Full Press Release Details
Bioscience Announces Positive Topline Results from DARE-VVA1 Phase 1/2 Clinical Study
Demonstrated Improvement in Vaginal Cytology Parameters and Bothersome Symptoms of Vulvar and Vaginal Atrophy (VVA), Supporting Ongoing
Therapy for Women with VVA Who Cannot, or Should Not, Take Supplemental Estrogen, Including Women with Hormone Receptor-Positive (HR+)
are Currently No FDA-Approved Products Labeled for VVA Treatment for Patients with or at Risk of Recurrence of HR+ Breast Cancer
DIEGO, November 14, 2022 (GLOBE NEWSWIRE) -- Dar Bioscience, Inc. (NASDAQ: DARE), a leader in women's health
innovation, today announced topline data from its Phase 1/2 clinical study of DARE-VVA1, a novel intravaginal proprietary formulation
of tamoxifen being developed for the treatment of moderate to severe vulvar and vaginal atrophy. The randomized, double-blind, placebo-controlled
study was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of DARE-VVA1 in postmenopausal participants
with moderate to severe VVA. The topline data from the study demonstrated safety and tolerability of DARE-VVA1, as well as improvement
in the vaginal cytology parameters and the bothersome vaginal symptom associated with VVA. DARE-VVA1 has the potential to be the first
therapeutic specifically approved for the treatment of VVA in U.S. patients with HR+ breast cancer. There are currently no FDA-approved
products labeled for VVA treatment in HR+ breast cancer patients.
breast cancer is the most frequently diagnosed cancer type, accounting for over two million cases each year. Approximately 4 million
U.S. women have a history of invasive breast cancer, and of all breast cancer diagnoses in U.S. women, it is estimated that more than
68% are HR+. VVA prevalence in postmenopausal breast cancer survivors is estimated at 42% to 70%.
is a clear unmet need for an effective non-hormonal treatment for VVA caused by anti-cancer endocrine therapy in patients diagnosed with
HR+ breast cancer. Commonly, estrogen-based therapies delivered through creams, intravaginal rings, and vaginal suppositories are prescribed
for the treatment of VVA symptoms. However, the use of estrogen-based products for the treatment of VVA in HR+ breast cancer patients
can be challenging for both healthcare providers and their patients as the use of estrogen products, in any form, is often contraindicated
for this patient population," said Sabrina Martucci Johnson, President and Chief Executive Officer of Dar Bioscience. "If
we are successful, vaginally-administered DARE-VVA1 has the potential to become a new standard of care as the first and only product
approved in the U.S. for the treatment of VVA specifically in an HR+ breast cancer patient population."
are highly encouraged by the positive topline results of the Phase 1/2 study of DARE-VVA1 as this study is a critical step in developing
a potential non-hormonal treatment alternative for VVA," said Dr. Annie Thurman, Medical Director of Dar Bioscience. "The
symptoms of VVA adversely impact quality of life for women, particularly women also undergoing HR+ breast cancer treatment and management."
Phase 1/2 Clinical Trial Study Design
Phase 1/2 study evaluated different doses of DARE-VVA1, a tamoxifen vaginal insert, in 17 postmenopausal women with VVA. The study was
a randomized, multi-center, double-blind, parallel-arm, placebo-controlled, dose-ranging study that evaluated the safety, tolerability,
plasma pharmacokinetics (PK) and pharmacodynamics (PD) of DARE-VVA1. Eligible participants were randomly allocated to one of five treatment
groups (approximately 4 participants per group) that evaluated four dose levels (1 mg, 5 mg, 10 mg, and 20 mg)
and a placebo. Following a screening visit, DARE-VVA1 was self-administered intravaginally once a day for the first two weeks, and then
twice a week for the following six weeks for a total treatment period of 56 days. In each treatment group, participants had serial
blood sampling for PK analysis and underwent safety evaluations and preliminary assessments of effectiveness. Following the completion
of the treatment period, participants attended a safety follow-up visit.
primary endpoints of the study evaluated the safety and tolerability of DARE-VVA1 by vaginal administration and determined the plasma
PK of DARE-VVA1 after intravaginal application. Secondary endpoints evaluated preliminary efficacy and PD of DARE-VVA1 in terms of most
bothersome vaginal symptom and changes in vaginal cytology and pH.
study was conducted by the company's wholly owned subsidiary in Australia.
