Palmer, Bruce

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously published outcomes of men undergoing a novel protocol for CCH injections and which demonstrated significant improvements compared to original IMPRESS I and II techniques. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men were randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes were compared between treatment and control groups. Key measures included objective curve improvements and standardized/non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 22/40 men have been randomized to date, with 11 having fully completed treatment. Mean age was 64 years, with a median PD duration of 24 months. Mean composite baseline curvature was 80 degrees, with 55% having hourglass or indentation deformities, 10% calcification, median baseline IIEF-EFD 15, and 60% able to have penetrative intercourse. Median estimated improvement with the prior CCH series was 0% (IQR 0, 19.4), and the median number of prior injections was 8. The majority of men were dissatisfied with their prior series of CCH (60% vs 30% satisfied, 10% neutral). Of the 11 men who had completed the study protocol, 64% required 1 series, 9% 2 series, 18% 3 series, and 9% 4 series. Compared to the no treatment arm, treated men experienced significantly greater improvements (mean 78 degree vs 15, p=0.01). IIEF-EFD was also improved more in treated men (+4.3 vs -5.7, p<0.05). 100% of men reported a subjective major improvement in curvature, with the average subjectively estimated improvement 91%. 67% reported improved sensitivity (33% no change), while 60% reported improved or no change in erectile function, with 20% unsure, and 20% somewhat worse. Post-treatment, 83% of men were very satisfied with CCH as a treatment and 17% somewhat satisfied. Conclusions Repeating CCH using a novel protocol after an initially unsuccessful course of CCH achieves significant improvements in curvature and patient satisfaction. Additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Matthew Ziegelmann - Endo Pharmaceuticals.

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously reported outcomes of men undergoing a more aggressive protocol for CCH injections. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel, aggressive protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men are randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes are subsequently compared between treatment and control groups. Key measures include objective curve improvements, and standardized / non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 11/40 men have been randomized to date, with one having completed four series of CCH injections, three completing one series, and three completing two series. The average age of the cohort is 64.4 years, with a mean PD duration of 28.1 months. Mean baseline curvature was 82.9 degrees (composite curve). The average estimated improvement with prior CCH injections (before enrollment in the current study) was 10%. Preliminary outcomes of men who had completed one series and had a follow-up curve assessment available (n=3) demonstrated an absolute improvement of 28.3 degrees (42%). Of the one patient who completed four full series, the absolute curve improvement was 55 degrees (65%). The overall range of improvement among the four men was 20 to 55 degrees or 31 to 65%, with no patients failing to experience improvements thus far. Conclusions Preliminary data suggests that a repeat course of CCH using a previously described more aggressive administration protocol is effective at improving penile curvature in the majority of men. It is unclear if the improvements are due to the difference in administration protocol, or due to the repeat course of CCH alone. Given the very preliminary nature of the current results, additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study