the difference to an awful lot of men. Time will tell how this pans out.

ohjb1

Thanks for your reply. Just a few follow up comments. I was in the phase IIb trial and was in the modeling group. Secondly, everyone in phase 11b who received Xiaflex as opposed to the placebo received the same dosing as those in the previous trial who reported 8 out of 9 participants who improved. Of course, we do not know who received the placebo and we are speculating.  FYI - There has been no change in my condition.  

newguy

Are you aware of many other men is the study and how their condition fared after the treatment? Are you under the impression that you received a placebo, or xiaflex? Of course it's of limited use to discuss these things when compared to the released results, but it's of interest to speak to someone who went through the process.

ohjb1

Newguy - don't know anything more about other men other than what I read on this forum. One member contacted my privately and also said no change in his condition after the trial.  Whether i received Xiaflex or placebo, really don't know. Some forum members believe that if there was bruising they recevied the real thing. My urologist said this is not the case as the insertion of the needle into the plaque results in bruising.  Basically, we are in the dark until the results of published.  

j

The treatment probably wasn't agressive enough.  

For Dupuytren's they injected Xiaflex, let it work for a while to weaken the tissue, then tried to forcibly straighten the finger and snap the cord.  And I mean "forcibly".  The injection of Xiaflex on its own wasn't powerful enough to simply dissolve the cord and release the finger. They're afraid that if they injected enough Xiaflex to do the job on its own, there'd be collateral damage to surrounding "good" tissue.

With Peyronie's they're dealing with a more delicate structure and so I think they were even more conservative. As a result they didn't break up enough tissue, in most cases, to cause a truly useful change.  

This was probably not a surprise to Auxilium. To get FDA approval you need to show complete safety but only very modest positive effect.  This is why we often end up with widely prescribed big-name drugs that really aren't very effective, and sometimes long term followup studies show that they're a waste of money.  Once FDA approval is secured, a drug company may stop spending money on additional research and just pour it into massive advertising campaigns.  I hope that doesn't happen here, and that Auxilium works on improving the effectiveness of Xiaflex treatment.  

This forum can have a real impact on what Auxilium decides to do.  

skunkworks

Hmm so would you say that the treatment should involve an injection of xiaflex and then something to give and maintain an erection for awhile, so the xiaflex weakens the fibrotic tissue and the erection remodels the shape?
This is an emotionally destructive condition, we all have it, let's be nice to each other.

Review of current treatment options by Levine and Sherer]

j

Maybe more injections over a wider area; maybe in combination with a stretching device or VED;  maybe several treatments over a period of time.   I don't want to speculate too much further because I'm not a doctor.  

With Dupuytren's the corrective treatment can get pretty rough. With Peyronie's, a more sophisticated approach will be required.


ComeBacKid

I just talked with a doctor friend of mine in regards to these trials.  He stated to me that the FDA is more concerned with safety as J has already stated.  They are probably overly concerned about this in my friends opinion, however they due it to protect potential patients.  They are less concerned about effectiveness, once they get the clearness I think as J states there will be a much more aggressive treatment protocol.  Really it could be many things.  I'm looking forward to seeing some ultra sound evidence that the drug can really dissolve the peyronies plaque or tissue or modify it.  VED could be used to help stretch the tissue if it is only made to be more flexible but not completely dissolved.  

J is right in that this forum can have an impact on what this forum does.  It is extremely important that we continue to work hard to grow our membership, as we are doing in the advocacy section of our forum, anyone who is interested come take a look, we are working on a  mass mailing project to urologists to recruit more peyronies sufferers.  We need to grow our membership, and at some point write a letter to Auxillium or leading urologists who have pull.  J is absolutely right in that it is important once Auxillium gets the FDA safety clearance, they don't stop working on the effectiveness of this drug, otherwise we may not get the full cure we are looking and praying for here.

