Reading, UK, 17th September 2024 – Bayer has submitted a Marketing Authorisation Application (MAA) to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the investigational compound elinzanetant for the treatment of moderate to severe vasomotor symptoms (VMS, also known as hot flushes) associated with menopause in women. The submission is based on the positive results from the Phase III OASIS 1, 2 and 3 studies.
"Menopause is a significant transition in a woman's life, affecting around 13 million women in the UK who are currently going through perimenopause or menopause, which accounts for almost a third of the female population.1 Despite the impact menopausal symptoms may have on women’s health and quality of life, many go without treatment due to gaps in awareness, education, and limited treatment options," said Dr Joep Hufman, Country Medical Director, Bayer UK & Ireland. "The submission of elinzanetant to the MHRA represents a pivotal step in our efforts to offer a potential, alternative, non-hormonal treatment option for women, reinforcing our long-standing commitment to Women's Health in the UK."
The submission is based on positive results from the OASIS 1, 2 and 3 Phase III studies evaluating the efficacy and safety profile of the investigational compound elinzanetant (120mg orally once daily) in women with moderate to severe VMS associated with menopause versus placebo. Findings showed that elinzanetant significantly reduced the severity and frequency of moderate-to-severe VMS compared to placebo with headache and fatigue being the most frequently reported treatment emergent adverse events (TEAEs) within the elinzanetant groups in OASIS 1 and 2. Consistent improvements were also seen across OASIS 1 and 2 in all three key secondary endpoints, with significant reduction in frequency of VMS at week 1, improvement in sleep disturbances and menopause-related quality of life compared to placebo.
The full results of OASIS 1 and 2 were presented at the 2024 American College of Obstetricians and Gynaecologists (ACOG) Annual Clinical & Scientific Meeting in May and published in The Journal of the American Medical Association (JAMA)3 in August 2024. Positive results for the Phase III study OASIS 3 were presented last week at the 2024 Annual Meeting of The Menopause Society (TMS) as late-breaking data, confirming additional supporting efficacy data as well as safety data of elinzanetant over 52 weeks.
VMS, hot flushes, are among the most frequently reported symptoms of menopause, reported by up to 80% of women at some point during the menopausal transition.2 Hot flushes have also been shown to negatively impact women’s quality of life and are one of the leading causes for seeking medical attention during this phase of a woman’s life.2 Over one-third of menopausal women report severe symptoms, which can last 10 years or more after the last menstrual period.4,5
ENDS
Bayer media contact:
Veronica Yao, +44 (0) 7870 485 926
Email: veronica.yao@bayer.com
Notes to Editors
About the OASIS 1, 2 and 3 studies
OASIS 1 and 2 (NCT05042362 and NCT05099159) are double-blind, randomised, placebo-controlled multicentre studies investigating the efficacy and safety profile of elinzanetant 120mg administered orally once daily in women with moderate to severe VMS associated with menopause.6,7 OASIS 1 and 2 randomised 396 and 400 postmenopausal women between 40 and 65 years across 184 sites in 15 countries.6,7 The co-primary endpoints in the studies were mean change in frequency and severity of moderate to severe hot flush from baseline to Week 4 and 12.6,7 Results from the OASIS 1 and 2 were recently published in the Journal of the American Medical Association (JAMA).3
OASIS 3 (NCT05030584) is the third Phase III, double-blind, randomised, placebo-controlled multicentre study to investigate the efficacy and safety profile of elinzanetant for the treatment of VMS over 52 weeks in postmenopausal women.8 OASIS 3 randomised 628 postmenopausal women between 40 and 65 years across 83 sites in 9 countries.8 Results from OASIS 3 were presented at the 2024 Annual Meeting of The Menopause Society (TMS) as late-breaking data in September 2024. The data shows that elinzanetant successfully met the primary endpoint demonstrating a statistically significant mean reduction in the frequency of moderate to severe vasomotor symptoms from baseline to week 12 compared to placebo. Improvements in the elinzanetant arm were also seen in key secondary endpoints with a mean change from baseline in sleep disturbances and menopause related quality of life as shown by the total score over time. The safety profile of elinzanetant over 52 weeks was consistent with findings from the 26-week OASIS 1 and OASIS 2 studies.
