Daré Bioscience Announces Additional Positive Data From Phase 2b Study of Sildenafil Cream in Women & Proposed Endpoints & Patient Population for Phase 3 Program

Daré Bioscience, Inc. and its collaborator Strategic Science & Technologies, LLC (SST), a Cambridge, MA-based novel topical drug delivery company, recently announced additional positive findings based on further analyses of data from the exploratory Phase 2b RESPOND study that evaluated Sildenafil Cream, 3.6% in women with female sexual arousal disorder (FSAD).

The Phase 2b RESPOND study enrolled women with FSAD and included women who had sexual dysfunctions in addition to FSAD. Further analyses of Phase 2b RESPOND study data identified a subset of study participants—women with FSAD as well as women with FSIAD whose primary complaint was arousal dysfunction—that achieved statistically significant and clinically meaningful improvement in the Phase 2b co-primary endpoint of evaluating the efficacy of Sildenafil Cream versus placebo cream as measured by change from baseline to the end of the 12-week double-blind dosing period in the Arousal-Sensation Domain of the Sexual Function Questionnaire (p=0.04). In addition, only the Sildenafil Cream treatment group in this subset, and not the placebo group, demonstrated clinically meaningful improvement at the end of the 12-week period.

The other co-primary objective of the Phase 2b RESPOND study was to evaluate the efficacy of Sildenafil Cream compared to placebo cream as measured by the change from baseline to the end of the 12-week double-blind dosing period in the score for feeling concerned by difficulties with sexual arousal utilizing the Female Sexual Distress Scale – Desire, Arousal, Orgasm (FSDS-DAO). Analyses of the same subset of women in the Phase 2b RESPOND study (women with FSAD and women with FSIAD whose primary complaint was arousal dysfunction) demonstrated that the Sildenafil Cream treatment group achieved statistically significant improvement in several FSDS-DAO questions, including regarding guilt, stress, inadequacy, and embarrassment due to their sexual problems (p=0.02 to 0.05).

“After showing improvements in multiple aspects of the sexual experience, we believe further analyses of the Phase 2b RESPOND study data support advancing the Phase 2b co-primary endpoints to our Phase 3 program and evaluating the efficacy of Sildenafil Cream in a broader population of women—women with FSAD and FSIAD,” said Sabrina Martucci Johnson, President and CEO of Daré Bioscience. “The further analyses bolster our belief that Sildenafil Cream has the potential to successfully address the significant unmet need of arousal disorder. We remain on track for an end of Phase 2 meeting to discuss these exciting findings with the FDA this year, and look forward to potentially initiating the first ever Phase 3 pivotal study for the treatment of arousal disorder in women. We also look forward to presenting these additional positive analyses at the upcoming meeting of the Sexual Medicine Society of North America in San Diego later this month.”

Based on data from the exploratory Phase 2b RESPOND study, demonstrating improvement in multiple facets of female sexual dysfunction, and because there is no FDA-approved product for FSAD, as described in the fourth edition of the Diagnostic and Statistical Manual (DSM-IV), or for FSIAD, as described in the fifth edition of the Diagnostic and Statistical Manual (DSM-5), Sildenafil Cream has the potential to be a first-in-category product.

The Phase 2b RESPOND study was a first of its kind Phase 2b clinical study that included patient reported outcome (PRO) instruments to screen eligible women and a number of primary, secondary, and exploratory PRO assessments to measure improvement in localized genital sensations of arousal and reduction in the distress that women experience with FSAD. There are no FDA-approved treatments for FSAD or FSIAD and thus there are no efficacy endpoints that have been previously validated in Phase 3 pivotal studies for potential treatments for FSAD or FSIAD. The Phase 3 study design for Sildenafil Cream, including primary and secondary efficacy endpoints and inclusion/exclusion criteria for study participants, will be determined following discussions with the U.S. Food and Drug Administration (FDA), including the company’s end of Phase 2 meeting with the FDA.

FSAD, as described in the DSM-IV, is a condition characterized as primarily by a persistent or recurrent inability to attain or maintain sufficient genital arousal (an adequate lubrication-swelling response) during sexual activity, frequently resulting in distress or interpersonal difficulty, and, of the various types of female sexual dysfunction disorders, FSAD is most analogous to erectile dysfunction (ED) in men. As with ED in men, FSAD is associated with insufficient blood flow to the genitalia.

FSIAD is characterized in the DSM-5 as lack of, or significantly reduced, sexual interest and/or arousal for at least six months and the symptoms must be severe enough to cause clinically significant distress. A woman must have three of the following six symptoms in order to receive an FSIAD diagnosis: absent or reduced interest in sexual activity; absent or reduced sexual thoughts or fantasies; no or reduced initiation of sexual activity, and typically unreceptive to a partner’s attempts to initiate; absent or reduced sexual excitement or pleasure in almost all or all sexual encounters; absent or reduced sexual interest/arousal in response to any internal or external sexual cues; and absent or reduced genital or non-genital sensations during sexual activity in all or almost all sexual encounters. FSIAD can be lifelong or acquired, range from mild to severe, and may be generalized or situational.

Sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, is the active ingredient in a tablet for oral administration currently marketed under the brand name Viagra for the treatment of ED in men. Sildenafil Cream is an investigational, proprietary cream formulation of sildenafil designed for topical administration to the vulvar-vaginal tissue on demand to increase genital blood flow and provide improvements in the female genital arousal response, while avoiding systemic side effects observed with oral formulations of sildenafil.

Market research suggests that 16% of women in the US ages 21 to 60, or approximately 10 million women, are distressed from experiencing symptoms associated with FSAD, including lack of or low sexual arousal, and are actively seeking solutions to improve their condition. In comparison, the prevalence of complete ED in men is estimated to be about 5% of men at age 40, increasing to about 15% at age 70.

Daré Bioscience is a biopharmaceutical company committed to advancing innovative products for women’s health. The company’s mission is to identify, develop and bring to market a diverse portfolio of differentiated therapies that prioritize women’s health and well-being, expand treatment options, and improve outcomes, primarily in the areas of contraception, vaginal health, reproductive health, menopause, sexual health and fertility.

Daré’s first FDA-approved product, XACIATO (clindamycin phosphate) vaginal gel 2% is a lincosamide antibacterial indicated for the treatment of bacterial vaginosis in female patients 12 years of age and older, which is under a global license agreement with Organon. Daré’s portfolio also includes potential first-in-category candidates in clinical development: Ovaprene, a novel, hormone-free monthly intravaginal contraceptive whose US commercial rights are under a license agreement with Bayer; Sildenafil Cream, 3.6%, a novel cream formulation of sildenafil to treat female sexual arousal disorder (FSAD) and/or female sexual interest/arousal disorder (FSIAD) utilizing the active ingredient in Viagra; and DARE-HRT1, a combination bio-identical estradiol and progesterone intravaginal ring for menopausal hormone therapy. For more information, visit www.darebioscience.com.