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

[mark501]

Jan 7th 2008 from Auxilium Pharmaceuticals: to Securities & Exchange Commission: "In life stage of animal study (outside of plaque) completed 4th quarter 2007. Expect to send final report to FDA 1st half 2008. Phase IIb dose ranging study (clinical trial) expected 2d quarter 2008 pending FDA review of animal study.

[j]

Still years away....

However I recently read a stock analyst's writeup on Auxilium. He said that to meet projections (stock price, earnings), they will need to market Xiaflex for Peyronie's.  The Dupuytren's market alone won't do it.  So there there may be strong financial incentives for them to actually finish the work on this.

[pal-31]

Well, I was at my Uro yesterday and he said that if FDA approves, the trials could start in a couple of months. Who knows how long the trials will be and when will the final results come out, but if it is approved for DC who knows may be there will be off-label use.

BTW, I was looking at the a DC forum the other day and found a thread about it where people saying they had success with it and it restored function to their hands.

Regards,
Pal

[bodoo2u]

Am I to understand that Xiaflew will not reduce curvature, but will make intercourse possible by making the plaque fexlible? Is that the idea?

[mark501]

Pal-31, I understand that at least one protocol for trial IIb will be 6 injections over a period of 13 weeks. Mark 501

[roadblock]

Is there anybody reading this forum that has received any of the trial injections of Xiaflex? I'm sure all of us would be interested to hear how these individuals are doing now several months out from their treatment!

[pal-31]

Bodoo2u,

Actually the trials they had on Xiaflex only measured the curve. They defined success as a decrease of greater than 25% of the angle of the curve. I don't think they measured other symptoms and they are probably right to focus only on the angle as it is measurable. Other parameters may be harder to measure and could get into the subjective realm.

However they did give each participant a questionair that asks about other things.

This was from a presentation I read on their web-site about the medication. It was a long presentation but very informative.

Pal

[Liam]

They have been measuing the size of tumors for many years.  I am more than a little suspicious about the reason they are not measuring plaque size.  They obviously don't hold out any hope it will destroy plaque.

As far as 25%, that is not much considering all the hype.

[mark501]

The questionaire to be filled out by participants in Xiaflex clinical trials will be similar to the one used when Viagra was in clinical trials. The questionaire for Viagra trials was one element considered by the FDA in making its final approval and the same applies to Xiaflex.  

[pal-31]

Liam,

I really hope it is not so. However, I also happened to stumble on a DC forum and people there was reporting good results. The Auxiliam presentation said the results showed, if I remember correctly, something like 80% say they "greatly improved" or improved. At least that tells me it is better than Verapamil which if we polled 10 people who used it we will probably find 5 that say they were worse or much worse as a result :-)

I agree the jury is still out but we can only hope ( and pray)

Pal

[j]

I have Dupuytren's and have been following that situation in detail.  Xiaflex definitely works. In the trial, they simply used it to weaken the cord until it could be forcibly snapped by the MD - he literally gets a good grip on your finger and straightens it until the cord breaks, often with an audible 'pop'.   There's been some soreness and bruising but nothing major. However, the treatment for Peyronies will obviously have to be a bit less direct.  Multiple injections over a period of time should cause some breakup of the collagen, but who knows how much and what the effect will be.  It will probably vary a lot.

Even if it works, Auxilium isn't going to produce it unless they can make what they feel is an appropriate profit.  After all these years of speculation and hype, that means they intend to charge a heckuva lot of money and if they can't get it, AUXL stock - which has had a big runup - will be seen as overpriced and existing options might be underwater.

Quote from a stock analyst:  "If Xiaflex is to succeed, Auxilium will need to displace surgical procedures and convince insurers to pay the same for the drug as the surgery. Surgery for Dupuytren's costs $5,000. For Peyronie's, the price is $11,000. CEO Anido figures Xiaflex would bring similar prices."

[couldbeworse]

I would gladly pay $11,000 for a few injections of collagenase to fix this problem.  Curious to find what others might pay ...

BTW, if you'd invested $3000 in AUXL when it sold for $8/share (not long ago), the value of your stock would now pay for your treatment.

[ocelot556]

11,000!? That stinks. I'm just out of college, that's about half of a yearly starting salary, give or take a few grand, and not considering any other expense. I wonder if the healthcare people will cover it - or, since it's useful and desirable they'll label it "experimental" and refuse to cover.

