FDA Accepts Bayer's Elinzanetant for Review in Menopausal Vasomotor Symptoms
Key Insights
The FDA has accepted Bayer's New Drug Application (NDA) for elinzanetant, a dual neurokinin-1 (search),3 receptor antagonist, for treating moderate to severe vasomotor symptoms (search) (VMS) associated with menopause (search).
The NDA is supported by positive data from the Phase III OASIS 1, 2, and 3 trials, demonstrating significant reductions in VMS frequency and severity compared to placebo.
Elinzanetant, administered orally once daily, modulates KNDy neurons in the hypothalamus, addressing the root cause of VMS due to estrogen decline.
The U.S. Food and Drug Administration (FDA) has accepted Bayer's New Drug Application (NDA) for elinzanetant, an investigational compound aimed at treating moderate to severe vasomotor symptoms (search) (VMS) associated with menopause (search). This marks a significant step toward providing a novel, non-hormonal treatment option for millions of women experiencing these symptoms.
Elinzanetant is the first dual neurokinin-1 (search) and 3 (NK-1,3) receptor antagonist in late-stage clinical development for the non-hormonal treatment of moderate to severe VMS associated with menopause (search), administered orally once daily. It works by modulating KNDy neurons, a group of estrogen-sensitive neurons in the hypothalamus region of the brain. During menopause, declining estrogen levels cause these neurons to become hypertrophic, leading to hyperactivation of the thermoregulatory pathway and subsequent VMS.
The NDA submission is based on positive results from three Phase III studies: OASIS 1, OASIS 2, and OASIS 3. These trials evaluated the efficacy and safety of elinzanetant versus placebo in postmenopausal women aged 40 to 65 years with moderate to severe VMS.
OASIS 1 and 2 Trials
The OASIS 1 and 2 trials were double-blind, randomized, placebo-controlled studies. Participants were randomized 1:1 to receive elinzanetant 120mg orally once daily for 26 weeks or placebo once daily for 12 weeks, followed by elinzanetant 120mg for 14 weeks. The primary endpoints for both trials were the mean change in frequency and severity of moderate to severe VMS from baseline to week 4 and week 12.
All four primary endpoints were met:
- Elinzanetant reduced VMS frequency at week 4 (OASIS 1: -3.3 [95% CI, -4.5 to -2.1; P <.001]; OASIS 2: -3.0 [95% CI, -4.4 to -1.7; P <.001]).
- Elinzanetant reduced VMS frequency at week 12 (OASIS 1: -3.2 [95% CI, -4.8 to -1.6; P <.001]; OASIS 2: -3.2 (95% CI, -4.6 to -1.9; P <.001]).
- Elinzanetant improved VMS severity at week 4 (OASIS 1: -0.3 [95% CI, -0.4 to -0.2; P <.001]; OASIS 2: -0.2 (95% CI, -0.3 to -0.1; P <.001]).
- Elinzanetant improved VMS severity at week 12 (OASIS 1: -0.4 [95% CI, -0.5 to -0.3; P <.001]; OASIS 2: -0.3 (95% CI, -0.4 to -0.1; P <.001]).
Elinzanetant also improved sleep disturbances (search) and menopause (search)-related quality of life at week 12 with favorable safety data.
OASIS 3 Trial
The OASIS 3 trial was a double-blind, randomized, placebo-controlled study that investigated the long-term efficacy and safety of elinzanetant in postmenopausal women aged 40 to 65 years with moderate to severe VMS. Participants were randomly assigned to receive elinzanetant 120mg or placebo once daily for 52 weeks. The primary endpoint was the frequency of moderate to severe VMS from baseline to week 12.
Findings showed treatment with elinzanetant after 12 weeks statistically significantly reduced the frequency of moderate to severe VMS from baseline. The number of VMS episodes was reduced to 1.6 (SD 2.5) in the elinzanetant group and 3.4 (SD 4.2) in the placebo group.
Elinzanetant additionally improved sleep disturbances (search) and menopause (search)-related quality of life over 52 weeks with favorable safety data.
Expert Commentary
“The NDA acceptance of elinzanetant by the FDA marks a significant milestone in our efforts to advance menopause (search) care for women in the US,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization, Member of the Pharmaceutical Leadership Team at Bayer. “If approved, elinzanetant will offer a new non-hormonal option to women seeking treatment for moderate to severe vasomotor symptoms (search) and we look forward to the review by the agency.”
Additional Studies
The elinzanetant development program also includes the OASIS 4 trial, which is evaluating the efficacy and safety of elinzanetant in women with moderate to severe VMS caused by endocrine therapy used for breast cancer (search) treatment or prevention.
Additionally, an exploratory phase 2 study, NIRVANA, is underway to assess the effect of elinzanetant on sleep disturbances (search) associated with menopause (search) as determined by polysomnography.
Market Opportunity
By 2030, the global population of women experiencing menopause (search) is projected to increase to 1.2 billion, with 47 million women entering this phase each year. Vasomotor symptoms (search) are reported by up to 80% of women at some point during the menopausal transition and are one of the leading causes for women to seek medical attention. The availability of a safe and effective non-hormonal treatment option like elinzanetant could significantly improve the quality of life for many women.