Comebackid


j

In the Dupuytren's trials, they had a couple cases of tendon damage:
 http://tinyurl.com/mh95ux

The article at that link includes comments from a couple of hand surgeons who in my opinion are overly negative.  I've had Dupuytren's surgery - it's rough, damage can happen (I had a nerve severed),  recovery is long, infection is possible, scar tissue builds up - and surgeons tend to minimize all these risks.   Many people feel that hand surgeons simply don't want to lose the income from Dupuytren's sugeries.  I won't go that far, but I think they're instinctively resisting a non-surgical alternative.  The surgeons quoted in this article do make a good point, which is that injecting Xiaflex requires a detailed knowledge of the target anatomy.

Xiaflex is potent stuff, biologically active - unlike all the snake oil we've been sold in the past - so some issues are to be expected.  

ComeBacKid

J,

It could be possible doctors would resist a solution, as then they couldn't do surgeries and make $$$, since they get paid significant money based on procedures.  However they'd have to be in bed with Auxillium wouldn't they?  Wouldn't auxillium purposely have to be sabatoging their own product  in xiaflex?

Comebackid

j

I'm not much into conspiracy theories.  I'd just say that surgeons seem to be very conservative and not open to new ideas unless they come down from above, through the usual channels.  Surgeons want to do surgery - it's what they know.   Some, maybe most, of them also want the best deal for their patients.  

The surgeons probably know how complex and variable the human anatomy really is - they see it from the inside - and they don't like the idea of some Beverly Hills MD adding to his Botox income by injecting Xiaflex and letting the lawyers deal with the mistakes. But in my experience, surgeons minimize the risks and downside of their own procedures.

Reading this article, I can see how urologists might be cautious about getting into this treatment.  




ComeBacKid

Hey guys,

Saw this in the usa today, just found it interesting since we know phizer bought auxilium out and the right to market their drugs.

Phizer gets fined big time!

Wow, thats a heck of a fine to pay, I wonder if that will negatively effect the company's ability to market or develop future drugs like xiaflex?

I was reading up on off-label usage, I did not know it is legal to prescribe medications for off-label usage, but illegal to market them.  So really anyone in this forum who is taking pentox for peyronies is using an drug for an "off-label" purpose.

Off-label use is the practice of prescribing pharmaceuticals for a purpose outside the scope of a drug's approved label - an unproven, untested use - most often concerning the drug's indication[citation needed]. In the United States, the Food and Drug Administration (FDA) requires numerous clinical trials to prove a drug's safety and efficacy in treating a given disease or condition[citation needed]. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route and other information to be included on the drug's label. More detail is included in the drug's package insert.

However, once the FDA approves a drug for prescription use, they do not attempt to regulate the usage of the medicine, and so the physician makes decisions based on her or his best judgment. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off-label, including controlled substances such as opiates. Actiq, for example, is commonly prescribed off-label even though it is a Schedule II controlled substance. However, it is unlawful to market, advertise or otherwise promote the off-label use of drugs, including controlled substances.

Off-label use of medications is very common. Up to one-fifth of all drugs are prescribed off-label and amongst psychiatric drugs, off-label use rises to 31% (Radley, et al. 2006).[1] New drugs are often not tested for safety and efficacy specifically in children. Therefore, it is believed that 50-75% of all medications prescribed by pediatricians in the U.S. are for off-label applications.[2]

Some drugs are used more frequently off-label than for their original, FDA-approved indications. A 1991 study by the U.S. General Accounting Office found that one-third of all drug administrations to cancer patients were off-label, and more than half of cancer patients received at least one drug for an off-label indication. A 1997 survey of 200 cancer doctors by the American Enterprise Institute and the American Cancer Society found that 60% of them prescribed drugs off-label. [3]. Frequently, the standard of care for a particular type or stage of cancer involves the off-label use of one or more drugs. An example is the use of tricyclic antidepressants to treat neuropathic pain. This old class of antidepressants is now rarely used for clinical depression due to side effects, but the tricyclics are often effective for treating pain.


Off-label  use





newguy

QuoteInjectable Collagenase Clostridium Histolyticum for Dupuytren's Contracture

Methods We enrolled 308 patients with joint contractures of 20 degrees or more in this prospective, randomized, double-blind, placebo-controlled, multicenter trial. The primary metacarpophalangeal or proximal interphalangeal joints of these patients were randomly assigned to receive up to three injections of collagenase clostridium histolyticum (at a dose of 0.58 mg per injection) or placebo in the contracted collagen cord at 30-day intervals. One day after injection, the joints were manipulated. The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection. Twenty-six secondary end points were evaluated, and data on adverse events were collected.

