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“Menerba provides a true paradigm shift in the treatment of menopausal hot flashes. The novel mechanism of action, the exciting preclinical and clinical safety, and the early efficacy are encouraging. I believe swift development is warranted so we can provide women with an alternative to hormone therapy.”  

–Wulf Utian, M.D., Ph.D., D.Sc.
Founder and President Emeritus of the
North American Menopause Society and Menerba’s Principal Clinical Investigator

 

 

 

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

Menerba® for the Treatment of Vasomotor Symptoms (Hot Flashes) Associated with Menopause

Menerba LogoBackground
Today, there are approximately 40 million American women transitioning through menopause. At least two thirds of these women will experience vasomotor symptoms, including hot flashes, night sweats, and associated insomnia.

Historically, postmenopausal hormone therapies containing estrogens were an effective treatment for vasomotor symptoms. Hormone therapy (HT) was generally regarded as one of the best pharmacological interventions for treating menopausal symptoms and preventing osteoporosis in postmenopausal women. However, the Women’s Health Initiative randomized trials found that the risks of HT, including breast cancer, stroke, venous thromboembolic events, cardiovascular disease and dementia, exceeded the benefits. These findings led the FDA to issue seven black box warnings for all estrogen-containing hormone therapies. These warnings have made physicians more reluctant to prescribe HT and women more disinclined to use HT, resulting in a dramatic drop in the number of women taking HT for treatment of menopausal symptoms. This represents an unmet medical need where safer alternative treatments to the currently available hormone therapies for menopausal symptoms are of utmost importance.

Menerba’s Mechanism of Action
Menerba is designed to treat vasomotor symptoms (hot flashes) associated with menopause. Representing a third generation of hormone receptor modulators, Menerba is an estrogen receptor beta agonist (ERBA). Unlike currently available non-selective estrogens contained in hormone therapies, Menerba does not activate the estrogen receptor alpha (ERα), known to be implicated in both breast and uterine cancer formation. Menerba is distinct from the FDA-approved selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, as these drugs have mixed agonist/antagonist activity and are NOT selective in transcriptional regulation to one of the two known estrogen receptor subtypes. Menerba has distinct chemical structural differences from steroidal estrogens in HT and SERMs resulting in receptor subtype selectivity, thereby, conferring different pharmacological and toxicity profiles.

Based on our studies conducted to date, there is clinical evidence that Menerba is effective for the treatment of vasomotor symptoms associated with menopause. Our studies also demonstrate that Menerba will not increase the risks for either breast or uterus cancer. Moreover, due to the absence of ERβ in hepatic cells, we believe Menerba will not result in an increased risk for venous thromboembolic events, a known side effect associated with the currently available HTs and SERMs.

Phase 1 Clinical Results
In a Phase 1 clinical trial of Menerba, conducted at the University of California, San Francisco, the drug was found to be safe, well tolerated and taken with high compliance. There was also statistically significant evidence of efficacy in the Phase 1 study.

Phase 2 Clinical Results
The Phase 2 clinical trial was designed to evaluate the safety and efficacy of 2 doses of Menerba versus placebo and was conducted under the direction of the esteemed women's health expert, Dr. Deborah Grady, at the University of California, San Francisco. The trial was a randomized, double-blinded, placebo-controlled study that enrolled 217 healthy postmenopausal women at 6 clinical sites in the U.S. who reported at least 50 moderate to severe hot flashes per week. Participants were randomized to receive Menerba 5 g/day, Menerba 10 g/day or identical placebo for 12 weeks.

The trial was completed by 98% of participants and 91% took at least 75% of assigned doses of study medication during the duration of the study. After 12 weeks of treatment, there was a statistically significant decrease in the frequency of all hot flashes in the higher dose of Menerba when compared to placebo. There was also a very clear dose response trend in multiple efficacy analyses, and statistical modeling indicated that higher doses of Menerba will lead to even greater reductions in the frequency of hot flashes. This trial provided evidence that treatment with Menerba reduced the frequency of hot flashes in healthy postmenopausal women and the drug was very well tolerated without any significant side effects.

The median reduction in the number of all hot flashes per week from baseline to 12 weeks of treatment was as follows: 68 to 41 in the placebo group, 63 to 32 in the Menerba low dose group and 67 to 31 in the Menerba high dose group. The difference in the median reduction in hot flashes per week after 12 weeks of treatment in the Menerba high dose group compared to placebo was statistically significant (p=0.04). Compared to placebo, women in the Menerba 10 g/day group were 2.3-fold more likely to have at least a 50% reduction in all hot flushes at 12 weeks of treatment (OR 2.3, p=0.03). Also of very important clinical significance, Menerba reduced the number of times women were woken up from sleep due to hot flashes, also known as “night awakenings” or “night sweats”. The median percent reduction in night time awakenings from hot flashes for women randomized to the higher dose of Menerba was 67%, and this reduction was statistically superior compared to placebo (p=0.05).

