Daré Bioscience Announces Positive Topline Data from the Exploratory Phase 2b RESPOND Study of Sildenafil Cream, 3.6% in Women with Female Sexual Arousal Disorder

Sildenafil Cream-treated patients showed meaningful improvement in the co-primary endpoint assessment that evaluated change from baseline in the Arousal-Sensation Domain of the Sexual Function Questionnaire

Sildenafil Cream-treated patients also showed improvements in the secondary endpoint and pre-specified exploratory endpoints that evaluated sexual satisfaction, arousal lubrication, and achievement and pleasure of orgasm

Data support continued development of Sildenafil Cream and selection of proposed primary endpoint assessments for a Phase 3 study

Sildenafil Cream has the potential to be the first FDA-approved treatment for female sexual arousal disorder

SAN DIEGO, June 05, 2023 (GLOBE NEWSWIRE) -- Daré Bioscience, Inc. (NASDAQ: DARE), a leader in women’s health innovation, and its collaborator Strategic Science & Technologies, LLC (SST), a Cambridge, MA based novel topical drug delivery company, today announced positive topline data from the exploratory Phase 2b RESPOND study evaluating topical Sildenafil Cream, 3.6% (Sildenafil Cream) as a treatment for female sexual arousal disorder (FSAD). The exploratory study was designed to test the sensitivity of several patient reported outcome (PRO) efficacy endpoints and their ability to determine a treatment effect of Sildenafil Cream compared to placebo to inform the ongoing development of Sildenafil Cream. The study also served as a validation study of exploratory endpoints that could be candidate endpoints in a Phase 3 study of Sildenafil Cream. Although the exploratory study was underpowered to assess statistical significance, certain endpoints achieved statistical significance.

FSAD is the inability to reach or maintain a sufficient physical response to sexual stimulation and, of the various types of female sexual dysfunction disorders, FSAD is most analogous to erectile dysfunction (ED) in men. 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 topical cream formulation of sildenafil specifically designed to increase blood flow to the genital tissue in women. If development is successful, Sildenafil Cream has the potential to be the first FDA-approved treatment for FSAD. Market research suggests that 16% of women in the U.S. 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.

“We are very pleased with the topline data from the Phase 2b RESPOND study. Although the study was underpowered to assess statistical significance, we saw statistically significant results for certain of the endpoints, and the data indicate that, as compared to placebo, Sildenafil Cream had a therapeutic effect based on several PROs,” said Sabrina Martucci Johnson, President and CEO of Daré Bioscience. “Because there are currently no FDA-approved treatments for FSAD, there are no efficacy endpoints that have been previously approved for use in a Phase 3 pivotal study for potential treatment for FSAD – but with the data from the Phase 2b RESPOND study we believe certain of the primary, secondary, and exploratory endpoints could be candidate endpoints in a Phase 3 study of Sildenafil Cream. Having now completed this pioneering work in the field of FSAD, we look forward to reviewing the data with the FDA, including discussing the data from assessments as early as the 4- and 8-week mark after randomization, and continuing the development of Sildenafil Cream, including our objective of initiating the first ever Phase 3 pivotal study for the treatment of FSAD. Following clinical development, Daré intends to leverage the existing safety and efficacy data on the active ingredient in Sildenafil Cream to utilize the FDA’s 505(b)(2) pathway to obtain marketing approval of Sildenafil Cream in the U.S.”

"The FDA has not approved any pharmacologic options for FSAD, a condition which significantly compromises a woman's ability to have a pleasurable sexual experience," commented Dr. Sheryl Kingsberg, Division Chief of Behavioral Medicine, Department of OBGYN, University Hospitals Cleveland Medical Center, Ohio, and Past President of The International Society for the Study of Women's Sexual Health, as well as co-editor of the Textbook of Female Sexual Function and Dysfunction: Diagnosis and Treatment. "Based on the topline data from the Phase 2b RESPOND study I am very excited about the potential for this topical Sildenafil Cream to address this critical unmet need in women's sexual health. Leveraging the known therapeutic benefit of the active ingredient in Viagra®, sildenafil, in a cream formulation to stimulate increased blood flow to the genital tissue, Sildenafil Cream may offer women a safe, effective and ‘on demand' solution to difficulties with sexual arousal allowing for a more intense and enjoyable sexual experience."

Unlike the oral formulations of PDE-5 inhibitors, Sildenafil Cream is designed to be applied locally to the vulvar-vaginal tissue prior to sexual activity to facilitate vasodilation and increase blood flow directly to the genital tissue to improve the physical arousal response to address the lack of those genital arousal sensations commonly associated with FSAD. Increasing blood flow to the genital tissue, as Sildenafil Cream is designed to do, has the potential to improve genital arousal response and overall sexual experience for women. This is similar to the way ED medications work in men by directing blood flow to the genitals when taken prior to sexual activity.

“The topline data from the Phase 2b RESPOND study represent an important milestone in the field of female sexual dysfunction,” said Dr. Andrew Goldstein, Medical Advisor of Daré Bioscience and Past President of The International Society for the Study of Women's Sexual Health, as well as co-editor of the Textbook of Female Sexual Function and Dysfunction: Diagnosis and Treatment. “It is exciting to be working at the cutting edge of research focused on women’s sexual health and to advance a potential first-in-category treatment option for women suffering with FSAD.”

