Peyronie’s disease affects the penis and it is characterized by the presence of a collagen plaque on the shaft of the penis, which can distort an erection and make intercourse difficult or impossible in advanced cases. The plaque is not elastic and it does not stretch during erection. In some mild cases, the plaque can resolve spontaneously without medical intervention. The most common plaque forms on the top of the penis causing the penis to arc upward. In severe cases, the penis can be bent at a 90-degree angle during erection. Significant psychological distress has been noted in patients with Peyronie’s disease who are sexually active. Frequent patient complaints include increased pain, painful erections, palpable plaque, penile deformity, and erectile dysfunction. Patients with Peyronie’s disease have been reported to have an increased likelihood of having Dupuytren’s disease, frozen shoulder, plantar fibromatosis, knuckle pads, hypertension and diabetes. Peyronie’s disease typically affects males in the range of 40-70 years. The cause of Peyronie’s disease is unknown, although some investigators have proposed that it may be due to trauma or an autoimmune component. A number of researchers have suggested that the incidence of Peyronie’s disease has increased due to the use of erectile dysfunction drugs.

Surgery is the only proven treatment for Peyronie’s disease and the results are variable. Surgery often results in shortening of the penis. Auxilium has reported that 33% of Peyronie’s disease patients who undergo surgery are subsequently dissatisfied with the results and they frequently require a penile implant.

Patients with Peyronie’s disease strongly desire therapeutic alternatives to surgery. Auxilium has reported that 90% of urologists would use collagenase injection to delay or avoid surgery and this finding is consistent with a survey of urologists performed for us.

Collagenase Treatment for Peyronie’s Disease

Histological and biochemical studies indicate that the scarring on the penis due to Peyronie’s disease is composed primarily of collagen.

An independent investigator carried out a Phase 1 clinical investigation in which he treated approximately 180 patients in an open label trial.

Since 1999, two positive open label clinical trials have been conducted by an independent investigator at Tidewater Urology in Norfolk, Virginia, which is the largest center for treatment of Peyronie’s disease in the world.

Auxilium announced on October 25, 2006 the results of two Phase 2 trials. They stated:

Both studies were open label and up to 12 months in duration. They were conducted to evaluate the efficacy and tolerability of AA4500 in the treatment of Peyronie’s disease. Clinical success was defined as change from baseline in deviation angle of at least 25 percent.

In Study A (n=25) [25 patients], 3 injections of AA4500, each administered on a separate day, were given over 7-10 days. Patients received a second series of 3 injections 12 weeks later. Patients were evaluated at three, six, and nine months post-last injection. The mean baseline deviation angle was 52.8 degrees. At months three and six, 58 percent and 53 percent of patients (respectively) achieved clinical success with respect to deviation angle.

The best results were achieved with a three-treatment series of three injections each in Study B (n=10) [10 patients]. In Study B, patients received three injections of AA4500 administered one per day, separated by at least one day each, over a one week timeframe. Patients received two additional series of 3 injections, each spaced 6 weeks apart. The mean baseline deviation angle was 50.2 degrees. At 9 month follow up (post-first injections), 25 percent or greater reduction in deviation angle was achieved in 8/9 patients who completed the study (89 percent, 1 patient had 24 percent reduction in deviation angle). Based on the investigator’s global assessment, 67 percent of subjects were very much improved or much improved after treatment with AA4500.

The most common adverse events reported in both studies were local administration site reactions that were mid or moderate in severity, non-serious, and resolved in time without medical attention.

Development Status

As of the date of this filing, Auxilium is reporting that they will initiate in 2007 a Phase 2b trial for Peyronie’s disease.

Peyronie's Disease References:

Useful Websites:

http://kidney.niddk.nih.gov/kudiseases/pubs/peyronie/

http://www.niddk.nih.gov/kudiseases/pubs/peyronie

http://www.centerwatch.com/studies/CAT118.HTM

http://www.peyronies.org/

Literatures:

1. Gelbard, M.K., Lindner, A., Kaufman, J.J. The Use of Collagenase in the Treatment of Peyronie's Disease. J. of Urology: 134, August 1985, 280-283

2. Gelbard, M.K., Walsh, R., Kaufman, J.J. Collagenase for Peyronie's Disease Experimental Studies. Urol. Res. (1982) 10:135-140

3. Hamilton, R.G., Mintz, G.R., Gelbard, M.K. Humoral Immune Responses in Peyronie's Disease Patients Receiving Clostridial Collagenase Therapy. J. of Urology 135: 641-647, March 1986

4. Gelbard, M.K., James, K., Riach, P., Dorey, F. Collagenase Versus Placebo in the Treatment of Peyronie's Disease: A Double-Blind Study. J. of Urology Vol. 149: 56-58 January 1993