Studies suggest intracavernosal botulinum toxin A (BTX/A) could improve difficult-to-treat erectile dysfunction (ED) ie with an insufficient response to phosphodiesterase type 5 inhibitors (PDE5-Is).
To investigate efficacy and safety of intracavernosal injection (ICI) of BTX/A combined with sildenafil 100 mg on demand in patients with ED and insufficient response to PDE5-Is.
Double-blind, placebo-controlled, multicenter, randomized phase 2 trial to investigate the efficacy and safety of bilateral 0.5 ml ICIs of incobotulinumtoxinA 50 U or placebo, both combined with sildenafil 100 mg on demand in men with ED and insufficient response to sildenafil 100 mg on demand. The inclusion criteria were International Index of Erectile Function-Erectile Function (IIEF-EF) domain score < 17 and >50% of attempts at sexual intercourse unsuccessful during a 4-week open-label run-in phase with sildenafil 100 mg on demand.
Mean change in IIEF-EF score and the proportion of "Yes" responses to Sexual Encounter Profile (SEP)-Q2 (ability to penetrate) and SEP-Q3 (ability to maintain an erection for successful intercourse) at 3 months.
Out of 226 patients screened, 165 patients were randomized (mean age: 60.1 years, mean IIEF-EF on sildenafil 100 mg: 11.1). Intention-to-treat (ITT) analysis showed no significant improvement in IIEF-EF score with incobotulinumtoxinA 100 U combined with sildenafil 100 mg at 3 months. IncobotulinumtoxinA 100 U improved penetration (SEP-Q2) and erection maintenance (SEP-Q3), but not significantly. These results were confirmed by the complete-case and per-protocol analyses. Adjusted analysis for 100% adherence to sildenafil 100 mg showed a significant interaction effect (P = .032), suggesting greater IIEF-EF improvement in fully compliant patients. The safety profile was positive.
IncobotulinumtoxinA 100 U combined with sildenafil 100 mg on demand is safe; however, there is yet no robust evidence to support its use to treat ED.
Main strengths include the double-blind, placebo-controlled design, which was preceded by an open-label run-in phase, a 3-month follow-up, the use of ITT analysis and meaningful outcome measures. Limitations include no adherence to sildenafil (28%), inconsistent clamping at the penile crus post-incobotulinumtoxinA injection, and an underpowered sample size due to an overestimated treatment effect.
Despite negative ITT effectiveness results, this study demonstrated the safety of intracavernosal BTX/A. The results raise hypotheses regarding its potential role in combination with PDE5-Is, warranting further investigation. Future trials should refine patient selection and injection technique, assess dose-response effects, and improve protocol adherence to yield more reliable results for ED resistant to PDE5-Is.
The journal of sexual medicine. 2025 Sep 16 [Epub ahead of print]
Francois Giuliano, Anne-Charlotte Denormandie, Francois-Xavier Madec, Damien Carnicelli, Jean-Pierre Graziana, Stéphane Droupy, Francois Marcelli, Malamine Gassama, Lamiae Grimaldi, MENOX study group
Neuro-Uro-Andrology Department, R. Poincaré Academic Hospital 92380 Garches, Versailles-Saint Quentin-en-Yvelines University/Paris-Saclay, France., Urology Department, Academic Hospital Pitié-Salpétrière, AP-HP, 75014 Paris, Sorbonne Université, France., Urology Department, Foch Hospital,92073 Suresnes, Versailles-Saint-Quentin-en-Yvelines University, Paris-Saclay, France., Department of Urology, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon Est and Lyon Sud Medical School, Claude Bernard University Lyon 1, 69152 Pierre-Bénite, France., Urology Clinique Mutualiste de la Porte de l'Orient, 56100 Lorient, France., Urology and Andrology Department, Nimes University Hospital, 30000 Nimes, France., Department of Andrology, Urology and Renal Transplantation, CHU Lille, University of Lille, 59000 Lille, France., Clinical Research Unit, Ambroise Paré Hospital, University of Versailles Saint-Quentin-en-Yvelines, 92012 Boulogne-Billancourt, France.