Regulatory Decision Summary for Xiaflex

Peyronies Disease (PyD) is a disorder of the penis resulting in penile curvature most evident during an erection. This often leads to significant inconvenience and diminished quality of life, distress, and limitation of normal sexual function. There is no authorized medical treatment for PyD. The standard of care is surgical correction, which may result in a straighter penis, but could be complicated by penile shortening, erectile dysfunction, urethral perforation and infection, and nerve damage.

The Sponsor conducted two identical double-blind, placebo-controlled, multicenter Phase 3 studies of Xiaflex (collagenase clostridium histolyticum). A total of 832 healthy adult subjects with symptomatic but stable PyD for at least 12 months and penile curvature of 30 to 90 degrees were enrolled in the United States and Australia.

Two pivotal trials have shown that Xiaflex is efficacious in reducing penile curvature and improving patients perceptions of their PyD status. The co-primary endpoints for both studies (Study 5 and Study 6) were percentage (%) change from baseline in penile curvature, and change from baseline in the "PyD bother" domain score. The latter was a component of the Peyronies Disease Questionnaire (PDQ), completed only by sexually active subjects. The co-primary endpoints were met in both studies and additional sensitivity analyses demonstrated that the findings were robust despite missing data. The estimated % changes in penile curvature deformity were -17.5% (p-value <0.0001) and -14.3% (p-value <0.0001) for Study 5 and Study 6, respectively. The estimated changes in PDQ Bother Domain Score were -1.4 (p-value <0.0001) and -0.8 (p-value <0.0001) for Study 5 and Study 6, respectively.

In the pivotal studies, adverse events (AEs) occurring in ≥1.0% of Xiaflex subjects and at a greater incidence than placebo after 4 treatment cycles were (in order of decreasing frequency): penile ecchymosis, penile swelling, penile pain, blood blister, penile blister, pruritus genital, painful erection, erectile dysfunction, skin discolouration, procedural pain, injection site vesicles, localized edema, dyspareunia, injection site pruritus, nodule and suprapubic pain. The 7 AEs leading to study discontinuation were individual events of blood blister, penile swelling, erectile dysfunction, contusion, penis disorder, and 2 of penile hematoma. Three deaths among Xiaflex subjects were deemed unrelated to study drug. The 9 serious AEs (SAEs) attributed to Xiaflex were: 4 corporal ruptures and 5 penile hematomata.

The Sponsor will implement a peer-to-peer training program to ensure that correct technique is used in the performance of injections and related procedures. The benefit/risk profile of Xiaflex in PyD is positive.