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"Vaginal dryness is a very painful, day to day, quality of life concern for over 50% of menopausal women. The only available FDA-approved treatment for women is estrogen, which has been proven to increase the risks for a number of potentially fatal diseases including breast and uterine cancers, heart disease, stroke and blood clots. Considering the lack of safe treatment options for this indication, and given the data Bionovo has developed on this drug candidate, VG101 could be a superior treatment for the millions of women who want to improve both their quality of life as well as sexual functioning."

–Wulf Utian, M.D., Ph.D., D.Sc.
Founder and President Emeritus of the North American Menopause Society

 

 

Download the FDA Industry Guidance for the Development Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms

Seala® for Postmenopausal Vaginal Atrophy and Dryness

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Background

Vaginal atrophy is a frequent complaint of postmenopausal women that leads to symptoms of vaginal dryness, itching, discomfort and painful intercourse. Unlike other menopausal symptoms such as hot flashes and night sweats, symptoms of vaginal atrophy persist for decades after women cease to have regular menstrual cycles. Epidemiologic studies suggest that vaginal dryness affects approximately 40% of perimenopausal women and 55% of postmenopausal women.

Until very recently, postmenopausal estrogen replacement was widely used to treat vaginal dryness and other symptoms associated with urogenital atrophy.  Systemic estrogen preparations, such as oral estrogen pills and transdermal estrogen patches known as hormone therapies, were favored by those seeking to alleviate other menopausal symptoms such as hot flashes or to prevent postmenopausal bone density loss. Over the past decade, however, randomized clinical trials have conclusively shown that systemic estrogen replacement increases the risks of cardiovascular disease, venous thromboembolic events, breast cancer, uterine cancer and dementia. Furthermore, estrogen replacement appears to increase the risk of other urogenital problems, such as urinary incontinence, that are already widespread in older women with vaginal atrophy.  In the Women’s Health Initiative study, women taking unopposed estrogen had a 52% higher risk of developing urinary incontinence compared to placebo, and women taking combined estrogen plus progestin had a 39% higher risk compared to placebo.

Vaginal estrogen therapies in the form of creams, vaginal rings, and slow-release vaginal tablets have also been used to treat vaginal dryness, however systemic absorption of estrogen still occurs with vaginal estrogen administration, especially at the beginning of treatment when the vaginal epithelium is thin and atrophic. Therefore, risks associated with systemic estrogen therapy may also exist with the local application of estrogen therapy for vaginal atrophy.

Due to concerns about the side effects of systemic and local estrogen therapy, there is growing interest in new treatments for vaginal dryness. Bionovo recognizes this unmet need and is developing Seala, a non-steroidal vaginal suppository selective to the estrogen receptor beta (ERβ), to treat the symptoms associated with vaginal atrophy.

Seala Mechanism of Action

Bionovo’s strategy is to improve the treatment of menopausal symptoms by discovering safer compounds that are more selective to one of the two know estrogen receptor subtypes. All currently available estrogens contained in hormone therapy (HT) and the two FDA-approved SERMs (raloxifene and tamoxifen) regulate both ERα and ERβ. The lack of ER-subtype selectivity may contribute to some of the unwanted adverse clinical effects seen after initiating these FDA-approved therapies. Our objective is to discover safer, more selective drugs. Seala selectively targets ERβ and we have previously shown that ERβ acts as a tumor suppressor, inhibiting the proliferative effects mediated through ERα in breast cancer and uterine cell lines. The vaginal canal expresses both estrogen receptors, ERα and ERβ. In animal models, our estrogen receptor beta selective drug, Seala, was effective at treating vaginal atrophy without causing any untoward cancerous effects in the uterus.

Next Steps-Phase 1/2 Clinical Trial

A Phase 1/2 trial is expected to start soon. Enrollment for participation in the clinical trial will take place at the University of California, San Francisco and the University of Alabama, Birmingham.

Clinical Trial Design

In accordance with the FDA Guidance for Industry:Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms- Recommendations for Clinical Evaluation, Bionovo will conduct a prospective, randomized, blinded, placebo-controlled, dose escalation clinical trial in 4 cohorts of 10 postmenopausal women (total N=40) aged 45 to 65 years with at least one moderate to severe menopausal vaginal symptom, vaginal pH > 5.0 and ≤ 5% superficial vaginal epithelial cells, to determine the optimal dose of Seala for the treatment of vaginal atrophy based on the highest of 4 proposed dose levels during 12 weeks of treatment.

About Dr. Wulf H. Utian, the Clinical Trial Principle Investigator

Dr. Wulf H. Utian is a key opinion leader in the field of gynecological endocrinology, having studied the metabolic and psychosocial aspects of estrogen and menopause for over 30 years. Dr. Utian is currently President of Rapid Medical Research, Inc. and Founder and Executive Director of The North American Menopause Society (NAMS). Dr. Utian is also the Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology, Case Western Reserve University.

Dr. Utian is a member of numerous professional societies, both in the United States and abroad, and serves on a number of national and international committees, including the Board of Trustees of The North American Menopause Society and the Medical Health Advisory Board of the Society for Women's Health Research. He is Chairman of the Council of Affiliated Menopause Societies (CAMS), the policy-making organ of the International Menopause Society.

Over the course of his career, Dr. Utian has written over 190 papers related to the reproductive system in women and has authored five books on menopause and its effects on women. He is editor of both Menopause: The Journal of The North American Menopause Society and Menopause Management. He has served as an advisor to the Office of Technology Assessment (U.S. Federal Government) on menopause and testified before Congress on women's health issues. He is the Honorary Past President of the International Menopause Society and the Honorary Founding President of The North American Menopause Society. He serves on the editorial review boards of multiple professional publications.