Summary: In 628 postmenopausal women seeking treatment for moderate-to-severe vasomotor symptoms, elinzanetant reduced daily symptom frequency more than placebo at week 12: adjusted difference -1.6 episodes per day (95% CI -2.0 to -1.1). Longer-term symptom and sleep findings were descriptive, and treatment-related adverse events were more common with active treatment.
PICO Summary
| Element | Detail |
|---|---|
| Population | 628 postmenopausal women aged 40-65 years at 83 sites in North America and Europe; no minimum weekly symptom-event count was required. Elinzanetant n=313; placebo n=315. |
| Intervention | Oral elinzanetant 120 mg once daily for 52 weeks; n=313. |
| Comparator | Matching placebo once daily for 52 weeks; n=315. |
| Outcomes | Primary week-12 change in daily moderate-to-severe vasomotor symptom frequency: -5.4 episodes with elinzanetant (95% CI -6.3 to -4.5) versus -3.5 with placebo (-4.1 to -2.9). The model-based least-squares difference was -1.6 episodes/day (95% CI -2.0 to -1.1; P<0.001), not the simple subtraction of displayed group means. Later sleep, quality-of-life and symptom outcomes were descriptive, without prespecified statistical hypotheses. In the safety population (313 active; 314 placebo), treatment-related adverse events occurred in 30.4% versus 14.6%, commonly somnolence, fatigue and headache. Adverse-event discontinuations: 12.5% versus 4.1%. Serious adverse events: 4.2% versus 1.9%, none considered treatment related. No hepatotoxicity or endometrial hyperplasia signal was identified, but rare harm is not excluded. |
| Study Design | OASIS-3: phase 3, randomised, double-blind, placebo-controlled, 52-week trial. Primary efficacy assessment at week 12 using a mixed model; secondary and exploratory outcomes analysed descriptively. Bayer funded and participated in design, conduct, analysis and reporting; several authors were company employees. ClinicalTrials.gov NCT05030584. |
Expert Commentary
I regard OASIS-3 as a positive trial for its prespecified week-twelve symptom endpoint, with useful but less definitive information about longer treatment. The adjusted difference was about one and a half fewer moderate-to-severe episodes daily beyond placebo, which should be discussed in relation to each patient's baseline burden and priorities. The important limitation is the distinction between confirmatory and descriptive evidence. Longer-term symptom, sleep and quality-of-life findings were not supported by prespecified statistical hypotheses, so they should not be given the same evidential weight as the primary result. Treatment-related adverse events were also substantially more common with elinzanetant, particularly somnolence, fatigue and headache. Reassuring liver, endometrial and bone observations during this study do not exclude uncommon or delayed harm. Can I use this with my patients? The findings can support discussion of a non-hormonal option for appropriately selected postmenopausal women, subject to local authorisation, contraindications and current prescribing information. They do not establish superiority to menopausal hormone therapy or to other active non-hormonal treatments. I would avoid promising sustained sleep benefit on the basis of descriptive analyses alone. The next priority should be longer safety surveillance and active-comparator studies that measure patient-important relief, daily functioning and treatment persistence in routine practice.
References
Panay N, Joffe H, Maki PM, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: A Phase 3 Randomized Clinical Trial. JAMA Intern Med. 2025;185(11):1319-1327. doi:10.1001/jamainternmed.2025.4421. PMID: 40920404.