About the OASIS Clinical Development Programme
The Phase III clinical development programme of elinzanetant, OASIS, currently comprises four Phase III studies: OASIS 1, 2, 3 and 4. The OASIS 1, 2 and 3 studies investigate the efficacy and safety profile of elinzanetant 120 mg once daily in women with moderate to severe VMS associated with menopause.6-9 The OASIS 4 study is an expansion of the clinical phase III programme and investigates the efficacy and safety profile of elinzanetant in women with moderate to severe VMS caused by endocrine therapy for treatment or prevention of breast cancer.9
The design and dosing of the Phase III clinical development programme is based on the positive data from two Phase II studies (RELENT-1 and SWITCH-1).10,11 RELENT-1 was a Phase Ib/IIa study investigating the safety, pharmacokinetics and preliminary efficacy of elinzanetant.10 SWITCH-1 was a Phase IIb study investigating the efficacy and safety of four different doses of elinzanetant compared to placebo in postmenopausal women with associated moderate to severe VMS.11
In addition to the OASIS programme, Bayer started NIRVANA (NCT06112756), an exploratory Phase II randomised, parallel-group treatment, double-blind study.12 The primary objective is to explore the efficacy of elinzanetant on sleep disturbances associated with menopause in women as determined by polysomnography (PSG).12 PSG is a validated method to study sleep and underlying causes of sleep disturbances.13 Additional objectives include exploring the efficacy of elinzanetant on SDM (sleep disturbances associated with menopause) as determined by patient-reported outcomes and further evaluating the safety profile of elinzanetant.12
About Elinzanetant
Elinzanetant is a dual neurokinin-1,3 (NK-1,3) receptor antagonist, in late-stage clinical development as a non-hormonal treatment of moderate to severe VMS associated with menopause in women, 120 mg administered orally once daily.11 Elinzanetant may address moderate to severe VMS by modulating a group of oestrogen sensitive neurons in the hypothalamus region of the brain (the KNDy neurons) which, with the decrease of oestrogen, become hypertrophic and lead to a hyperactivation of the thermoregulatory pathway, consequently disrupting body heat control mechanisms resulting in VMS.11 Elinzanetant is also being investigated in women with sleep disturbances associated with menopause.12
Elinzanetant is not licensed for use by regulatory authorities in any country.
About Vasomotor Symptoms
Vasomotor symptoms (VMS; also referred to as hot flushes) result from hyperactivation of the thermoregulatory pathway mediated by hypertrophy of the KNDy neurons.2 This is due to a decrease of oestrogen, which can result from the progressive reduction of ovarian function due to natural menopause or medical intervention by bilateral oophorectomy or endocrine therapy.2
VMS are reported by up to 80% of women at some point during the menopausal transition and are one of the leading causes for seeking medical attention during this phase of a woman’s life.2 Over one-third of menopausal women report severe symptoms, which can last 10 years or more after the last menstrual period,4,5 with relevant impact on quality of life.
VMS may also be caused by endocrine therapy, for the treatment or prevention of breast cancer, impacting quality of life and treatment adherence.14 For these women with VMS due to induced menopause, there are currently no licensed treatment options.
About Menopause
By 2030, the world population of women experiencing menopause is projected to increase to 1.2 billion, with 47 million new women entering this phase each year.15 Menopause is a transitional phase in women’s lives, related to the progressive decline of ovarian function, and which usually occurs in women between the ages of 45 and 55.16 It can also be the result of surgical or medical treatment, for example breast cancer treatment.9 The hormonal decline can lead to various symptoms, which can substantially affect a woman’s health, quality of life, healthcare utilisation and work productivity.17 The most frequently reported and disruptive symptoms during the menopausal transition include VMS and sleep disturbances.17 Addressing these symptoms is key to maintaining functional ability and quality of life in menopause, which is highly relevant from both a healthcare and socio-economic perspective.
About Women’s Healthcare at Bayer
Bayer is a recognised global leader in women’s health with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. Bayer offers a wide range of effective short- and long-acting birth control methods as well as therapies for menopause management and gynecological diseases. Bayer is also focusing on innovative options to address the unmet medical needs of women worldwide and to broadening treatment choices such as in menopause. Additionally, Bayer intends to provide 100 million women per year in low-and-middle income countries by 2030 with access to family planning by funding multi-stakeholder aid programs for capacity building and by ensuring the supply of affordable modern contraceptives. This is part of the comprehensive sustainability measures and commitments from 2020 onwards and in line with the Sustainable Development Goals of the United Nations.
