Vaginal tamoxifen capsule, potential new hormone-free treatment for women with postmenopausal vulvovaginal atrophy
USA: Vaginal tamoxifen capsule (DARE-VVA1) is safe, and results in minimal systemic exposure to tamoxifen in postmenopausal women with moderate to severe vulvovaginal atrophy (VVA), a phase 1/2 clinical study has shown. The findings were published in the International Menopause Society's journal, Climacteric.
DARE-VVA1, a vaginal tamoxifen capsule (Daré Bioscience), is a soft gelatin capsule containing tamoxifen for vulvovaginal atrophy treatment without hormones in postmenopausal women. Daré is developing DARE-VVA1 as a hormone-free alternative to estrogen-based therapies for treating moderate to severe VVA.
"The data from the study demonstrated safety and tolerability of our investigational product DARE-VVA1, as well as showed an improvement in vaginal cytology parameters and the bothersome vaginal symptoms commonly associated with vulvovaginal atrophy." Andrea Thurman, MD, medical director for Daré Bioscience, said in a related press release.
The team led by Dr Thurman set out to measure the safety, systemic pharmacokinetics and preliminary efficacy of DARE-VVA1 among postmenopausal women with moderate-to-severe vulvovaginal atrophy.
The researchers enrolled 17 postmenopausal women with moderate to severe vulvovaginal atrophy in the randomized, placebo-controlled, double-masked, phase 1/2 study of DARE-VVA1. They were randomly assigned to DARE-VVA1 at 1 mg (n = 3), 5 mg (n = 4), 10 mg (n = 3) and 20 mg (n = 3). 14 women completed the 8-week treatment. DARE-VVA1 was self-administered once daily for the first two weeks and then twice weekly for the remaining six weeks.
The authors reported the following findings:
- DARE-VVA1 was safe. All adverse events were of mild or moderate severity and distributed similarly among active and placebo groups.
- Plasma tamoxifen concentrations were highest among women using DARE-VVA1 20 mg, but the maximum mean (standard deviation) plasma tamoxifen concentrations on day 1 (2.66 ± 0.85 ng/ml) and day 56 (5.69 ± 1.87 ng/ml) were <14% of those measured after one oral tamoxifen dose.
- Active study product users had significant decreases from the pre-treatment baseline in vaginal pH and proportion of vaginal parabasal cells, with women randomized to the 10 mg or 20 mg dose experiencing the most considerable treatment impact.
- The severity of vaginal dryness and dyspareunia decreased significantly from baseline with active study product use.
"The unmet need for an effective non-hormonal treatment for VVA caused by anti-cancer endocrine therapy in patients diagnosed with HR+ breast cancer is undeniable," Sabrina Martucci Johnson, president and CEO of Daré Bioscience, said in the release.
"The current lineup of estrogen-based therapies, commonly used to treat VVA in non-cancer patients, can be challenging for both HR+ breast cancer patients and their providers as the use of estrogen products, in any form, is often contraindicated for the HR+ breast cancer patient population. "If we are successful, vaginally-administered, hormone-free DARE-VVA1 will offer patients and providers an important new treatment option to address one of the most common vaginal side effects associated with breast cancer therapy."
Reference:
A. Thurman, L. Hull, B. Stuckey, J. Hatheway, C. Mauck, N. Zack & D. Friend (2023) Pharmacokinetics, safety and preliminary pharmacodynamic evaluation of DARE-VVA1: a soft gelatin capsule containing tamoxifen for the treatment of vulvovaginal atrophy, Climacteric, DOI: 10.1080/13697137.2023.2211763
