Analysis of the clinical safety of intralesional injection of collagenaseClostridium histolyticum(CCH) for adults with Peyronie's disease (PD)

Abstract

ObjectiveTo examine the safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie's disease (PD), using a pooled safety analysis of patients who received at least one dose of CCH in any of six clinical studies. Patients and MethodsPatients from six clinical studies, including three randomised, double-blind, placebo-controlled studies and three open-label safety and efficacy studies, were included if they had received at least one dose of 0.58 mg CCH. Adverse events (AEs), including treatment-emergent AEs, treatment-related AEs, and serious AEs (SAEs), were characterised. Potential immunogenicity-related AEs were evaluated through examination of increased anti-AUX-I and anti-AUX-II antibody levels, AEs, and reported terms possibly associated with immunological or hypersensitivity events. ResultsOverall, 85.8% of 1 044 pooled patients reported at least one treatment-related AE. The most frequently reported (≥25.0% of patients) treatment-related AEs included penile haematoma (82.7% had the verbatim 'penile bruising'), penile pain, and penile swelling. Most patients (75.2%) had mild-or moderate-severity treatment-related AEs, and 14.2% had no treatment-related AEs. Nine patients (0.9%) had treatment-related SAEs: five with penile haematoma and four with corporal rupture. There was no association between AEs and anti-AUX-I or anti-AUX-II antibody levels across treatment cycles, and no systemic hypersensitivity reactions occurred. ConclusionsThis pooled safety analysis shows that although non-serious and serious treatment-related AEs can occur after CCH treatment for PD, most were non-serious and the SAEs were manageable. Providers should be prepared to manage possible SAEs. Keywordspenile induration, Peyronie's disease, microbial collagenase, safety IntroductionPeyronie's disease (PD) is characterised by the formation of a fibrous collagen scar or plaque of the tunica albuginea, resulting in penile curvature deformity during erection (manifested as bending, narrowing, hinging, or shortening) and has been associated with significant concern about erection pain or appearance, with potential impact on sexual intercourse, and emotional and relationship distress [1,2]. Based on safety and efficacy demonstrated in the identical phase III, placebo-controlled Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies (IMPRESS) I and II trials, intralesional injection therapy with collagenase Clostridium histolyticum (CCH) was approved by the USA Food and Drug Administration (FDA) for the treatment of adult men with PD with a palpable plaque and curvature deformity of at least 30°at the start of therapy. CCH studies, including a phase IIb study and IMPRESS I and II, showed significant improvement in both penile curvature deformity and PD-specific psychosexual aspects (i.e., Peyronie's Disease Questionnaire PD Symptom Bother domain score), compared with placebo [3,4].CCH is a purified mixture of two microbial collagenases, AUX-I and AUX-II; studies suggest tha...

Collagenase Clostridium Histolyticum: A Review in Peyronie’s Disease

“…In addition, nine (0.9 %) CCH recipients had combined AEs of penile ecchymosis or haematoma, sudden penile detumescence and/or a penile 'popping' sound or sensation in which corporal rupture could not be excluded; all these patients were managed non-surgically. No treatment-related deaths were reported in CCH recipients [30].…”

“…Although antibodies against AUX-I and AUX-II were detected in C95 % of CCH recipients after two treatment cycles (B4 injections), data from phase III studies found no association between antibody titres and the incidence, duration or severity of the three most common AEs (penile haematoma, penile pain and penile swelling) or the four AEs possibly consistent with an immunologic event (pruritus, genital pruritus, injection-site pruritus, lymphadenopathy) [30]. There were no treatment-related severe Type 1 or Type 3 systemic hypersensitivity reactions with CCH therapy; three local rashes and three reports of mild local pruritus were considered drug-related and one patient discontinued treatment because of papular dermatitis considered probably drug-related [30].…”

“…A pooled safety analysis of data from six clinical studies (three phase IIb and three phase III; n = 1044), including the IMPRESS I and II studies, also showed that CCH intralesional injections were generally well tolerated in patients with PD [30]. Treatment-related AEs occurred in 85.8 % of CCH recipients in this analysis, most (75.2 %) of which were of mild or moderate severity; 14.2 % of patients did not experience any such AEs.…”

“…The most common (incidence [25 %) treatment-related AEs with CCH were penile haematoma (50.2 %), penile pain (33.5 %) and penile swelling (28.9 %). Severe treatment-related adverse events occurred in 10.6 % of CCH recipients, with severe penile haematoma reported in 39 (3.7 %) patients [30].…”

“…Nine (0.9 %) CCH recipients had serious treatment-related AEs (penile haematoma in five and corporal rupture in four patients), of which only four patients (0.4 %) required surgical intervention [30]. Two patients discontinued CCH treatment because of serious treatment-related AEs (one patient each with penile haematoma and corporal rupture) and seven patients because of non-serious treatment-related AEs.…”