Hurley, David

Abstract Introduction Significant clinical variations exist in the definitions of acute/active vs chronic/stable Peyronie’s Disease (PD). While the American Urological Association’s 2015 guidelines define the acute phase as involving symptoms that change and the presence of pain, they do not specify a timeframe. Historically, acute-phase features include penile pain and worsening curvature, with symptom duration ranging from less than 3 to 18 months. Although temporally categorizing PD may have academic value, it may unnecessarily limit or delay treatment. In the United States, collagenase clostridium histolyticum (CCH) is the only FDA-approved treatment for adult men with PD who have a palpable plaque and a curvature deformity of at least 30 degrees. Several real-world studies suggest CCH is safe and effective during the acute phase. Objective To evaluate differences in outcomes by penile pain and symptom duration and to determine whether these factors should inform timing of CCH treatment in men with Peyronie’s disease. Methods A post hoc analysis of pooled data from 2 phase 3 randomized double-blind trials of CCH in PD (IMPRESS I, NCT01221597; IMPRESS II, NCT01221623). Men treated with CCH were stratified by baseline penile pain (Any Pain vs No Pain), based on both investigator-assessed and patient-reported measures. A subgroup analysis further stratified men with Any Pain by disease duration. The primary efficacy endpoint in the phase 3 study was the percentage change in penile curvature from baseline to week 52. A 2-sample t test was used to compare group means for each pain-related measure. Results A total of 364 CCH-treated men were included. Mean penile curvature improvements at week 52 were similar across all 4 investigator-assessed and patient-reported penile pain measures (35.0%-36.7% improvement for the No Pain group vs 32.2%-33.9% improvement for the Any Pain group, P=0.14-0.65). Among those experiencing Any Pain, no statistical differences were observed in men with disease durations that were shorter (12-18 months; 21.8%-34.8% improvement) vs longer (greater than 18 months; 31.4%-36.8% improvement, P=0.20-0.95). Conclusions This study found similar curvature improvements among men treated with CCH regardless of baseline pain or disease duration. Results align with prior studies showing no outcome differences by pain status or disease phase. These findings suggest that pain and disease duration should not be viewed as contraindications to CCH or used to guide clinical decision-making. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc. Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction While most patients with Peyronie’s disease (PD) present with dorsal or lateral curvature, a significant number have ventral curvature (VC). These patients face limited treatment options, as they were excluded from initial clinical trials of collagenase clostridium histolyticum (CCH) due to safety concerns related to the proximity of the injection site to the urethra. However, urethral involvement is rare, as PD plaques develop in the tunica albuginea rather than the corpus spongiosum surrounding the urethra. Moreover, multiple prospective and retrospective studies have demonstrated favorable outcomes with CCH treatment in men with VC. Objective To evaluate the effectiveness and safety of CCH in men with PD and VC in a multicenter, real-world, retrospective study. Methods This is an ongoing phase 4, multicenter, retrospective review of medical records from 15 US physician sites. Eligible patients consisted of patients who are: age ≥18 years with a diagnosis of VC in PD with a palpable plaque that was treated with CCH from 2014 to the study start date at each site. Patients missing baseline (BL; pretreatment) or final (last measurement within 6 months of final CCH treatment) penile curvature measurements were excluded. Effectiveness endpoints included percentage change in VC from BL to last visit, mean change in VC (in degrees) from BL to last visit, and proportion of patients with ≥30% improvement in VC from BL to last visit. Safety was assessed as proportions of patients reporting treatment-related adverse events (TRAEs) throughout the study period. Results As of April 22, 2025, there were 116 patients with mean (SD) age of 58 (10.3) years who were eligible for analysis. Mean baseline VC decreased from 58 degrees to 37 degrees at last visit (37% improvement). An improvement in VC of ≥30% was seen in 73/116 (63%) of patients, with 81/116 (69.8%) experiencing ≥20% improvement. At least 1 TRAE was reported by 12 (10%) patients. TRAEs were mild-to-moderate in severity in 9 (75%) patients and unknown in 3 patients, with most events (14/17 [82%]) related to injection site reactions. As of the data cut, there were no treatment-related serious or treatment-related severe AEs, no reports of urethral involvement or injury, and no reports of corporal rupture. Conclusions Men with PD who present with ventral curvature represent an underserved patient population. Concerns about potential urethral injury pose a significant barrier to both minimally invasive and surgical treatments, thereby limiting available therapeutic options. These updated results from a multi-institutional real-world clinical cohort align with previous findings, and demonstrate that the clinical effectiveness and safety profile of CCH is consistent with the profile of CCH seen in other clinical presentations of PD. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA, Inc Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo USA, Inc.