That is so disheartening. I know medical procedures are expensive, but when I read things from Auxilium that states things like "High motivated consumer base willing to pay for treatment" it just reminds me that most development is driven by accounting jackals and not medical practioners wanting to cure disease. You'd figure Auxilium, requiring much less invasive treatment than surgery and thus less skill required, would cost the patient LESS, not similar or more.

Anyway, just charging at windmills here. Let's hope insurers agree to pay. Money makes the world go 'round.

Jackp, you seem to know more about accounting than I (I'm an English Lit geek, no mathematical braincells in my head) -- if AUXL stock tanked, wouldn't that be beneficial for the poor patient? They'd try to cover the loss by selling the patented formula, perhaps? I can't beleive that they'd just let it fall into the dustbin of history if they didn't meet stock price.

[pal-31]

I dont think we should sweat the cost yet. First lets hope it works well for Peyronies and it gets approved. As for the money, and I am totaly guessing here, I dont think it will be that much as it will prevent many people from getting the treatment and the insurance wont pay. It will make more sense for them to price it where most patients can get it and the insurance wont fight it.

Just my 0.02$

[mark501]

In the Phase II trials with a small number of participants almost all had at least an improvement of 25 percent in their curvature. If I remember correctly there was one guy that had a 24 percent improvement. Auxilium did NOT reveal how many participants had an improvement more than 25 percent. Future trials will have many more enrolled and give a much better idea about the degree of effectiveness.

[bodoo2u]

Where do you guys find the information in Xiaflex trial results?

[Tim468]

For those of us with active disease (and I believe that is actually most of us), my concern is that even a "fix" will be just temporary, and that the disease will return. Of course, if I was fixed for a year or two, I'd gladly take it...

Tim

[Hawk]

For those of us with active disease (and I believe that is actually most of us), my concern is that even a "fix" will be just temporary, and that the disease will return. Of course, if I was fixed for a year or two, I'd gladly take it...
Tim

At $11,000.00 dollars a year I would almost feel obligated to have sexual partners lined up in my hallway to assure I got my moneys worth.

[j]

That figure, of course, is just a number thrown out by a CEO to reassure the board and the big investors that this grand "play" is going to pay off big.

Here's another analyst quote:
"The future of Auxilium relies heavily on the development of Xiaflex. [...] Upside to our Xiaflex forecasts could come from positive development in Peyronies Disease or Frozen Shoulder Syndrome.'We model Auxilium reaching profitability in 2011. The stock looks expensive at this level based on future earnings and the current price/sales ratio."

What this means is that financial success now depends on selling Xiaflex at a breathtakingly high price.  Doing that requires a big and very expensive sales/marketing effort, with lots of wining-and-dining of decision-makers.  If Auxilium ultimately can't get the insurance companies to pay, things get shaky because of all the cash being burned.  Executives see stock options evaporating and demand big bonuses instead, further draining cash. The board gets nervous and replaces top people - writing out big severance checks. New "rainmakers" come in based on unrealistic projections, then bail out with golden parachutes after 9 months.  Eventually - even with a viable product - there's no cash to continue, and no new investors coming in, and the lights go out. I've seen it all from the inside.

Iit might all work out, somehow.  Auxilium and the big insurers may settle on some figure that allows it to happen. Or, AUXL may flame out and the rights to injectable Collagenase are sold - once again - and we start all over...

I think success depends in large part on urologists agreeing to give this product a serious try, instead of referring us across town to their HMO's surgical group, or writing prescriptions for Topical Verapamil.

[pal-31]

J

Thanks for the insightfull information , that is a very interesting post. It is sad but I think it is true.

However, I remain optimistic in the Xiaflex case. I think this is the only drug so far that has shown consistent results. Also, it actually works for DC and other fibrotic conditions. Dr. Jordan is actually involved with these trials.

I think Auxilium is close to start making money on this so I dont think they will bail. I could be wrong on all counts, but I'd rather stay positive and hopefull which at least is good for my Peyronies Disease :-)

Thanks again,
Pal

[j]

There's nothing wrong with being optimistic. Number one, Xiaflex works against Peyronie's - that much has already been proven.  Number two, the company that owns the drug is actively trying to get it to market - in contrast to countless other usefull drugs for which speculators are sitting on the rights.  

Number three, this is sort of the way our world works.  Many other new drugs have passed through this gantlet of greed and bureaucracy, Xiaflex might make it too.

