Xiaflex - one more step towards use with Peyronie's

Years away for use with penile fibrosis, but still worth following...

Triumph for Xiaflex, Drug to Straighten Clenched Fingers - NYTimes.com

... The Food and Drug Administration approved ... Xiaflex, last month as a nonsurgical treatment for Dupuytren’s contracture, a condition in which one or more fingers cannot be straightened.

Xiaflex, an injectable drug that goes on sale later this month, will not be cheap, at an estimated average cost per course of treatment of $5,400. But analysts expect sales to reach hundreds of millions of dollars a year.

And that total could go higher, if Xiaflex eventually wins approval for a related condition known as Peyronie’s disease, in which a bent penis makes intercourse painful or even impossible.

About one in 20 men is estimated to have Peyronie’s, but figures are not precise because people with the condition tend not to discuss it publicly...

... Some people treated with Xiaflex in clinical trials for the Dupuytren’s hand condition said it had made a big difference in their lives, and had allowed them to avoid painful surgery.

“When I looked down and saw my finger straightened out, I cried,” said Kenneth Nelson, 65, of Indianapolis. “It was to me just like a miracle.”

Xiaflex is an enzyme produced by a gangrene-causing bacterium, Clostridium histolyticum, which uses it to eat away the tissues of its victims. The enzyme, called collagenase, breaks down collagen, a major component of the body’s connective tissue that is found in skin, tendons, cartilage and other organs.

But collagenase by itself does not cause gangrene. And there are times doctors need to break down collagen, such as when an excess builds up in the hand or penis, causing Dupuytren’s and Peyronie’s. The ailments are named for French surgeons who described the conditions in the 18th and 19th centuries...

... Auxilium sought approval for treating Dupuytren’s first because it was easier to measure success in straightening fingers. But the company hopes to begin late-stage trials of Xiaflex for Peyronie’s disease later this year. In a midstage trial, injections of Xiaflex into the collagen plaque in the penis reduced the curvature. But the drug did not reduce pain or discomfort during intercourse by a statistically significant amount.

While collagenase itself is not patented, the companies do have patents on the use of the enzyme to treat Dupuytren’s and Peyronie’s. They are also shielded from competition for seven years under a federal law aimed at spurring development of drugs for rare, or “orphan,” diseases — even though newer estimates suggest these two diseases are not as rare as thought when the drugs were given orphan status...

This has been discussed for some time, so this is more of a milestone than major news. My suspicion is that if it does work at all, it will work best for persons early in the disease. Penile fibrosis appears to destroy tissues that will not regenerate, so even clearing the fibrosis does not mean restoring function.

Apologies for missing real comments

Most the comments I get on this blog are spam, typically for mail order viagra. I did miss several quite valid comments though, and I've just fished them out.

The blog obviously hasn't been very active. This is not because my fairly severe Peyronies has gotten any better. I don't think that's going to happen. It's mostly because my life is generally full of things that are either good or very demanding, and because there really isn't much new to say about this disorder.

I will try to catch up a bit more though.

Review of medical treament - nothing new

I've not added much to my blog posts because very little is happening with the understanding or management of Peyronie's Disease. I try to post when I find something novel.

This article doesn't have anything new, but it's a good summary of the urologist's current medical approach (emphasis mine and I've reformatted for readability):

Medical Management of Peyronie's Disease. [J Androl. 2008] - PubMed Result

Peyronie's disease (PD) is a wound healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction (ED).

Recent studies indicate that PD has prevalence of 3-9% in adult men.

While the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress.

For this reason authorities recommend a more conservative treatment approach with a trial of oral and/or intralesional pharmacotherapy before surgical reconstruction is considered.

Oral therapies most commonly employed include tocopherol (vitamin E), and para-aminobenzoate (Potaba), with colchicine, tamoxifen, propoleum and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo- controlled studies with these oral agents and for the most part, studies have failed to show a consistent beneficial effect.

Intralesional injection therapy for PD is more commonly being used as a first line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase.

Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density.

However, intralesional interferon is associated with post treatment flu-like symptoms unless premedicated with a non-steroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy (ESWT).

Surgery is considered when PD men do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse...

Translating from the jargon I'd summarize this as:

1. Most treatments have been shown not to work and should be abandoned.
2. Interferon-alpha-2b injection may be worth trying in the acute phase, but be ready for side-effects. I'd recommend asking for an explanation of exactly how much improvement was found, and whether the improvement was age group specific. Interferon injections have been proposed for many problems and they are usually found to be ineffective. This would be more persuasive if there were solid physiologic reasons to think it should work.
3. The "wound healing" explanation is not confirmed. I suspect the cause varies with age of onset, and that there may be a common predisposition both to injury and to dysfunctional healing.
   

The article does not address how well surgery works, it's a medical review. Long term surgical outcomes have been mixed at best.

The take away is to consider the interferon but cautiously. We haven't learned all that much about Peyronie's in the past 10 years, but at maybe we're using fewer ineffective treatments.

Dupuytren disorders site and Peyronie's disease (IPP)

A comment by Wolfgang on a prior post pointed to a web site on Dupuytren's disorder, which included this page - Diseases related to Dupuytren: Peyronie's disease (IPP). It's a great resource for persons with Peyronie's and I need to explore it further. On initial inspection it feels pretty evidence-based and very topical.

It's authored by a German scholar, written in English.

