New hot-flush treatment VEOZA▼™ (fezolinetant): first-in-class non-hormonal medicine for moderate to severe vasomotor symptoms associated with menopause licensed in Great Britain

- Non-hormonal mechanism reduces the number and intensity of hot-flush and night sweats in menopause   - Moderate to severe VMS in postmenopausal women in the UK has been reported at 40%.     Great Britain, December 18, 2023 – Astellas Pharma Ltd. today announced the Medicines and Healthcare products Regulatory Agency (MHRA) on December 18 licensed VEOZA™ (fezolinetant) 45 mg once daily for the treatment of moderate to severe vasomotor symptoms (VMS – also known as hot flushes and night sweats) associated with menopause.     Fezolinetant is the first of a new class of treatments, neurokinin-3 (NK3) receptor antagonists, to be licensed in Great Britain. The non-hormonal mechanism of action targets the neurological cause of VMS in the hypothalamus and represents a breakthrough in an area that has seen limited advances in many years.1     Dr Timir Patel, Medical Director, Astellas UK “The authorisation is testament to the scientific community who have been directly and indirectly involved in developing a targeted way of reducing VMS symptoms.”   VMS is triggered by an imbalance in the brain’s temperature control centre (the hypothalamus). Before menopause, there is a balance between oestrogens, a female sex hormone, and a protein made by the brain, neurokinin B (NKB), that regulates the brain’s temperature control centre.1 As the body goes through menopause, oestrogen levels decline and this balance is disrupted.1 Fezolinetant blocks neurokinin B binding in the temperature control centre, preventing the signal which can lead to VMS; reducing the number and intensity of hot flushes and night sweats.1   Marci English, Vice President, Head of BioPharma Development, Astellas “Fezolinetant’s novel mechanism of action targets the root cause of moderate to severe VMS associated with menopause.1 We are proud to have developed an innovative treatment option for a condition that has lacked scientific advancement for too long.”   Hot flushes and night-sweats are common symptoms of menopause and can have a disruptive impact on sleep, daily activities, and overall quality of life. 2, , ,   Moderate to severe VMS in postmenopausal women in the UK has been reported at 40%.2     Diane Danzebrink, Founder Director, Menopause Matters "Hot flushes and night sweats are common menopause symptoms which can be debilitating, affecting personal health and wellbeing, family lives and careers. It’s welcome news that doctors will have an alternative option to consider during a consultation, according to individual suitability. The decision is particularly important for those who’ve felt overlooked in the past in terms of treatment options, or those who prefer not to use HRT. “ The licence follows the submission of a European Commission Decision Reliance Procedure marketing authorisation application to the MHRA. This follows a positive opinion issued in October by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based on the results from the BRIGHT SKY™ program, which included three randomised Phase 3 clinical trials as part of a development program that collectively enrolled over 3,000 across Europe, the U.S. and Canada. Results from the SKYLIGHT 1™ and SKYLIGHT 2™ pivotal trials characterise the efficacy and safety of fezolinetant versus placebo for the treatment of moderate to severe VMS associated with menopause and were published in The Lancet and The Journal of Clinical Endocrinology & Metabolism, respectively. ,  Data from the SKYLIGHT 4™ safety study further characterises the long-term safety profile of fezolinetant and was published in Obstetrics & Gynecology.    About the BRIGHT SKY™ Phase 3 Program  The BRIGHT SKY pivotal trials, SKYLIGHT 1™ (NCT04003155) and SKYLIGHT 2™ (NCT04003142), enrolled over 1,022 women with moderate to severe VMS. The trials are randomised 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. The four co-primary efficacy endpoints for both studies were the change from baseline in moderate to severe VMS frequency and severity to weeks 4 and 12. Each study demonstrated a statistically significant and clinically meaningful (≥ 2 hot flashes per 24 hours) reduction from baseline in the frequency of moderate to severe VMS to weeks 4 and 12 for fezolinetant 45 mg compared to placebo.6,7    Pooled data from the SKYLIGHT 1 & 2 studies (n=683) showed a statistically significant 52.84% reduction [p-value<0.001] in the number of moderate to severe VMS episodes per day at week 4 and 62.80% reduction [p-value<0.001] at week 12.    • Baseline: number of moderate to severe VMS episodes per day: fezolinetant (n=341) mean 11.10 (SD:6.45) and placebo (n=342) mean 11.04 (SD:4.46) • Week 4: Change from baseline: fezolinetant -5.79 (52.84%, SE:0.23) vs. placebo -3.51 (31.96%, SE:0.22) • Week 12: Change from baseline: fezolinetant -6.94 (62.80%, SE:0.25) vs. placebo -4.43 (40.18%, SE:0.25)    The severity of VMS was recorded on a scale of 1 to 3*, with 3 being the most severe (sensation of heat with sweating, causing cessation of activity). At baseline, an average severity score of 2.40, between moderate and severe, was reported. By weeks 4 and 12 a statistically significant [p-value<0.001] reduction in the severity of VMS to 1.87 and 1.73 respectively, i.e. between mild to moderate, was observed compared to placebo.9     • Baseline: Severity of VMS symptoms: fezolinetant 2.40 mean (SD: 0.35) vs. placebo 2.42 mean (SD:0.34)  • Week 4: Change from baseline: fezolinetant -0.53 (SE: 0.03) vs. placebo -0.30 (SE:0.03) • Week 12: Change from baseline: -0.67 (SE: 0.04) vs. placebo -0.42 (SE: 0.04)   *Scale definitions - 1, mild: sensation of heat without sweating; 2, moderate: sensation of heat with sweating, able to continue activity; and 3, severe: sensation of heat with sweating, causing cessation of activity    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. The most common (≥1/100 to <1/10) adverse reactions with fezolinetant 45 mg were diarrhoea, insomnia, abdominal pain, alanine aminotransferase (ALT) increase and aspartate aminotransferase (AST) increase.8,9   About VEOZA™ (fezolinetant) VEOZA (fezolinetant) is a non-hormonal neurokinin 3 (NK3) receptor antagonist indicated in Great Britain, USA, EU and European Economic Area countries for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. VMS are also known as hot flushes or night sweats. VEOZA works by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron to modulate neuronal activity in the brain’s temperature control centre (the hypothalamus) to reduce the number and intensity of hot flushes and night sweats. ,     Important Safety Information The full Summary of Product Characteristics (SPC/SmPC) for fezolinetant in Great Britain will be available from the Electronic Medicines Compendium UK: www.medicines.org.uk  About Astellas 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.    Cautionary Notes 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.