Phase 2b safety data for Sildenafil Cream against FSAD reported

Phase 2b safety data for Sildenafil Cream against FSAD reported | Image Credit: © David L/peopleimages.com - © David L/peopleimages.com - stock.adobe.com.

Safety and tolerability data for Sildenafil Cream, 3.6% as on-demand treatment of female sexual arousal disorder (FSAD) from the phase 2b RESPOND clinical study has been published in The Journal of Sexual Medicine, according to Daré Bioscience, Inc.¹

FSAD presents as a persistent or recurrent failure to reach consistent and adequate sexual arousal during sexual activity. Patients with FSAD often experience distress or interpersonal difficulty, and FSAD has been estimated in 16% of US women aged 21 to 60 years, highlighting the need for safe and effective treatment.

Sildenafil is a phosphodiesterase-5 inhibitor used for the oral treatment of erectile dysfunction in men. Sildenafil Cream was designed as treatment of FSAD through topical administration to the vulvar-vaginal tissue, increasing genital blood flow while avoiding system side effects linked to orally administered sildenafil.

In the RESPOND study, the systemic and local genital safety of Sildenafil Cream was evaluated across 12 weeks in healthy premenopausal women with FSAD and their sexual partners. Sildenafil Cream was evaluated in 1357 sexual encounters and compared to placebo in 1160 sexual encounters.

Participants included women aged 18 years or older and their sexual partners.² Exclusion criteria included uncontrolled hypertension, serious cardiac event history, orthostatic hypotension, and other severe medical comorbidities. The trial included a 28-day no drug run-in period, followed by a single-blind placebo run-in period of the same length.

Randomization was 1:1 for Sildenafil Cream vs placebo cream, and assessments were performed monthly during the double-blind dosing period. Participants reported treatment emergent adverse events (TEAEs) and sexual events in an eDiary, which was reviewed at each monthly follow-up visit.

There were no significant differences reported in the prevalence of TEAEs among participants receiving Sildenafil Cream vs placebo, with mean times of onset of the first TEAE of 21 ± 11 days and 20 ± 8 days, respectively. Three TEAEs were reported by 2 participants receiving Sildenafil Cream.

TEAEs reported by these 2 participants included burning at application site, erythema at application site, and dyspareunia. These TEAEs were linked to the investigational product (IP) and led to discontinuation.

Placebo users reported 2 TEAEs, including dyspareunia and vulvar fissure. These TEAEs were not linked to the IP, but still led to discontinuation. Additionally, 9 TAEs were reported by 7 sexual partners exposed to Sildenafil Cream, vs 4 TEAEs among 4 partners exposed to placebo cream.

No significant differences in the number of participants using Sildenafil Cream experiencing at least 1 TEAE were observed when divided based on the number of reported sexual events. Additionally, the system organ class of TEAEs did not significantly differ between Sildenafil Cream vs placebo users and their sexual partners.

These results indicated topical sildenafil is safe and well-tolerated for healthy premenopausal women with FSAD and their sexual partners. Sildenafil Cream will continue to be evaluated in a phase 3 clinical trial in collaboration with the FDA.¹

“Because oral sildenafil has known hypotensive effects, we were watching for related side effects such as headache, flushing, nausea, and dizziness,” said Annie Thurman, MD, FACOG, lead author and Medical Director at Daré Bioscience. “In the RESPOND study with our topical application, however, we did not see these effects, likely due to the hundred-fold lower systemic exposure as compared to oral dosing of sildenafil.”

References

1. Daré Bioscience announces publication in The Journal of Sexual Medicine of positive safety findings from the phase 2b RESPOND clinical study of Sildenafil Cream, 3.6%. Daré Bioscience. August 26, 2024. Accessed August 26, 2024. https://www.globenewswire.com/news-release/2024/08/26/2935448/30757/en/Dar%C3%A9-Bioscience-Announces-Publication-in-The-Journal-of-Sexual-Medicine-of-Positive-Safety-Findings-from-the-Phase-2b-RESPOND-Clinical-Study-of-Sildenafil-Cream-3-6.html
2. Thurman AR, Johnson I, Cornell KA, et al. Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder. The Journal of Sexual Medicine. 2024. doi:10.1093/jsxmed/qdae089