Dupuytren e.V.
Westerbuchberg 60b
83236 Übersee

Germany

Responsible for the content of this site:
Secretary/1. Vorsitzender: Dr. Wolfgang Wach

Dr. Wach is a Dupuytren patient, not a medical doctor.

Vitamin E: not harmless

Vitamin E is commonly prescribed for Peyronies Disease, even though it has been shown to have NO benefit and even though several studies have suggested that high dose Vitamin E is mildly toxic.

Today another study suggested Vitamin E may slghtly increase lung cancer diagnoses:

Vitamin E Supplements May Raise Lung Cancer Risk - washingtonpost.com...

Our study of supplemental multivitamins, vitamin C, vitamin E and folate did not show any evidence for a decreased risk of lung cancer,' study author Dr. Christopher G. Slatore, a fellow in the division of pulmonary and critical care medicine at the University of Washington, said in a statement...

... Every increase in vitamin E of 100 milligrams per day was associated with a 7 percent rise in lung cancer risk -- translating into a 28 percent increase in risk over 10 years for someone taking 400 milligrams of vitamin E daily....

A 28% increase in lung cancer risk still isn't in the range of second-hand smoke, but it's significant.

Vitamin E is worthless as a Peyronies treatment. It's probably not harmless in large doses.

Urologists should not prescribe it.

Device corporation launches "social networking" site for Peyronie's Disease -- and their "biodesign repair graft".

Cook Medical is a part of the Cook Group, an oddly diverse multinational (emphases mine):

Since 1963, Cook Group companies have been among the leaders in developing healthcare devices that have improved lives around the world. COOK remains at the forefront of medical research and worldwide sales of products for endovascular therapy, critical care medicine, general surgery, diagnostic and interventional procedures, bioengineered tissue replacement and regeneration, gastroenterology and endoscopy procedures, urology, and obstetrics and gynecology.

Our COOK corporate family also includes companies that manufacture specialized industrial parts and offer commercial services in the travel, real-estate development and management, and retail fields.

COOK is a global company with a global focus - and a global future.

Real estate services and endovascular devices? Now that's weird. I suspect they're privately held, which probably explains their idiosyncratic portfolio.

The medical device company, among other things, sells the Surgisis Biodesign Peyronie's Repair Graft

... The Surgisis Biodesign Peyronie's Repair Graft can help restore a patient's lifestyle and confidence. Surgisis Biodesign provides strength and flexibility for reinforcement and correction of penile curvature. The graft signals the body's surrounding cells to grow across the scaffold, remodeling into functional tissue. Surgisis Biodesign is easy to hydrate and suture, minimizes scar tissue formation, and is resistant to infection....

The Surgisis line appeared on "The History Channel" a few months ago, which leads to some cynical speculation on how that channel is funded. I couldn't find any medical articles referencing this product, a scholar.google.com search had one hit.

Which brings me to Peyronie's - Getting Information and Help. This is billed by Cook Medical as a "social networking site" (from an email I was sent):

... Cook Medical is launching MensHealthPD.com, and leveraging social networking capabilities to create a safe and interactive destination for physicians, patients and their partners to learn about symptoms and treatments, discuss and share thoughts and opinions and have access to the latest information around Peyronie’s disease.  Physicians can also engage in a secure, physicians-only Q&A forum to foster knowledge exchange...

Unsurprisingly their therapy reference includes this blurb:

... Plaque Incision or Excision and Grafting: This procedure removes tissue on the inside of the curve and replaces it with a graft to allow the penis to straighten. The graft can either be tissue from the patient or a biological "off-the-shelf" material such as Cook Medical's Surgisis^® Biodesign™ Peyronie's Repair Graft or a cadaveric pericardial graft...

Well.

Ok, so it's a time honored practice in the pharma industry to create "patient friendly" web sites which, oddly enough, slip in some marketing on the side. Even so, this one feels a bit a bit edgy to me. There are NO references to any published research about their "Surgisis Biodesign" graft material, and it's obviously the entire reason the site exists.

If you do visit this site, please remember why it exists.

Urologists - how they treat Peyronies Disease

Urologists are no more evidence based in their practice than most physicians ...

Urologist Practice Patterns in the Management of P...[J Sex Med. 2007] - PubMed Result

Introduction. Peyronie's disease (PD) is a poorly understood clinical entity. Aim. We endeavored to determine how contemporary urologists in the United States manage PD.

Methods. A randomly generated mailing list of 996 practicing urologists was generated from the American Urologic Association member directory. A specifically designed survey was mailed with a cover letter and a postage-paid return envelope. ...

...Results. Responses were received from 236 (24%) practicing urologists. Vitamin E was the preferred initial management for 70% of respondents, with observation, Potaba (Glenwood, Englewood, New Jersey, USA), colchicine, verapamil injections, and verapamil gel favored by 32, 20, 12, 7, and 10% of respondents, respectively. Fifty-seven percent of respondents performed surgery for PD, with penile prostheses, Nesbit procedure, grafting, and plication used by 76, 66, 55, and 51% of respondents, respectively. Medical therapy and/or observation was the preferred management for all of the cases except case 3, for which penile prosthesis placement and referral were the favored options by 39 and 30% of urologists, respectively...

Vitamin E does nothing and may have some toxicity in high doses. So it's unfortunate that 70% of urologists still use it. On the other hand, I suspect that the number would have been 90% a few years ago, so this probably is progress.

There's a bit more evidence for some other interventions, but none that I'm aware of for Potaba and precious little for cochicine.