[ocelot556]

Why would speculators sit on a drug anyway? I know this is off topic, but what would be the point of sitting on a drug and not letting it get out to market? It seems like it's the difference between projected money, which gives only imagined gains in the future - and actual money, which one makes by selling a product.

I thought that the business world was about always selling. Sell, sell, sell. Not sit on something and not sell it in the hopes that one day you can.

[j]

The price of a stock is based mostly on "expected future value".  While a product is just a rainbow on the horizon, investment dollars pour in - based on nothing but hype - from investors who want in on the ground floor.   A successful round of fund-raising puts a lot of money in the bank which is immediately available for salaries and bonuses.  And this can go on for a long time.  But when a product actually gets manufactured and sold, it's real profitability becomes known, costs are incurred and the stock may plateau - often, the gravy days are over for the guys at the top.  

Sometimes the rights to a "promising new drug" are more useful as bait for investment than as the basis for a real product, which may never live up to its profitability projections. Sometimes, if a company is going under because of negative cash flow, selling a patent - rather than developing it into a product - is a quick way to raise money.

The patent on Collagenase has brought in many millions of investment dollars over the last 10 years.  The trials have been on, off, on, off more times than I can recall.  This time it looks like they're going to complete the trials, more than 10 years after collagenase was first used successfully on Dupuytren's..  

[mark501]

Biospecifics Technologies Corporation has a development & license agreement with Auxilium Pharmaceuticals for clinical applications of Xiaflex in treatment of Peyronies, Dupuytrens & Adhesive Capsulitis (frozen shoulder syndrome). Auxilium has an option to acquire from Biospecifics additional licenses for treatment of cellulite & lipomas. This from Biospecifics: " Significant portion of our revenues are tied directly to the success of Auxililum commercializing Xiaflex".

[mark501]

From Auxilium today: Urologists have reported to Auxilium that there has been an increase of patients seeking help with peyronie's since the introduction of PDE inhibitors. They further state that approx. 475,000 men with peyronie's consult with a urologist annually. The latest estimate of the cost of Xiaflex is $l,600 per each injection. They have patent protection until 2019.  

[j]

So if all those guys with Peyronie's get just one shot of Xiaflex, Auxilium grosses $760,000,000.  I'm sure the investors are loving these projections. But let's wait and see what the insurance companies say.  

[pal-31]

J,

We can have fun with these numbers. For a 16 injection protocol, which showed the most result, the total $$$ would be 760 M x 16. If this number of patients is only in the US then we could probably multiply that by 100 for world wide distribution, etc...

Auxillium needs to get busy and get this thing on the market so they can start making the big bucks...

Pal

[mark501]

Pal-3l, There is no 16 injection protocol. Previous trials for peyronie's had as many as 9 injections. The next trials, Phase IIb is a dosage trial in an attempt to reduce the required number of injections down to 6. In trials for Dupuytrens some patients only needed 1 injection per joint & some needed 2 but not more than 3.  I suspect that not all cases of peyronie's will require the same amount of injections for a good outcome.  Also I don't think that all men with peyronie's will be good candidates for this treatment. Auxilium is promoting the idea that they will become a billion dollar business.

[j]

Auxilium's investor pitch is probably something like this:

1.  The current treatment for Peyronie's is surgery.
2.  Insurance companies will pay for our treatment if it costs a little less than surgery.
3.  Surgery costs $11,000.
4.  Success is defined as a measureable reduction in curve, say 10%
5.  Our product is "successful" with an average of 6 injections.
6.  6 x $1600 = $9600

This leaves $1400 for 6 visits to the urologist.

It's all hype at this point.  The insurance companies may bring things into reality, or shoot down this product entirely. Maybe a long slow 'trial' period including pointless and unscientific self-evaulation of "customer satisfaction".  Or maybe it works great and within a couple of years, a lot of us are much better off.  Life is unpredictable.

[pal-31]

Mark,

I dont know where I got the 16 injections number from. I must have been half asleep. The number that got the most success was what they call group B which had 3 series of 3 injections so a total of 9.

Just from reading the results of the trials I am optimistic. Hopefully it will work for us. I am an average guy financially, but I would not mind paying the money if it worked as they claim.

Once it gets to market will find out (soon enough hopefully)

Pal

[Tim468]

If it works, believe me, we will all work all the angles to get it covered by insurance. For my insurance, I think that if I have a lot of pain with erections, surgery is covered, otherwise it's just "cosmetic".

Already, I think I feel an ache....


