Efficacy of sildenafil cream for FSAD maintained across patient subgroups

Data from a post-hoc analysis of the phase 2b RESPOND trial (NCT04948151) showed no significant impact of age, race, or hormonal contraceptive use on the efficacy of topical sildenafil cream, 3.6%, among premenopausal women with female sexual arousal disorder (FSAD).¹

Daré Bioscience plans to initiate a phase 3 trial of sildenafil cream, 3.6%, in patients with FSAD in 2025.

The data were published in the journal Sexual Medicine.

“This analysis explored subgroups such as hormonal contraceptive users vs non-users,” said Annie Thurman, MD, FACOG, medical director at Daré Bioscience, in a news release on the findings.² “Since hormonal contraceptive use has been associated with lower sexual desire as well as reduced sexual arousal in other studies, we wanted to understand how this medication use might impact the effect of sildenafil cream. Our data show, however, that there was no significant impact from hormonal contraceptive use on either the primary or secondary efficacy end points, so we were also pleased to see that hormonal contraceptive users could also potentially benefit from sildenafil cream.”

In total, the phase 2b RESPOND trial enrolled 200 patients with FSAD across 49 clinical trial sites in the US. The intent-to-treat population included 192 patients. Participants were randomly assigned 1:1 to received either topical sildenafil cream (n = 99) or to placebo cream (n = 93).

The primary end points for the trial were the change from baseline to week 12 in the Arousal Sensation (AS) domain of the Sexual Function Questionnaire (SFQ28) and question 14 (Q14) of the Female Sexual Distress Scale – Desire, Arousal, Orgasm (FSDS-DAO). The trial’s secondary efficacy end point was the change from baseline to week 12 in the average number of satisfactory sexual events (SSEs) reported.

Data from the post-hoc analysis of the trial showed that “Age group (≥18 years and ≤ 45 years vs >45 years), race group (White vs non-White), and baseline use/non-use of hormonal contraception did not significantly affect the co-primary end points of the SFQ28 AS domain and FSDS-DAO Q14 (P values > .11).”¹

Within the sildenafil cohort, those who were aged 18 to 45 years, non-White, and were hormonal contraceptive users demonstrated larger improvements in the SFQ28 AS domain compared with those who were older than 45 years, White, and did not use hormonal contraceptives. However, the authors note that "formal statistical comparisons of within treatment groups were not part of the pre-planned subset analyses."

Both in the sildenafil cream arm and the placebo arm, those who were daily psychiatric medication users reported decreases in SFQ28 Desire domain scores from baseline to week 12. Among non-users of daily psychiatric medications, those in the sildenafil arm reported an increase of 1.85 ± 0.55 in the SFQ28 Desire domain score, and those in the placebo arm reported an increase of 0.52 ± 0.58, though this difference did not reach statistical significance (P = .10).

According to the authors, “Our findings of lower SFQ28 Desire domain scores among daily psychiatric medication users, whether assigned to sildenafil cream or placebo cream, are consistent with this well-known side effect of these medications.”¹

On the trial’s secondary end point, age and baseline hormonal contraceptive use had no significant impact on the change in the average number of SSEs from baseline to week 12 (all P values > .67).

Non-White participants receiving sildenafil cream reported an increase of 0.7 ± 0.63 SSEs at week 12. Conversely, non-White participants receiving placebo cream reported a decrease of 1.5 ± 0.58 SSEs at week 12 (P = .02).

Next Steps

Following the publication of these data, Daré Bioscience announced plans to initiate a phase 3 trial of sildenafil cream, 3.6%, in patients with FSAD.³ The company plans to submit their protocol and analysis plan to the FDA in Q1 of 2025, with plans to commence the phase 3 trial in mid-2025.

“We have appreciated the FDA’s collaboration on the phase 3 design for this novel therapeutic indication for women,” said Sabrina Martucci Johnson, president and CEO of Daré Bioscience, in the news release.³ “While increased attention has been focused on female sexual dysfunctions over the past several years, no pharmacologic options have yet been FDA approved for FSAD, a condition which significantly compromises a woman's ability to have a pleasurable sexual experience. We are excited about the potential for Daré’s sildenafil cream formulation to address this critical unmet need in women's sexual health, and that there is a clear path forward on how to evaluate the safety and efficacy of this novel formulation of the same active in Viagra so that women may have access to a safe, effective, and ‘on demand’ solution to difficulties with sexual arousal, allowing for a more intense and enjoyable sexual experience.”

According to Daré, a second confirmatory phase 3 trial will still be required to support a New Drug Application submission to the FDA for sildenafil cream, 3.6%.

References

1. Johnson I, Thurman AR, Cornell KA, et al. Impact of age, race, and medication use on efficacy endpoints in a randomized controlled trial of topical sildenafil cream for the treatment of female sexual arousal disorder. Sex Med. 2024;12(5):qfae079.doi:10.1093/sexmed/qfae079

2. Daré Bioscience announces publication in Sexual Medicine of positive findings from demographic, behavioral and medication use subgroup analyses in the phase 2b RESPOND clinical study of sildenafil cream, 3.6%. News release. Daré Bioscience, Inc. December 10, 2024. Accessed December 16, 2024. https://ir.darebioscience.com/news-releases/news-release-details/dare-bioscience-announces-publication-sexual-medicine-positive

3. Daré Bioscience announces phase 3 plans for sildenafil cream, 3.6%, in the treatment of female sexual arousal disorder (FSAD). News release. Daré Bioscience, Inc. Published online and accessed December 16, 2024. https://ir.darebioscience.com/news-releases/news-release-details/dare-bioscience-announces-phase-3-plans-sildenafil-cream-36