Topical sildenafil cream found safe, tolerable in female sexual arousal disorder

Topical sildenafil cream (3.6%) was found to be safe and well-tolerated among premenopausal women with female sexual arousal disorder (FSAD) and their sexual partners, according to safety data from the phase 2b RESPOND trial (NCT04948151) published in the Journal of Sexual Medicine.¹

Preliminary efficacy data from the RESPOND trial were also published separately in the journal Obstetrics & Gynecology.

“Topical sildenafil cream was well tolerated in this study,” said lead author Annie Thurman, MD, FACOG, medical director at Daré Bioscience, in a news release on the findings.² “Because oral sildenafil has known hypotensive effects, we were watching for related side effects such as headache, flushing, nausea, and dizziness. 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.”

Overall, 78 treatment-emergent adverse events (TEAEs) were reported among 29 of 99 patients who received sildenafil cream vs 65 TEAEs reported among 28 of 94 patients who received placebo (P = .76). All TEAEs were mild or moderate in severity.

Additionally, there were no differences in the number of treatment-related TEAEs in patients who received sildenafil cream vs patients who received placebo (P > .99). The most common treatment-related TEAE was application site discomfort. In total, 4 patients in the sildenafil cream arm and 2 patients in the placebo arm discontinued the study due to application site discomfort (P > .99).

Regarding patients’ sexual partners, 9 TEAEs were reported by 7 of 91 sexual partners exposed to sildenafil cream compared with 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo (P = .54).

Efficacy of sildenafil cream

Preliminary efficacy data from the RESPOND trial were also published separately in the journal Obstetrics & Gynecology.³

The intent-to-treat population included only patients with FSAD and those with FSAD with concomitant sexual dysfunction diagnoses or genital pain. The dual primary efficacy end points for the trial were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale-Desire, Arousal, Orgasm).

Overall, no statistically significant differences were noted between the 2 cohorts in either of the 2 co-primary end points. However, patients in the sildenafil cohort did demonstrate a greater improvement in the SFQ28 Arousal Sensation domain score vs patients in the placebo cohort.

The investigators also conducted an exploratory post hoc analysis in patients with FSAD with or without concomitant decreased desire. In this subset of patients, those who received sildenafil cream demonstrated a significant increase in their SFQ28 Arousal Sensation domain score vs those who received placebo, with a least squares mean of 2.03 in the sildenafil cohort compared with 0.08 in the placebo cohort. Additionally, patients in the sildenafil arm achieved a larger average improvement in the SFQ28 Desire and Orgasm domain scores.

Patients who received sildenafil also experienced significantly reduced sexual distress and interpersonal difficulties vs patients in the placebo arm, as measured by questions 3, 5, and 10 of the FSDS-DAO questionnaire (all P≤.04).

Additional Information on the RESPOND trial

Overall, the phase 2b, exploratory, double-blind RESPOND trial assessed the safety and efficacy of sildenafil cream (3.6%) vs placebo in premenopausal patients with FSAD.

Patients included in the intent-to-treat population were randomly assigned 1:1 to receive either sildenafil cream (n = 99) or to placebo (n = 94). An additional 41 patients were included in the safety analysis from the 1-month placebo exposed run-in period. Women in the study used their product over a 12-week dosing period. Informed consent was obtained from both patients and their sexual partners.

In total, there were 1357 and 1160 sexual events recorded among participants in the sildenafil cream and placebo cohorts, respectively. Sexual partners were contacted within 72 hours of each sexual event in which a study treatment was used.

In the publication of the safety data, the authors concluded, “These data support further clinical development of topical sildenafil cream for the treatment of FSAD.”¹

References

1. 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. J Sex Med. 2024:qdae089. doi:10.1093/jsxmed/qdae089

2. 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%. News release. Daré Bioscience, Inc. August 26, 2024. Accessed August 27, 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

3. Johnson I, Thurman AR, Cornell KA, et al. Preliminary efficacy of topical sildenafil cream for the treatment of female sexual arousal disorder: A randomized controlled trial. Obstet Gynecol. 2024;144(2):144-152. doi:10.1097/AOG.0000000000005648