Tim

[Steve]

  Oh the Pain...The severe ED...The Loss of Appetite...The Dandruff...Anything to get Insurance to pay for it!!!

[j]

Mental health coverage is politically hot - insurers are under pressure. So - would it be more cost-effective to send me to a therapist until I accept that life with a bent peter isn't all that bad - or to pay 11K and maybe fix the problem?

Actually, the therapy is not going to be effective if I know there's an actual treatment.

[mark501]

How do you guys feel about being part of a clinical trial of Xiaflex if the cost of the medicine to you is zero? Would you be willing to pay for travel & hotel expenses if trials were held in another city? What if there was a possibility that you might receive a placebo instead of xiaflex? I have been weighing these questions and can't quite decide. Does an "open label" trial mean that there are no placebos involved?  

[pal-31]

Mark,

I am guessing that "open label" means you are getting the the real deal. Double blind usually means , I am guessing again, you dont know if you are getting placebo or the real stuff.

Are you being asked to participate in the trials ?

Thanks,
Pal

[j]

mark501, my understanding also is that no one will get a placebo.  

[Hawk]

I don't think you can ethically make multiple injections into a man's penis with a placebo.  You could possibly use a control like Verapamil, but I am not suggesting that they intend to use such a control.

[ocelot556]

I don't mean to beat a dead horse, but since the discussion was still revolving around money:

Is there any chance that, a few years out of the gate, Auxilium gets that initial "rush" of men waiting for Xiaflex and then drops thier price to lure in the less drastic cases of Peyronies Disease, the one's guys want to correct but isn't causing them ED or anything?

Similarly, what are the odds of insurers picking this up? I admit I know little to nothing of how they work, and given that I'm fresh out of college I'd be more likely to stumble on a chest of gold dubloons to pay for Xiaflex than find an employer willing to give me premium benfits. Don't insurers label anything they want as "new" or "experimental" and deny payments for them?

My only reassurance here is that insurers pay for Viagra, which isn't life-threatening but apparently important enough to warrant coverage. It seems that if getting hard is covered, straightening your penis would be an easy choice to cover.

[Hawk]

Don't insurers label anything they want as "new" or "experimental" and deny payments for them?

My only reassurance here is that insurers pay for Viagra, which isn't life-threatening but apparently important enough to warrant coverage. It seems that if getting hard is covered, straightening your penis would be an easy choice to cover.

I will comment only on your this quote.  I have Blue Cross and it does NOT cover Viagra.  I do get some kind of "discount that lowers the price somewhat but I still pay about $11.00 a pill for 100mg.  Also, insurance companies do not just get to label anything they want as experimental.  There are guidelines that establish what is usual and customary in the way of charges and to establish what is or is not accepted as standard treatment.

[j]

ocelot556, don't let all this cynical pseudo-analysis get you down.  

Any company starts out crowing about they'll get absolute top dollar for their whiz-bang new product, because the world will beat a path to their door.  And then they encounter reality.  If Xiaflex really works, and their really are that many guys with Peyronies, market forces will work to extract every possible dollar from everyone who might possibly pay.  Sometimes that means a product initially sells for a very high price to people who are standing in line with fistfulls of money; and eventually, the price sinks down and deals are worked out so they can collect money from the rest of us too.

Remember how fast the iPhone went from $600 to $400?

[jackp]

Hawk
I am a retiered county government employee. The powers that be have reneged on a verbal agreement and put us on Medicare Part D with a supplement.
None of the ED drugs are now covered and we have to pay full price.
Another case of the government taking money out of the pocket of retires to pay for there mistakes.
Jackp

[ocelot556]

Yeah, you're right. But since it's my opinion that a bad and barely-documented side effect from another drug caused my Peyronies Disease in the first place, and my own experience working for medical device companies, it hasn't left me with much love or trust of corporations in general when they're in the business of medicine. And Peyronies Disease is enough to make anyone a cynic! Hah.

[George999]

WASHINGTON, Feb 15 (Reuters) - U.S. health regulators on Friday issued proposed guidelines that would make it easier for pharmaceutical companies to advise doctors about unapproved uses for their drugs.

http://www.reuters.com/article/companyNews/idUSN1560771720080215

[jmaxx]

Hi,

Can someone recomend a doctor in the Chicago area, other than Dr Levine.  

I would like to locate a doctor who is working with the new Auxillum Xiaflex treatment.  