Menerba was very well tolerated and the only statistically significant side effect was loose stools (12% on Menerba versus 3% on placebo; p=0.03), which was most likely due to the presence of soluble fiber in Menerba. For future studies, manufacturing improvements have been implemented to reduce the fiber content in order to minimize this one side effect.

Safety analyses showed no cases of endometrial hyperplasia or uterine cancer during the trial and there were no differences in incidents of vaginal bleeding between the placebo group and the two cohorts treated with Menerba. Likewise, there was no increase in estradiol levels which further supports no untoward effect on either breast or uterine tissues that would lead to an increased risk for female cancers. There was no increase in blood pressure with treatment and there was a statistically significant decrease in both weight and body mass index (BMI) on the higher dose of Menerba compared to placebo.

 

FDA Approves Bionovo to Initiate Pivotal Trials for Menerba

Phase 1 Open Label Safety Study

Menerba Phase 3 Dose-Ranging Clinical Trial

Bionovo is now enrolling on a Phase 3 clinical trial evaluating the safety and efficacy of two doses of Menerba™ (MF101) among a cohort of postmenopausal women for the treatment of menopausal hot flashes. A total of 50 clinical sites in the U.S. will enroll 1,200 postmenopausal women between the ages of 40 and 65 years. Participants will be randomized to Menerba 5g/day, Menerba 10g/day or placebo and treated for 12 weeks. The primary aims of the study are to determine the safety and efficacy of two doses of Menerba compared to placebo after 12 weeks of treatment. Efficacy will be measured by the reduction of moderate to severe hot flushes from baseline to 12 weeks of treatment.

Menerba Phase 3 Clinical Trial Design

To learn more about Menerba and find a participating site, visit http://www.mf101.com

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

Wulf H. Utian is an independent consultant in women’s health issues, especially regarding new drug development, to the pharmaceutical and investment bank industries. He is considered to be one of the world’s most significant authorities on menopause and women’s health. Dr. Utian is the Executive Director Emeritus and Honorary Founding President of The North American Menopause Society (NAMS); the Arthur H. Bill Professor Emeritus of Reproductive Biology, Case Western Reserve School of Medicine; Consultant in Gynecology and Women’s Health, The Cleveland Clinic; Visiting Professor, University of Cape Town, South Africa (2007-2012); and Chairman of the Advisory Board of Rapid Medical Research, where he is an active research investigator. Previously, he was Director of Obstetrics and Gynecology at Mt. Sinai Medical Center of Cleveland, and then at University Hospitals of Cleveland and Chairman of Reproductive Biology at Case Western Reserve University.

Dr. Utian received his medical degree from the University of the Witwatersrand, Johannesburg, South Africa, and his PhD from the University of Cape Town, South Africa. In 2007 he earned the DSc (Med) degree from the University of Cape Town, it’s highest degree and awarded only 11 times in over 100 years. He is Board Certified in Obstetrics and Gynecology and Reproductive Endocrinology, and is a Fellow of the Royal College of Obstetricians and Gynaecologists, the American College of Obstetrics and Gynecology, and the International College of Surgeons. Dr. Utian is a credentialed NAMS Menopause Practitioner (NCMP), and is certified in Clinical Densitometry (CCD). He is the recipient of multiple research grants.

He has studied the metabolic and psychosocial aspects of hormones and menopause for over 40 years. During his career, Dr. Utian has written over 200 papers related to women’s health, and has authored five books on menopause. He is Honorary Founding Editor of Menopause, NAMS official scientific journal, and was Editor of Menopause Management, a NAMS-endorsed publication, from its inception in 1987 until December 2009. Dr. Utian has served on the NAMS Board of Trustees since he founded the Society in 1989. He is also one of the three original Founders in 1976 of the International Menopause Society, of which he is Honorary Past President, and serves on a number of national and international committees.

Dr. Utian has been a pioneer in women’s health issues and an innovator in several aspects of advanced reproductive technology. One of the early innovators of infertility microsurgery in the United States, he also developed one of the world’s first successful in vitro fertilization centers. He performed the world’s first surrogate in vitro fertilization procedure in 1984 in Cleveland. Numerous couples credit Dr. Utian with making it possible for them to have families.

A dedicated advocate for women’s health, Dr. Utian has achieved national and international recognition for his work and is interviewed regularly by the world’s leading media. He is the recipient of numerous national and international honors and awards. He has personally inspired many physicians and researchers to focus their work on menopause, not only improving the treatment of women around the age of menopause, but also expanding the research that informs such practice. His personal passion is the translation of research findings into best medical practices.