Bayer Submits NDA for Elinzanetant for the Treatment of Moderate to Severe Vasomotor Symptoms Associated With Menopause

Bayer recently announced that a New Drug Application (NDA) for the investigational compound elinzanetant has been submitted to the US FDA for the treatment of moderate to severe vasomotor symptoms (VMS, also known as hot flashes) associated with menopause. The submission is based on the positive results from the Phase 3 OASIS 1, 2 and 3 studies.

“Half of the world’s population will experience menopause, with 27 million women in the US currently experiencing this transition. 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 limitations of treatment options available,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization, Member of the Pharmaceutical Leadership Team at Bayer. “The FDA submission for elinzanetant marks a significant milestone in our efforts to offer a new non-hormonal option for women. This further underscores our position as leaders in Women’s Health and our dedication to addressing the unmet medical needs of women globally.”

The submission is based on positive results from the OASIS 1, 2 and 3 Phase 3 studies evaluating the efficacy and safety of the investigational compound elinzanetant versus placebo. Findings showed that elinzanetant (120 mg orally once daily) significantly reduced the frequency and severity of moderate-to-severe VMS and demonstrated a favorable safety profile with headache and fatigue being the most frequent treatment emergent adverse events (TEAEs) within the elinzanetant groups. 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.

The full results of OASIS 1 and 2 were recently presented at the 2024 American College of Obstetricians and Gynecologists (ACOG) Annual Clinical & Scientific Meeting. Positive topline results for the Phase 3 study OASIS 3 were announced in March 2024, providing additional supporting efficacy data as well as safety data of elinzanetant over 52 weeks, with details being presented at an upcoming scientific meeting.

Hot flashes are among the most frequently reported symptoms of menopause, a transitional phase in a woman’s life expected to affect 1.2 billion women worldwide by 2030. Hot flashes have also been shown to negatively impact women’s quality of life and are one of the leading causes for women to seek medical attention. It is important that additional options become available to give women a choice on how to address these symptoms.

Bayer will submit applications for marketing authorizations of elinzanetant for the treatment of moderate to severe VMS associated with menopause to other health authorities as well.

OASIS 1 and 2 are double-blind, randomized, placebo-controlled multicenter studies investigating the efficacy and safety of elinzanetant administered orally once daily in women with moderate to severe VMS associated with menopause over 26 weeks. OASIS 1 and 2 randomized 396 and 400 postmenopausal women between 40 and 65 years across 184 sites in 15 countries. OASIS 3 is a double-blind, randomized, placebocontrolled multicenter study to investigate the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms over 52 weeks in postmenopausal women. OASIS 3 – 3/6 – randomized 628 postmenopausal women between 40 and 65 years across 83 sites in 9 countries.

The Phase 3 clinical development program of elinzanetant, OASIS, currently comprises four Phase 3 studies: OASIS 1, 2, 3 and 4. The OASIS 1, 2 and 3 studies investigate the efficacy and safety of elinzanetant 120 mg in women with moderate to severe VMS associated with menopause. The OASIS 4 study is an expansion of the clinical Phase 3 program and investigates the efficacy and safety of elinzanetant in women with moderate to severe VMS caused by endocrine therapy for treatment or prevention of breast cancer.

The design and dosing of the Phase 3 clinical development program is based on the positive data from two Phase 2 studies (RELENT-1 and SWITCH-1). RELENT-1 was a Phase 1b/2a study investigating the safety, pharmacokinetics and preliminary efficacy of elinzanetant. SWITCH-1 was a Phase 2b study investigating the efficacy and safety of four different doses of elinzanetant compared to placebo in women with VMS.

In addition to the OASIS program, Bayer is conducting NIRVANA (NCT06112756), an exploratory Phase 2 randomized, parallel-group treatment, double-blind study. The primary objective is to explore the efficacy of elinzanetant on sleep disturbances associated with menopause as determined by polysomnography (PSG). PSG is a validated method to study sleep and underlying causes of sleep disturbances. Additional objectives include exploring the efficacy of elinzanetant on SDM as determined by patient-reported outcomes and further evaluating the safety of elinzanetant.

About Elinzanetant Elinzanetant is the first dual neurokinin-1 and 3 (NK-1 and 3) receptor antagonist, in late-stage clinical development for the non-hormonal treatment of moderate-to-severe VMS associated with menopause, administered orally once daily. Elinzanetant may address moderate-to-severe VMS by modulating a group of estrogen sensitive neurons in the hypothalamus region of the brain (the KNDy neurons) which, with the decrease of estrogen, become hypertrophic and lead to a hyperactivation of the thermoregulatory pathway, consequently disrupting body heat control mechanisms resulting in VMS. Elinzanetant may also decrease sleep disturbances associated with menopause.

Vasomotor symptoms (VMS; also referred to as hot flashes) result from hyperactivation of the thermoregulatory pathway mediated by hypertrophy of the KNDy neurons. This is due to a decrease of estrogen, which can result from the progressive reduction of ovarian function due to natural menopause or medical intervention by bilateral oophorectomy or endocrine therapy

Based on results from a large and diverse longitudinal study of menopausal transition in the US, 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. Over one-third of menopausal women report severe symptoms, which can last 10 years or more after the last menstrual period, 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. For these women, there are currently no approved treatment options.

By 2030, the global population of women experiencing menopause is projected to increase to 1.2 billion, with 47 million women entering this phase each year. Menopause is a transitional phase in women’s lives, related to the progressive decline of ovarian function. It usually occurs in women during their 40s or early 50s. It can also be the result of surgical or medical treatment such as breast cancer treatment. The hormonal decline can lead to various symptoms which can substantially affect a woman’s health, quality of life, healthcare utilization and work productivity. The most frequently reported and disruptive symptoms during the menopausal transition are VMS, sleep disturbances and mood changes. Addressing these symptoms is key to maintaining functional ability and quality of life in menopause which is highly relevant from both a healthcare and socioeconomic perspective.