Simenafil improves erectile function in Phase 2 trial for men with ED

BACKGROUND: Simenafil, a new potent selective phosphodiesterase-5 inhibitor (PDE5i), has been developed for erectile dysfunction (ED) treatment. AIMS: To evaluate the efficacy and safety of simenafil therapy in patients with ED. METHODS: A randomized, double-blind, placebo-controlled, multicenter, parallel-group, phase 2 trial was conducted in men aged ≥22 years with a history of ED of 3 months or more. The subjects were randomized in a ratio of 1:1:1:1 to on-demand receive either placebo or simenafil at fixed doses of 5, 10, and 20 mg for 8 weeks. OUTCOMES: Primary efficacy endpoints were the least square mean (LSM) changes from baseline to week 8 in the erectile function (EF) domain of the International Index of Erectile Function (IIEF), percentages of "yes" responses to Sexual Encounter Profile (SEP) diary Question 2 (SEP Q2: Were you able to insert your penis into your partner's vagina?) and Question 3 (SEP Q3: Did your erection last long enough for you to have successful intercourse?). RESULTS: A total of 255 patients were randomized. After 8 weeks of treatment, doses of 5, 10, and 20 mg of simenafil exhibited substantial increases than placebo in IIEF-EF score (9.7, 9.2, 9.5 vs. 5.5, P < .001), the percentages of "yes" responses to SEP Q2 (36.11%, 30.79%, 33.12% vs. 19.56%, P < .01), and SEP Q3 (55.96%, 51.14%, 51.05% vs. 31.02%, P < .001). The incidence of adverse drug reactions was 36.5%, 44.3%, 45.9%, and 61.7% for the placebo, 5 mg, 10 mg, and 20 mg simenafil groups, respectively. Overall, the adverse events were generally mild or moderate. CLINICAL IMPLICATIONS: Simenafil could effectively improve erectile function and the adverse reaction profile of simenafil was consistent with its pharmacological mechanism, with most adverse reactions being mild to moderate. The results provide a rationale for further evaluation in larger and longer-term phase 3 clinical trials. STRENGTHS & LIMITATIONS: We did not conduct a head-to-head study comparing the efficacy and safety of simenafil with other PDE5 inhibitors. Meanwhile, we did not further analyze the efficacy and safety of simenafil in specific populations, such as ED patients with diabetes. CONCLUSION: Simenafil is an effective and well-tolerated treatment for men with ED.