A new analysis of data from the phase 2b RESPOND trial indicates that the efficacy of topical sildenafil cream, 3.6%, for female sexual arousal disorder (FSAD) is consistent across different patient subgroups. The post-hoc analysis, published in Sexual Medicine, found that age, race, and hormonal contraceptive use did not significantly affect the cream's effectiveness in premenopausal women with FSAD.
The RESPOND trial, a phase 2b study (NCT04948151), enrolled 200 patients with FSAD across 49 clinical trial sites in the US. The intent-to-treat population included 192 patients who were randomized 1:1 to receive either topical sildenafil cream (n = 99) or a placebo cream (n = 93). The primary endpoints were changes 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). A secondary endpoint was the change from baseline to week 12 in the average number of satisfactory sexual events (SSEs) reported.
Subgroup Analysis Details
The post-hoc analysis explored the impact of several factors on the efficacy of sildenafil cream. According to the study, "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)."
Interestingly, within the sildenafil cream cohort, younger participants (18-45 years), non-White participants, and hormonal contraceptive users showed greater improvements in the SFQ28 AS domain compared to their counterparts. However, the researchers noted that formal statistical comparisons within these treatment groups were not pre-planned.
Impact of Psychiatric Medication
The analysis also revealed that daily psychiatric medication users in both the sildenafil and placebo groups reported decreases in SFQ28 Desire domain scores from baseline to week 12. In contrast, non-users of psychiatric medications in the sildenafil group reported an increase of 1.85 ± 0.55 in the SFQ28 Desire domain score, while those in the placebo group reported an increase of 0.52 ± 0.58. This difference, however, 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."
Effects on Satisfactory Sexual Events
Regarding the secondary endpoint, age and baseline hormonal contraceptive use did not significantly impact the change in the average number of SSEs from baseline to week 12 (all P values > .67). However, non-White participants receiving sildenafil cream reported an increase of 0.7 ± 0.63 SSEs at week 12, while those receiving placebo cream reported a decrease of 1.5 ± 0.58 SSEs (P = .02).
Path to Phase 3
Based on these findings, Daré Bioscience is moving forward with plans to initiate a phase 3 trial of sildenafil cream, 3.6%, for FSAD. The company intends to submit its protocol and analysis plan to the FDA in Q1 2025, with the phase 3 trial expected to commence 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. "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."
Daré Bioscience anticipates that a second confirmatory phase 3 trial will be necessary to support a New Drug Application submission to the FDA for sildenafil cream, 3.6%.