Results of the Phase 1/2 Clinical Trial
age of the 17 postmenopausal women with VVA who participated in the study ranged from 49 to 68 years (average age: 60.9). Fourteen women
completed the study.
primary outcomes of this first-in-woman study were safety and plasma PK. Intravaginal administration of DARE-VVA1 was well tolerated
and all treatment emergent adverse events were mild or moderate and equally distributed between participants randomized to study drug
treatment versus placebo. Concentration of tamoxifen in plasma samples collected over the course of the study did not exceed 10 ng/mL,
even in participants in the highest dose group (20 mg), which is 1/10th of the average steady-state concentration of tamoxifen seen with
daily dosing of orally administered tamoxifen citrate tablets (20 mg and 10 mg tamoxifen) for three months (average steady-state plasma
concentrations of over 100 ng/mL). Secondary outcomes of the study were preliminary efficacy and PD of DARE-VVA1 in terms of most bothersome
vaginal symptom and changes in vaginal cytology and pH. Participants who received study drug treatment (at 1 mg, 5 mg, 10 mg or 20 mg
doses) had improvements in the assessments and symptoms associated with VVA - specifically, they had decreases in vaginal pH, increases
in the percentage of vaginal superficial cells, significant (p=0.04) decreases in the percentage of vaginal parabasal cells (despite
the small sample size), and reduction in their self-assessed most bothersome vaginal symptom reported (either vaginal dryness or pain
the most bothersome vaginal symptom reported, of the participants randomized to receive study drug treatment, 39% (5/13) reported that
vaginal dryness and 62% (8/13) reported that pain with intercourse (dyspareunia) was their most bothersome vaginal symptom at baseline.
At the end of the treatment period, among the participants randomized to receive study drug treatment who reported vaginal dryness as
their most bothersome symptom at baseline (n=5) (moderate or severe), all those who completed the study reported that vaginal dryness
was either absent (n=1) or mild (n=3). Among the participants randomized to receive study drug treatment who reported dyspareunia as
their most bothersome symptom at baseline (n=8) (moderate or severe), at the end of the treatment period, four reported no longer experiencing
dyspareunia, one reported mild dyspareunia, two had no change in this symptom, and one did not complete the study. Of the four participants
randomized to the placebo group, two reported vaginal dryness and two reported dyspareunia as their most bothersome symptom at baseline.
At the end of the treatment period, the participants randomized to the placebo group who reported vaginal dryness as their most bothersome
symptom at baseline (n=2) (moderate or severe), reported that vaginal dryness was either absent (n=1) or mild (n=1), and among the participants
randomized to the placebo group who reported dyspareunia as their most bothersome symptom at baseline (n=2), one reported no longer experiencing
dyspareunia and one did not complete the study.
plans to submit data from the Phase 1/2 clinical study of DARE-VVA1 for publication in a peer-reviewed publication.
clinical development, Dar intends to leverage the existing safety and efficacy data on the active ingredient in DARE-VVA1, tamoxifen,
to utilize the U.S. Food and Drug Administration's (FDA) 505(b)(2) pathway to obtain marketing approval of DARE-VVA1 in the U.S.
Vulvar and Vaginal Atrophy (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, 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. The prevalence of VVA in postmenopausal breast cancer patients is estimated to be between
containing estrogen are commonly used to treat VVA. However, the use of estrogen-containing products for the treatment of VVA is often
contraindicated for HR+ breast cancer patients and survivors because of the concern that estrogen use will promote recurrence of disease.
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.
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, fertility, and vaginal and sexual
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. XACIATO
is a clear, colorless, viscous gel, to be administered once intravaginally as a single dose. Dar 's portfolio also includes
potential first-in-category candidates in clinical development: Ovaprene , a novel, hormone-free monthly intravaginal 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 ; and DARE-HRT1, a combination bio-identical estradiol
and progesterone intravaginal ring for hormone therapy following menopause. To learn more about XACIATO , Dar 's full
portfolio of women's health product candidates, and Dar 's mission to deliver differentiated therapies for women,
please visit www.darebioscience.com.
may announce material information about its finances, product and product candidates, clinical trials and other matters using the Investors
section of its website (http://ir.darebioscience.com), SEC filings, press releases, public conference calls and webcasts. Dar
will use these channels to distribute material information about the company, and may also use social media to communicate important
information about the company, its finances, product and product candidates, clinical trials and other matters. The information Dar
posts on its investor relations website or through social media channels may be deemed to be material information. Dar encourages
investors, the media, and others interested in the company to review the information Dar posts in the Investors section of its
website and to follow these Twitter accounts: @SabrinaDareCEO and @DareBioscience. Any updates to the list of social media channels the