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.co.uk.
Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.co.uk. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References
1. Wellbeing of Women. New data reveals big gap in access to hormone replacement therapy for ethnic minority and deprived women. Available at: https://www.wellbeingofwomen.org.uk/news/new-data-reveals-big-gap-in-access-to-hormone-replacement-therapy-for-ethnic-minority-and-deprived-women/#:~:text=The%20number%20of%20women%20aged,of%20the%20entire%20female%20population. Last accessed: September 2024.
2. Mittelman-Smith et al. Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. PNAS. November 27, 2012, vol. 109 no. 48|19849PHYSIOLOGY. www.pnas.org/cgi/doi/10.1073/pnas.1211517109.
3. Pinkerton J V et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause - OASIS 1 and 2 Randomized Clinical Trials. Journal of the American Medical Association (JAMA). August 2024. Available at: https://jamanetwork.com/journals/jama/fullarticle/2822766.
4. Angelo SD, et al. Impact of Menopausal Symptoms on Work: Findings from Women in the Health and Employment after Fifty (HEAF) Study. Int. J. Environ. Res. Public Health 2023, 20, 295. https://doi.org/10.3390/ijerph20010295.
5. Nancy E. Avis, et al. Vasomotor Symptoms Across the Menopause Transition: Differences Among Women. Obstet Gynecol Clin North Am. 2018 December ; 45(4): 629–640. doi:10.1016/j.ogc.2018.07.005.
6. A study to learn more about how well elinzanetant works and how safe it is for the treatment of vasomotor symptoms (hot flashes) that are caused by hormonal changes over 26 weeks in women who have through the menopause (OASIS-1). ClinicalTrials.gov. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05042362?term=OASIS&cond=Menopause&draw=1&rank=1. Last accessed: September 2024.
7. A study to learn more about how well elinzanetant works and how safe it is for the treatment of vasomotor symptoms (hot flashes) that are caused by hormonal changes over 26 weeks in women who have through the menopause (OASIS-2). ClinicalTrials.gov. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05099159?term=OASIS&cond=Menopause&draw=1&rank=3. Last accessed: September 2024.
8. A study to learn more about how well elinzanetant works and how safe it is for the treatment of vasomotor symptoms (hot flashes) that are caused by hormonal changes over 52 weeks in women who have through the menopause (OASIS-3). ClinicalTrials.gov. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05030584?term=OASIS&cond=Menopause&draw=1&rank=2. Last accessed: September 2024.
9. A study to learn more about how well elinzanetant works and how safe it is compared to placebo for the treatment of hot flashes caused by anti-cancer therapy in women with, or at high risk for developing hormone-receptor positive breast cancer (OASIS 4). EU Clinical Trials Register. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2022-000095-18/DE. Last accessed: September 2024.
10. Trower M, et al. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause: The Journal of The North American Menopause Society. 2020; 27 (5): 498-505.
11. Simon JA, Anderson RA, Ballantyne E, Bolognese J, Caetano C, Joffe H, Kerr M, Panay N, Seitz C, Seymore S, Trower M, Zuurman L, Pawsey S. Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause. 2023 Mar 1;30(3):239-246.
12. A Study to Learn About How Elinzanetant Works and How Safe it is in Women Having Sleep Disturbances Associated With Menopause (NIRVANA). ClinicalTrials.gov. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT06112756. Last accessed: March 2024.
13. Jessica Vensel Rundo, Ralph Downey III. Chapter 25 – Polysomnography. Handbook of Clinical Neurology. Volume 160, 2019, Pages 381-392.
14. Gucciniello L, et al. Estrogen deprivation effects of endocrine therapy in breast cancer patients: Incidence, management and outcome. Cancer Treatment Reviews 120 (2023) 102624. https://doi.org/10.1016/j.ctrv.2023.102624.
15. Kenneth Hill. The demography of menopause. Maturitas 23 (1996) 113-127. Journal of the Climacteric & Postmenopause. SSDI 0327-5122(95)00968-R.
16. Menopause. World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/menopause. Last accessed: March 2024.
17. Wulf H Utian. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: A comprehensive review. Health and Quality of Life Outcomes 2005, 3:47 doi:10.1186/1477-7525-3-47