Abstract Introduction Peyronie’s disease (PD) is a connective tissue disorder characterized by the replacement of normal elastic fibers of the tunica albuginea with collagen-containing plaques. This alteration may result in penile deformities that are most evident during erection, which can lead to significant emotional distress, sexual dysfunction, and penile pain. Collagenase clostridium histolyticum (CCH) is indicated for the treatment of adult men with PD with a palpable plaque and curvature deformity of at least 30 degrees at therapy onset. Notably, men with ventral curvature (VC) were not included in the CCH clinical trial program due to potential concerns over the proximity of the urethra to the site of injection. Currently, CCH is contraindicated in Peyronie’s plaques that involve the penile urethra. Urethral involvement of a PD plaque is rare due to the anatomy of those structures. PD plaques form in the tunica albuginea as opposed to the corpus spongiosum which directly surrounds the urethra. Also, multiple prospective and retrospective studies have documented favorable outcomes using CCH for PD with VC. Thus, CCH may be a reasonable treatment option for patients suffering with ventral and ventrolateral penile curvatures in the absence of direct urethral involvement. Objective We are conducting a multicenter real-world retrospective collaborative research study of the safety and effectiveness of CCH in the treatment of men who had PD with VC. Methods A Phase 4, multicenter, noninterventional, retrospective review of medical records from approximately 10-15 US physician sites is being conducted. Eligible patients include those ≥18 years old with a PD diagnosis with VC and a palpable plaque that had been treated with CCH from 2014 to the study start date at the site. The primary effectiveness endpoint is percent change from (pretreatment) baseline in degree of VC at the last visit as measured at follow-up within 6 months post-treatment. Secondary endpoints include mean change from Baseline in VC and the proportion of patients with ≥30% improvement from baseline in VC at the last visit during which a measurement was collected within 6 months of final CCH treatment. Adverse events are collected throughout the study period to assess safety. Results In this first look at early data, 32 eligible patients with a median age (range) of 58.0 years (25-75 years) were included in the analysis. The percent change in penile curvature from baseline decreased, representing an improvement of 45.4% (SD: 28.62 [0-100]) (Figure), with 68.8% (22/32) of patients experiencing ≥30% improvement from baseline in VC. There were no serious adverse events. Five patients had at least one treatment-related adverse event (TRAE); 4 TRAEs were mild-to-moderate in severity and 2 were unknown. There were no reports of urethral involvement or injury. TRAEs were related to injection site bruising (n = 3), hemorrhage (n = 1), swelling (n = 1), and muscle spasm (n = 1). Conclusions This first look at early data reflecting improvements in men with PD and VC (data cutoff: 06/14/2024) is consistent with findings of effectiveness and tolerability of CCH in the treatment of men with dorsal and dorsolateral penile curvature. Disclosure Yes, this is sponsored by industry/sponsor: Endo USA Inc. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: MZ is an investigator and consultant for Endo USA Inc. MI is an investigator for Endo USA Inc. AT is an investigator and consultant for Endo USA Inc. RB is an investigator for Endo USA Inc. JM is an investigator and consultant for Endo USA Inc. JT is an employee of Endo USA Inc. DH is an employee of Endo USA Inc. GK is an employee of Endo USA Inc. KG is an investigator and consultant for Endo USA Inc. JA is an employee of Endo USA Inc. TR is an employee of Endo USA Inc. MA is an employee of Endo USA Inc. JM is an investigator for Endo USA Inc.