In the discussion form here: Peyronie's Advocacy Group - Awareness/Advocacy/Activism > Auxilium Follow Up

someone mentioned twenty doctors are participating in the Auxilium trials.  Does someone have a list of who those

twenty doctors are?

Thank you
JXYZ

[Hawk]

Jxyz,

I admittedly do not follow Xiaflex that closely, but I know of no doctors currently part of a trail of xiaflex for Peyronies Disease.  If there were any in the Chicago area, I think it is safe to say Dr. Levine would be one of them both due to his medical emphasis and his loose association with Auxilliam.  

[jsotheby]

Does anyone know whether the gene therapy being tested by Mehlman and Co. in New York would apply to cases of ed that might be caused by diffuse fibrosis or cavernosal scarring?

[George999]

Since I do not see this study posted anywhere, I am going to throw it out to you all now for any information you might glean from it:

The use of intralesional clostridial collagenase injection therapy for Peyronie's disease: a prospective, single-center, non-placebo-controlled study.
Jordan GH.

Department of Urology, Eastern Virginia Medical School, Norfolk, VA, USA. ghjordan@sentara.com

INTRODUCTION: Peyronie's disease afflicts at least 3% of sexually active men over the age of 30. Many pharmacologic therapies have been tried, but to date, no systemic or local therapy has been proven to provide predictable and lasting results. AIM: This study was designed to assess the efficacy and safety of intralesional clostridial collagenase injection therapy in a series of patients with Peyronie's disease. METHODS: Twenty-five patients aged 21-75 years who were referred to a single institution with a well-defined Peyronie's disease plaque were treated with three intralesional injections of clostridial collagenase 10,000 units in a small volume (0.25 cm(3) per injection) administered over 7-10 days, with a repeat treatment (i.e., three injections of collagenase 10,000 units/25 cm(3) injection over 7-10 days) at 3 months. Primary efficacy measures were changes from baseline in the deviation angle and plaque size. Secondary efficacy end points were patient responses to a Peyronie's disease questionnaire and improvement according to the investigators' global evaluation of change. MAIN OUTCOME MEASURE: The primary efficacy measures were change in deviation angle and change in plaque size. Secondary end points were patient questionnaire responses and improvement according to the investigators' global evaluation of change. RESULTS: Significant decreases from baseline were achieved in the mean deviation angle at months 3 (P = 0.0001) and 6 (P = 0.0012), plaque width at months 3 (P = 0.0052), 6 (P = 0.0239), and 9 (P = 0.0484), and plaque length at months 3 (P = 0.0018) and 6 (P = 0.0483). More than 50% of patients in this series considered themselves "very much improved" or "much improved" at all time points in the study, and the drug was generally well tolerated. CONCLUSION: The benefits of intralesional clostridial collagenase injections in this trial lend support to prior studies supporting its use in the management of Peyronie's disease. A double-blind, placebo-controlled study is currently under development.

PMID: 18173766 [PubMed - in process]

[Tim468]

Can't get hold of the whole thing. It is also another unblinded study, but supports the notion that breaking up scar made of excessive or abnormal collagen will relax the contraction. If one had a palpable plaque, I think it sounds very promising (and clostridial collegenase is not a "new" drug, and coult herefore be studied but not have to go through the same FDA hoops as a new drug).

Tim

[roadblock]

George999, that study you posted I believe is the abstract for the Phase II study done by Auxilium for Xiaflex, right?

With regards to Xiaflex, I was thinking that one way in which this forum might be helpful to its members would be for everyone who sees a urologist to ask them (the urologists) whether they are familiar with the clostridial collagenase studies and if they will be using this drug off-label for peyronies once it is approved for dupuytren's. It may cause them to research it more and possibly incorporate this therapy into their practice if they feel it safe and efficacious. Everything I have read thus far has been positive and although no definitive studies have been completed they are in the works. Although it will be no magic bullet, it seems that this will be the best option yet for non-surgical management of this disease.

So, next time any of you go to your urologist ask about Xiaflex (clostridial collagenase) and see what they have heard and if they plan to be using that off-label because it is becoming more and more acceptable to do so when it seems appropriate. I would guess that at least a handful of urologists across the country will be doing so and I'm sure many of us will be lining up for an appointment! It's not to early to begin to discuss this because the data from the dupuytren's study should be out shortly and they anticipate applying for a patent I believe by this time next year.

roadblock

[Tim468]

Ah, I think that Roadblock has it right. This is Xiaflex.

Tim