Efficacy and safety of hyaluronic acid and enzymatic mix intralesional therapy in Peyronie's disease: a prospective, randomized, controlled pilot study of outcomes and patient satisfaction.

INTRODUCTION

Peyronie's disease (PD) is characterized by fibrotic plaque formation leading to penile curvature. Xiapex's 2020 withdrawal from Europe eliminated validated intralesional therapies. This study evaluated the efficacy and safety of an intralesional hyaluronic acid-enzymatic mix (Fibrorestil: 0.05% sodium hyaluronate + recombinant collagenase/lyase/lipase) added to daily tadalafil and penile traction versus conservative therapy alone in men with stable-phase PD.

METHODS

This prospective, randomized, open-label, multicenter pilot trial (June 2023-March 2025; ClinicalTrials.gov NCT07341529; HUPHM-85-21) enrolled 38 men with stable PD, palpable plaque, and 30°-90° curvature. Group A received three intralesional sessions with plaque tunneling plus Andropenis extender (≥4 hours/day) and tadalafil (2.5-5 mg/day). Group B received traction and tadalafil (conservative therapy) alone. Assessments were performed at baseline and week 28. Analyses used intention-to-treat (n = 38) and per-protocol (n = 34) approaches, with Mann-Whitney U tests. Primary outcomes were absolute and relative curvature change (responders ≥15° improvement). Secondary outcomes included Peyronie's Disease Questionnaire (PDQ) changes; IIEF-EF minimal clinically important difference; satisfaction; and Clavien-Dindo adverse events.

RESULTS

Baseline curvatures was higher in Group A (60° [50;70] vs 45° [30;60], P = .037) with Group B showing more diabetes, numerically more hourglass deformity and calcified plaques, and shorter disease duration. Per-protocol curvature change was -15.0° [-20.0; -10.0] (27.3%; 52.9% responders) in Group A versus 0.0° in Group B (P = .001); final curvature was comparable (50° vs 45°, P = .786). ANCOVA adjusting for baseline curvature showed an adjusted between-group difference of 14.1° (P = .001). An exploratory multivariable model additionally adjusting for diabetes, calcification, disease duration, and hourglass deformity attenuated this effect (-6.1°, 95% CI -17.7 to 5.5; P = .288); given the small sample relative to covariates, this estimate is statistically fragile and hypothesis-generating rather than confirmatory. PDQ symptom-bother improved significantly in Group A [-1.5; P = .003], with numerical gains in total [-6.0 vs -2.5; P = .149] and physical-psychological [-3.5 vs -1.0; P = .110] domains. Satisfaction ("satisfied/very satisfied") was reported by 70.6% of Group A versus 11.8% of Group B (P = .001). Extender adherence >4 hours/day predicted response (88.9% vs 12.5%; P = .003). Only mild (Clavien-Dindo I) adverse events occurred (36.8% in Group A versus 5.3%).

CONCLUSION

Fibrorestil intralesional therapy demonstrates possible improvements in curvature and patient-reported outcomes versus conservative care in stable-phase PD and appears safe, while conservative care alone showed no meaningful improvement. Given baseline imbalances, small pilot sample size, open-label design, and lack of an equivalent sham injection control, these findings should be considered exploratory and require confirmation in larger randomized trials.