Daré Bioscience, Inc. recently announced the publication of positive preliminary efficacy results from its Phase 1/2 clinical study of DARE-HRT1 in healthy postmenopausal women. DARE-HRT1, an investigational ethylene vinyl acetate copolymer intravaginal ring (IVR) designed to release bio-identical 17β2-estradiol and progesterone over 28 days as part of a hormone therapy regimen, is part of Daré’s proprietary IVR technology platform originally developed by Dr. Robert Langer from the Massachusetts Institute of Technology and Dr. William Crowley from Massachusetts General Hospital and Harvard Medical School. DARE-HRT1 is being developed for the treatment of moderate-to-severe VMS due to menopause in women with intact uteri.

The journal article, titled A phase 1/2, open-label, parallel group study to evaluate the preliminary efficacy and usability of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women, is available online through both the Latest Articles section of the Menopause journal’s website, as well as the Scientific & Clinical Publications section of Daré’s website, and will be published in Volume 30, Issue 9 of Menopause. The article reports the results of the exploratory objectives of the Phase 1/2 study, which included assessing the usability, acceptability and preliminary efficacy of two dose configurations of DARE-HRT1. The results of the primary objectives of the study, which were to evaluate the safety and pharmacokinetics (PK) of the two dose configurations of DARE-HRT1, are described in a separate article published in an earlier issue of Menopause..

“More women are looking for options to manage their moderate-to-severe vasomotor symptoms that are commonly associated with menopause. We are encouraged by the findings from this study as we believe DARE-HRT1 has the ability to address a persistent unmet medical need,” said Andrea Thurman, MD, Medical Director for Daré Bioscience and lead author of the journal article. “In this study, preliminary VMS treatment efficacy was supported by significant decreases from baseline in all domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire for both dosing groups (p<0.01), indicating improvement in the overall MENQOL score and in all MENQOL domains, and preliminary local GSM treatment efficacy was supported by significant improvement in vaginal cytology parameters for both dosing groups and improvement in bothersome vaginal symptoms commonly associated with GSM.”

“Data from this study support further development of DARE-HRT1 as a potential first-in-category product to offer bio-identical estradiol and bio-identical progesterone therapy in a convenient monthly, non-oral format, consistent with NAMS guidance for delivering both hormones, together,” said Sabrina Martucci Johnson, President and CEO of Daré Bioscience. “We look forward to advancing DARE-HRT1 into a single Phase 3 pivotal clinical trial to support a new drug application for the treatment of moderate-to-severe VMS due to menopause in women with intact uteri.”

Hormone therapy is recommended as a first-line, effective treatment for the management of VMS and GSM among healthy postmenopausal women by the American College of Obstetricians and Gynecologists, the International Menopause Society, and NAMS. NAMS’ guidance on hormone therapy states that dosing estrogen and progestogen in combination may offer important benefits to women with an intact uterus, and NAMS observed that non-oral routes of administration may offer advantages over orally administered therapies because nonoral routes bypass the first-pass hepatic effect.

Menopause is defined as the final menstrual period and is typically confirmed after a woman has missed her period for 12 consecutive months. Most women experience menopause between ages 40 and 58.1 Over 45 million women in the US are estimated to be approaching or in menopause, which results in a decrease in estrogen and other hormones. Hot flashes, vaginal dryness and loss of bone density are frequently associated with menopause. Night sweats (hot flashes that occur during sleep) often cause sleep disturbance, and vaginal atrophy (the drying and thinning of vaginal tissues) can cause a feeling of vaginal tightness during sex along with pain, burning, or soreness. Hence, management of menopausal symptoms can impact quality of life, productivity and health. NAMS believes that hormone therapy is the most effective treatment for VMS and GSM and observes that a non-oral route may offer potential advantages over oral routes of administration.

Following clinical development, Daré intends to leverage the existing safety and efficacy data on the active ingredients in DARE-HRT1, estradiol and progesterone, to utilize the US FDA’s 505(b)(2) pathway to obtain marketing approval of DARE-HRT1 in the US.

Daré intends to seek FDA approval of DARE-HRT1 for the treatment of moderate-to-severe VMS due to menopause in women with intact uteri. Based on pre-IND communications with the FDA and the topline PK data from the DARE-HRT1 Phase 1/2 study, Daré believes FDA approval of DARE-HRT1 for that indication is achievable via the 505(b)(2) pathway supported by a single, placebo-controlled, Phase 3 clinical trial of DARE-HRT1 and a scientifically justified PK “bridge” (via a relative bioavailability trial) between DARE-HRT1 and the selected listed estradiol and progesterone drugs. Ongoing activities to support progressing directly into a single Phase 3 study to support registration include manufacturing and non-clinical studies to support the Investigational New Drug Application (IND) submission and the planned IND-opening Phase 3 study.

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.