Clinical Safety and Effectiveness of Collagenase Clostridium Histolyticum Injection in Patients with Peyronie’s Disease: A Phase 3 Open-Label Study

Abstract

Introduction Collagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration-approved, intralesional treatment for Peyronie’s disease (PD). Aim The aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD. Methods This phase 3, open-label study enrolled subjects who were CCH-naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24–72 hours apart, and plaque modeling 24–72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles. Main Outcome Measures The co-primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0–16) from baseline to week 36. Results Of the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronie’s Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment-related AEs, two penile hematomas and one corporal rupture; all resolved with treatment. Conclusions Potentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open-label study support the use of CCH in the treatment of PD.

Evaluation of the benefit of using a combination of autologous platelet rich-plasma and hyaluronic acid for the treatment of Peyronie’s disease

“…A comparison of our data with other intralesional injection trials, especially both Impress I and II series of the Xiapex ® trial [7], shows slightly better results, particularly if only the patients without calcifications as those enrolled in the Xiapex ® trial are considered (Figure 4). Moreover, contrary to Xiapex ® [18], where it seems that after three cycles of treatment there is no more improvement, addition of sessions of PRP combined with HA after the first cycle of four, improves the results.…”

“…Nevertheless, available previous placebo -controlled studies [7] show a maximum angle reduction of 21% with Impress I and of 15.2% for the placebo group. Furthermore, the comparison of our results with those of untreated patients, as in Berookhim's trial [17] conducted on 176 patients to study the natural history of PD in the absence of medical or surgical therapy, further supports a beneficial effect of the combination of PRP and HA, as only 12% of untreated patients had an improvement of their deformation vs 62% in the present study.…”

“…Deformation, consisting of curvatures (angulation in degrees) and/or shaft strictures was measured on photographs of fully erected penis [7].…”

“…More recently, Hyaluronic Acid (HA) (7) and Botulinum toxin [8] have also been proposed with the purpose of counteracting tunica fibrosis, the final issue of the pathological process of PD, before the deposit of calcifications [4]. We hypothesized that regenerative medicine could help stop the process and restore function.…”

“…An increasing knowledge of the pathophysiology [3] of the disease has urged clinical researchers to propose intralesional treatments [4] such as verapamil [5] and interferon alpha 2B [6] which remain off label, or collagenase clostridium histolycum (CCH) ( Xiapex ® ) which obtained an FDA approval [7] for Peyronie's disease (PD). The interesting improvement rates observed with these treatments are challenged by side effects such as corporeal ruptures for CCH, flu-like symptoms for interferon alpha 2B, or penile bruising, dizziness and nausea for verapamil.…”