European Medicines Agency Accepts Astellas' Marketing Authorization Application for Fezolinetant

If authorized by the European Commission, fezolinetant would be a nonhormonal treatment for moderate to severe vasomotor symptoms associated with menopause

TOKYO, Sept. 29, 2022 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced the European Medicines Agency (EMA) has accepted for regulatory review the company's marketing authorization application (MAA) for fezolinetant, an investigational oral, nonhormonal compound seeking approval for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. VMS, characterized by hot flashes and/or night sweats, are common symptoms of menopause.^1,2

"More than half of women 40 to 64 years of age experience hot flashes during menopause, with limited nonhormonal treatment options," said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. "The EMA's acceptance of our MAA for fezolinetant brings us one step closer to advancing a potential first-in-class nonhormonal treatment option for women in Europe who experience VMS associated with menopause, similar to the FDA acceptance of our NDA for women in the U.S."

The MAA is supported by results from the BRIGHT SKY™ program, which included three Phase 3 clinical trials that collectively enrolled over 2,800 women with VMS across Europe, the U.S. and Canada. Results from the SKYLIGHT 1™ and SKYLIGHT 2™ pivotal trials characterize the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS associated with menopause. Data from the SKYLIGHT 4™ safety study further characterizes the long-term safety profile of fezolinetant. Within the MAA, Astellas proposes a 45 mg daily dose, which is subject to the EMA's review.

Fezolinetant is an investigational nonhormonal selective neurokinin 3 (NK3) receptor antagonist. The safety and efficacy of fezolinetant are under investigation and have not been established.

This acceptance will have no impact on Astellas' financial forecasts of the current fiscal year ending March 31, 2023.

The BRIGHT SKY pivotal trials, SKYLIGHT 1™ (NCT04003155) and SKYLIGHT 2™ (NCT04003142), enrolled over 1,000 women with moderate to severe VMS. The trials are double-blinded, placebo-controlled for the first 12 weeks followed by a 40-week treatment extension period. Women were enrolled at over 180 sites within the U.S., Canada and Europe. SKYLIGHT 4™ (NCT04003389) is a 52-week double-blinded, placebo-controlled study designed to investigate the long-term safety of fezolinetant. For SKYLIGHT 4, over 1,800 women with VMS were enrolled at over 180 sites within the U.S., Canada and Europe.

VMS, characterized by hot flashes (also called hot flushes) and/or night sweats, are common symptoms of menopause.^1,2 Worldwide, more than half of women 40 to 64 years of age experience VMS with rates in Europe ranging from 56% to 97%.^3,4,5 The prevalence of moderate to severe VMS in postmenopausal women in Europe has been reported at 40%.⁶ VMS can have a disruptive impact on women's daily activities and overall quality of life.¹

Fezolinetant is an investigational oral, nonhormonal therapy in clinical development for the treatment of moderate to severe VMS associated with menopause. Fezolinetant works by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron to moderate neuronal activity in the thermoregulatory center of the brain (the hypothalamus) to reduce the frequency and severity of moderate to severe VMS associated with menopause.^7,8,9 The safety and efficacy of fezolinetant are under investigation and have not been established. There is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.

Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+^® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at https://www.astellas.com/en.

In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.

¹ Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47.

² Jones RE, Lopez KH, eds. Human Reproductive Biology. 4^th ed. Waltham, MA: Elsevier, 2014:120.

³ Makara-Studzinska MT, Krys-Noszczyk KM, Jakiel G. Epidemiology of the symptoms of menopause - an intercontinental review. Przegl Menopauzalny [Menopause Rev]. 2014;13:203-211.

⁴ Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health. 2006;96:1226-1235.

⁵ Williams RE, Kalilani L, DiBenedetti DB, et al. Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States. Climacteric. 2008;11:32-43.

⁶ Nappi RE, Kroll R, Siddiqui E, et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden. Menopause. 2021;28:875-882.

⁷ Depypere H, Timmerman D, Donders G, et al. Treatment of menopausal vasomotor symptoms with fezolinetant, a neurokinin 3 receptor antagonist: a phase 2a trial. J Clin Endocrinol Metab. 2019;104:5893-5905. 

⁸ Fraser GL, Lederman S, Waldbaum A, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020;27:382-392. 

⁹ Fraser GL, Hoveyda HR, Clarke IJ, et al. The NK3 receptor antagonist ESN364 interrupts pulsatile LH secretion and moderate levels of ovarian hormones throughout the menstrual cycle. Endocrinology. 2015;156:4214-4225. 

SOURCE Astellas Pharma Inc.