Daré Bioscience Initiates Phase 1/2 Clinical Study of DARE-VVA1, Intravaginal Tamoxifen for the Treatment of Vulvar & Vaginal Atrophy

Daré Bioscience, Inc. recently announced the initiation of a Phase 1/2 clinical study of DARE-VVA1, a novel intravaginal tamoxifen product being developed for the treatment of moderate to severe vulvar and vaginal atrophy (VVA). The randomized, double-blind, placebo-controlled study is designed to evaluate the safety, pharmacokinetics and pharmacodynamics of DARE-VVA1 in postmenopausal participants with moderate to severe VVA and is being conducted by the company’s wholly owned subsidiary in Australia.

“Vulvar and vaginal atrophy is an inflammation of the vaginal epithelium associated with lower estrogen levels as a result of menopause and certain cancer treatments and its symptoms adversely impact quality of life for women. Today, therapies for VVA are predominantly based on estrogen; however, there is a large unmet need for a novel non-hormonal VVA treatment specifically developed for women who have VVA as a result of treatment for hormone receptor-positive breast cancer, as well as for other women, who require or prefer a treatment option for VVA that does not contain estrogen,” said Sabrina Martucci Johnson, Daré’s President and Chief Executive Officer. “We’re encouraged by an exploratory study of intravaginally administered tamoxifen published in Clinical and Experimental Obstetrics and Gynecology , that demonstrated improvements in vaginal pH and vaginal dryness without significant systemic absorption of tamoxifen in postmenopausal women with VVA, together with studies of tamoxifen conducted over the last 40 years that have documented its estrogen-like effects on the vaginal epithelium. We’re excited for the clinical advancement of DARE-VVA1 as a potential non-hormonal treatment alternative for this population.”

The Phase 1/2 study will evaluate different doses of DARE-VVA1, a tamoxifen vaginal insert, in approximately 40 postmenopausal women with VVA, including a cohort of women with a history of breast cancer. The study is a randomized, multi-center, double-blind, parallel-arm, placebo-controlled, dose‑ranging study that will evaluate the safety, tolerability, plasma pharmacokinetics (PK) and pharmacodynamics (PD) of DARE‑VVA1. Eligible participants will be randomly allocated to one of five treatment groups (approximately 8 participants per group) that will evaluate four dose levels (1 mg, 5 mg, 10 mg, and 20 mg) and a placebo. Following a screening visit, DARE‑VVA1 will be self-administered intravaginally once a day for the first 2 weeks, and then twice a week for the following 6 weeks for a total treatment period of 56 days. In each treatment group, participants will have serial blood sampling for PK analysis and undergo safety evaluations and preliminary assessments of effectiveness. Following the completion of the treatment period, participants will attend a safety follow-up visit.

The primary endpoints of the study will evaluate the safety and tolerability of DARE-VVA1 by vaginal administration and determine the plasma PK of DARE-VVA1 after intravaginal application. Secondary endpoints will evaluate preliminary efficacy and PD of DARE-VVA1 in terms of most bothersome symptom and changes in vaginal cytology and pH.

“Women navigating breast cancer treatment face many challenges and hardships in addition to those we commonly think about, including VVA,” said James A. Simon, MD, CCD, NCMP, IF, FACOG, Clinical Professor of Obstetrics and Gynecology at The Washington University School of Medicine, and Medical Director and Founder of IntimMedicine Specialists. “Having a safe and effective, non-hormonal therapy to address the uncomfortable symptoms of VVA could offer both physical and psychological benefits to patients and survivors. I look forward to following the progression of DARE-VVA1 as a potential first-in-category hormone-free vaginal treatment for VVA.”

VVA is an inflammation and thinning of the vaginal epithelium due to the reduction in levels of circulating estrogen. Typical symptoms include vaginal dryness, itching, burning, and painful intercourse, adversely impacting quality of life. VVA is a common condition in postmenopausal women and women with, or with a history of, hormone receptor-positive (HR+) breast cancer. Many breast cancer survivors experience menopausal symptoms irrespective of age as a direct consequence of their cancer treatment. Breast cancer patients treated with aromatase inhibitors refer to VVA as one of the most unpleasant side effects of treatment. Approximately 10% of women in the US will develop breast cancer. The prevalence of VVA in postmenopausal breast cancer patients is estimated to be between 42% and 70%.

Products containing estrogen are commonly used to treat VVA. However, the use of estrogen-containing products for the treatment of VVA may be contraindicated for HR+ breast cancer patients and survivors because of the concern that estrogen use will promote recurrence of disease.

DARE-VVA1 is an investigational, proprietary formulation of tamoxifen for intravaginal administration with the potential to be a first-in-category treatment of VVA for women with or at-risk of HR+ breast cancer. Tamoxifen is a well-known and well-characterized selective estrogen receptor modulator (SERM) that has been prescribed by oncologists for decades for the treatment of breast cancer. In breast tissue, tamoxifen acts as an estrogen antagonist. In contrast, in other tissues such as vaginal tissues, tamoxifen has been reported to exert an estrogen-like response on vaginal cytology. Studies of tamoxifen conducted over the last 40 years have documented its estrogen-like effects on vaginal epithelium. Localized tamoxifen therapy such as DARE-VVA1 thus has the potential to counter the physiologic changes that lead to VVA without introducing estrogen back into the system.

Daré Bioscience is a clinical-stage biopharmaceutical company committed to the advancement of 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 expand treatment options, improve outcomes and facilitate convenience for women, primarily in the areas of contraception, vaginal health, sexual health, and fertility. Daré’s product portfolio includes potential first-in-category candidates in clinical development: Ovaprene, a novel, hormone-free monthly contraceptive whose U.S. 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 utilizing the active ingredient in Viagra; DARE-BV1, a unique hydrogel formulation of clindamycin phosphate 2% to treat bacterial vaginosis via a single application; and DARE-HRT1, a combination bio-identical estradiol and progesterone intravaginal ring for hormone therapy following menopause. For more information, visit www.darebioscience.com.