A yearlong international phase 3 clinical trial has found that elinzanetant, a dual NK 1 and NK 3 receptor antagonist, can reduce hot flashes by nearly three quarters while maintaining a strong safety profile, positioning it as a promising non-hormonal treatment option for menopausal women. The findings, published in JAMA Internal Medicine, represent the first long term evaluation of the drug’s efficacy and safety over fifty-two weeks.
Elinzanetant acts on neural pathways believed to drive vasomotor symptoms, one of the most common and disruptive complaints of menopause. Declining estrogen levels during menopause disturb KNDy neuron activity, leading to elevated neurokinin B and substance P. By blocking NK 1 and NK 3 receptors, the drug aims to restore temperature regulation and reduce the frequency of hot flashes.
The OASIS 3 trial enrolled 628 postmenopausal women aged 40 to 65 years across 83 sites in North America and Europe. Participants were randomly assigned to receive either 120 milligrams of elinzanetant or placebo once daily for a full year. Symptoms were tracked through electronic diaries, and sleep and quality of life were assessed throughout the study period.
At the start of the trial, women experienced an average of 6.7 moderate to severe hot flashes per day. By week 12, which served as the primary assessment point, elinzanetant reduced daily vasomotor symptoms by an average of 5.4 episodes, compared with 3.5 in the placebo group. This represented a 73.8% reduction for the treatment group versus 47% for placebo. By week 50, women receiving elinzanetant averaged only 1.4 hot flashes per day, compared with 3.5 in the placebo arm.
Safety findings over the full year were encouraging. About 70% of participants receiving elinzanetant and 61% in the placebo group reported at least one treatment emergent adverse event, most of which were mild or moderate, including headache, nasopharyngitis, fatigue, and sleepiness. Discontinuation rates were low. No cases of endometrial hyperplasia, malignant changes, significant hormonal alterations, or concerning weight changes were reported. A small number of participants experienced increased liver enzyme levels, but no serious liver injury occurred.
The results build on earlier evidence from the OASIS 1 and OASIS 2 trials, which showed that elinzanetant significantly reduced both the frequency and severity of vasomotor symptoms and improved sleep and quality of life over twenty-six weeks.
Experts say the findings come at a time when the burden of menopausal symptoms is receiving greater attention globally, including in India, where hot flashes and night sweats affect an estimated 60 to 80% of women during the menopausal transition. Many women experience symptoms for five to ten years, yet access to hormone therapy remains limited by safety concerns, cultural hesitancy, and availability of trained providers. Non-hormonal treatment options are particularly sought after in India, where a large portion of women prefer therapies that avoid hormonal exposure and where unmet need for effective symptom relief remains high.
Researchers note that the new data strengthen the case for elinzanetant as a well-tolerated and effective non hormonal therapy at a time when alternatives to hormone therapy are in high demand. If approved, the drug could represent an important advance in long term menopausal care for millions of women worldwide.
Reference
- Panay N, Joffe H, Maki PM, Nappi RE, Pinkerton JV, Simon JA, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial. JAMA Intern Med. 2025 Nov 1;185(11):1319–27.
- Hager M, Goldstein T, Fitz V, Ott J. Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms. Expert Opin Pharmacother. 2024 May;25(7):783-789.
- Pinkerton JV, Simon JA, Joffe H, Maki PM, Nappi RE, Panay N, Soares CN, Thurston RC, Caetano C, Haberland C, Haseli Mashhadi N, Krahn U, Mellinger U, Parke S, Seitz C, Zuurman L. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. 2024 Aug 22;332(16):1343–54.