AB009. Xiaflex as a treatment for Peyronie’s disease

Peyronie disease can be physically and psychologically devastating for subjects and their partners. Collagenase Clostridium histolyticum (CCh), a purified mixture of AUX-I and II collagenases, is an intralesional, minimally invasive intervention with evidence of tolerability and efficacy in subjects with PD and is approved by the United States Food and Drug Administration for use in adults who have Peyronie Disease and Dupuytren contracture. The Investigation for Maximal Peyronie’s Reduction Efficacy and Safety Studies (IMPRESS) I and II examined the clinical efficacy and safety of CCh intralesional injections in subjects with Peyronie disease. Primary outcomes in these identical phase 3 randomized, double blind, placebo controlled studies included the percent change in penile curvature and the change in the Peyronie disease questionnaire (PDQ) symptom bother score from baseline to 52 weeks. IMPRESS I and II examined CCh intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg CCh, comprising 2 injections per 6 week cycle separated by approximately 24 to 72 hours with subsequent penile plaque modeling within 24 to 72 hours. Men were stratified by baseline penile curvature (30 to 60 vs. 61 to 90 degrees) and randomized to CCh or placebo 2:1 in favour of the former. Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with CCh showed a mean 34% improvement in penile curvature, representing a mean ±SD −17.0±14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean −9.3±13.6 degree change per subject (P<0.0001). The mean change in PDQ symptom bother score was significantly improved in treated men vs men on placebo (−2.8±3.8 vs. −1.8±3.5, P=0.0037). Three serious adverse events (corporeal rupture) were surgically repaired. IMPRESS I and II support the clinical efficacy and safety of CCh for the physical and psychological aspects of Peyronie disease.