Results Collagenase treatment significantly improved outcomes. More cords that were injected with collagenase than cords injected with placebo met the primary end point (64.0% vs. 6.8%, P<0.001), as well as all secondary end points (P0.002). Overall, the range of motion in the joints was significantly improved after injection with collagenase as compared with placebo (from 43.9 to 80.7 degrees vs. from 45.3 to 49.5 degrees, P<0.001). The most commonly reported adverse events were localized swelling, pain, bruising, pruritus, and transient regional lymph-node enlargement and tenderness. Three treatment-related serious adverse events were reported: two tendon ruptures and one case of complex regional pain syndrome. No significant changes in flexion or grip strength, no systemic allergic reactions, and no nerve injuries were observed.

Conclusions Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren's disease. - http://nejm.highwire.org/cgi/content/abstract/361/10/968

Of course peyronie's only has a limited amount of common with Dupuytren's (it would probably be unwise to attempt to manipulate the penis in the same way you'd manipulate a joint - other than by light traction) . That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less.

ComeBacKid

That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less

Newguy, what peyronies results with xiaflex are you referring to, I thought that auxilium has not published any results yet unless I missed something?  ???


newguy

ComebackKid - I was refering to the info out there thus far, and not any new results. I look forward to us receiving any updates relating to how effective this treatment actually is.

cowboyfood

Quote from: newguy on September 04, 2009, 07:05:07 AM

That being the case the peyronie's results with xiaflex are of course not as impressive, but this study interesting none the less.


Newguy,

with all due respect (you're one of my favorite posters), your statement (see above, emphasis supplied by me) is conclusionary and is not supported by any cited sources.

I believe you may be referring to a conference call provided to primarily the investment community, and if I recall, the company did not publicly reach the conclusion that you have.  Or, even less authoritative, posters alleging to have participated in the trials.

Another point (and, I may be way off base here), regarding drug research on trial participants, the actual participant results that "we" may conclude are not "impressive" may in fact be of invaluable information to the researchers.  Meaning, the results provide them with information that they can use to "optimize" the drugs use.

So, although I appreciate your interest in the Xiaflex trials, I cannot agree with your above statement and it may cause other readers to become disillusioned.

thanks for all your efforts!

CF
Currently:  L-Arginine (2g), Vit D3)

newguy

Hi cowboyfood. My comments are based on the reduction of most of the joint contractures in dupuytren's patients to between 0-5 degrees. The early clinical trial results for peyronie's revealed a 25%+ reduction in curvature. It may be the case that some of those improvements were very significant, or that the technique can to has been refined to maximise the potential of xiaflex, so I would not wish for anybody to be disillusioned. Should the treatment become available to us all at some stage, and ill effects or complications are minimal, maybe it will be possible to successfully combine it with other treatments or have further injections. I'm as much in the dark as anybody really and hope that future announcements from auxilium.com are promosing.

Strictly speaking the effectivness of the dupuytren's trials are as probably as much to do with the nature of the condition (that once the the scar tissue is sufficiently weakened it can be totally released from the underlying tissue), which differs from that of peyronie's disease. Again, Xiaflex may potentially offer an almost instant reduction in curvature for many individuals, so I don't want to put a downer on it. It's certainly a treatment of interest.

Thanks for your posts too :). I really don't mind people disagreeing with what I write, as its healthy to have ideas challanged and to be corrected if I make statements that cannot be 100% backed up.

j

Quote from: newguy on September 05, 2009, 05:40:37 PM
Strictly speaking the effectivness of the dupuytren's trials are as probably as much to do with the nature of the condition (that once the the scar tissue is sufficiently weakened it can be totally released from the underlying tissue)...

That's partially true. Dupuytren's contractures may or may not be strongly adhered to the surrounding tissue.  When there is a lot of adhesion the contracture can only be released by surgery, and that may be only partially successfull.  Contractures in the palm tend to have much less adhesion, and be easier to release by 'snapping', than contractures further out in the fingers.