“It is encouraging to see sponsors such as Daré and SST developing endpoints that will foster approval of new medicines for women in FSAD. The previously completed content validation study and the exit interviews completed as part of the Phase 2b RESPOND study are significant steps to gaining regulatory approval of endpoints in this area. I look forward to continuing our collaboration by using the Phase 2b RESPOND study data to conduct psychometric analyses to further refine the measures and resulting endpoints for use in a Phase 3 pivotal study,” said Tara Symonds, Ph.D., Managing Director, UK, and Chief Scientific Officer at Clinical Outcomes Solutions, who is an advisor to Daré and SST and has extensive expertise in the development and validation of PROs for sexual health clinical trials, including establishing and leading Pfizer’s PRO Center of Excellence earlier in her career.

Daré plans to submit data from the Phase 2b RESPOND clinical study of Sildenafil Cream for publication in a peer-reviewed journal.

About the Exploratory Phase 2b RESPOND Study

Study Design

The exploratory Phase 2b RESPOND study was a multi-center, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of Sildenafil Cream in premenopausal patients with FSAD. The study was a first of its kind Phase 2b clinical study that includes PRO instruments to screen eligible women with FSAD and included two co-primary endpoints, a secondary endpoint, and a number of exploratory endpoints to measure, among other things, improvement in localized genital sensations of arousal, reduction in the distress that women experience with FSAD and satisfactory sexual events. There are no FDA-approved treatments for FSAD and thus there are no efficacy endpoints that have been previously validated in a Phase 3 pivotal study for potential treatments for FSAD.

The FDA requested that any PROs for use in the assessment of efficacy in a Phase 3 study be adequately validated. Part of that validation of the PROs includes exit interviews performed as part of the Phase 2b RESPOND study to better understand qualitatively what constitutes a meaningful change to the subjects. These qualitative assessments of meaningful change were utilized to determine which endpoints achieved meaningful improvement in the Sildenafil Cream group. Additional psychometric analyses using the Phase 2b RESPOND study dataset is planned to further refine and validate the measures to inform the most appropriate endpoints for use in a Phase 3 pivotal study.

The Phase 2b RESPOND study began with 99 subjects in the Sildenafil Cream intent to treat population and 93 subjects in the placebo intent to treat population, with 70 subjects in the Sildenafil Cream intent to treat population and 60 subjects in the placebo intent to treat population completing the study, and therefore was underpowered to assess statistical significance. During the study, participants used Sildenafil Cream and a placebo cream in their home setting and documented their experience using PRO instruments. The study evaluated Sildenafil Cream compared to placebo cream over 12 weeks of dosing following both a non-drug and placebo run-in period.

Study Efficacy Results and Safety

Summary of Topline DataA co-primary endpoint of the Phase 2b RESPOND study was to evaluate the efficacy of Sildenafil Cream compared to placebo as measured by change from baseline to the end of the study in the Arousal-Sensation Domain of the 28-item Sexual Function Questionnaire (SFQ28). The endpoint did not achieve statistical significance. However, the change at the end of the study in the group treated with Sildenafil Cream was consistent with how women reported meaningful improvement in an exit interview at the end of the study.

The other co-primary endpoint was to evaluate the efficacy of Sildenafil Cream compared to placebo as measured by change from baseline to the end of the study in the score for feeling concerned by difficulties with sexual arousal. The change was assessed using the previously validated Female Sexual Distress Scale – Desire, Arousal and Orgasm (FSDS-DAO) Survey. This assessment did not differentiate Sildenafil Cream from placebo.

The secondary endpoint of the study was to evaluate the efficacy of Sildenafil Cream compared to placebo as measured by change from baseline to the end of the study in the number of satisfactory sexual events based on the subjects’ response to a question answered and recorded via electronic diary within 24 hours after each sexual event. The endpoint was selected because it can serve as a primary endpoint in a Phase 3 study based on the FDA draft 2016 guidance document for female sexual dysfunction. When measured at the 4- and 8-week mark after randomization, subjects treated with Sildenafil Cream had a higher proportion of satisfying sexual events during the prior month (68.6% and 74.1% at the 4- and 8-week mark, respectively) compared to those treated with placebo (47.9% and 67.9% at the 4- and 8-week mark, respectively) (week 4 P value = 0.04).

The exploratory endpoints (selected based on the Content Validity study conducted by SST and Daré) included endpoints related to genital arousal, genital blood flow, lubrication, orgasm, concerns about difficulties with sexual arousal, and other assessments including questions regarding satisfying sexual events. The exploratory endpoints were assessed at multiple periods over the course of the study via electronic diary.

• An exploratory endpoint regarding concerns about difficulties with sexual arousal differentiated Sildenafil Cream versus placebo. Specifically, when asked about their overall impression of change regarding their concerns about difficulties with sexual arousal, women treated with Sildenafil Cream were more likely to report an overall improvement. Based on responses to the question at the 4-, 8- and 12-week mark after randomization, 44% to 49% of the subjects treated with Sildenafil Cream reported an overall improvement compared to 37% to 44% of the subjects treated with placebo (P value < 0.01).
• Exploratory endpoints related to arousal lubrication and achievement and pleasure of orgasm also demonstrated important differences between the subjects treated with Sildenafil Cream compared to placebo as measured by change from baseline to the 8-week mark after randomization, at P value = 0.059 and P value = 0.066, respectively (trending toward significance despite the small number of subjects in each group, n=73 in the Sildenafil Cream intent to treat group and n=64 in the placebo intent to treat group for these assessments).
• 48.7% of the subjects treated with Sildenafil Cream reported an increase in their overall satisfaction with sexual activity measured at the end of the study, compared to 42.6% of the subjects treated with placebo.

Summary of Cited Top Line DataThe exploratory Phase 2b RESPOND study was underpowered to assess statistical significance, although statistical significance was achieved on certain assessments. The following table sets forth certain data regarding the co-primary endpoints, the secondary endpoint, and certain exploratory endpoints: