Elinzanetant Reduces Menopausal Vasomotor Symptoms in Phase 3 Trial

Key Takeaways

• Elinzanetant was associated with a larger week-12 reduction in daily moderate to severe vasomotor symptom frequency than placebo.
• Descriptive follow-up findings showed numerical advantages for symptom frequency and severity, sleep disturbance, and menopause-related quality of life.
• Treatment-related adverse events were more common with elinzanetant, but no hepatotoxic effect signal, endometrial hyperplasia, or meaningful bone changes were reported.

In the OASIS-3 trial of elinzanetant, once-daily oral elinzanetant 120 mg produced larger week-12 declines in moderate to severe vasomotor symptom frequency than placebo in postmenopausal women. Mean daily symptom frequency fell by 5.4 from baseline with elinzanetant and by 3.5 with placebo. The least-squares mean difference was -1.6, with a 95% CI of -2.0 to -1.1 and P<.001. The 52-week trial also provided longer-term tolerability and organ-specific safety data alongside the short-term efficacy result.

OASIS-3 was a double-blind, placebo-controlled, randomized phase 3 trial conducted at 83 sites in North America and Europe from August 27, 2021, to February 12, 2024. The study randomized 628 postmenopausal women aged 40 to 65 years, including naturally and surgically postmenopausal participants, to elinzanetant or matching placebo in a 1:1 ratio for 52 weeks. Women were seeking treatment for moderate to severe vasomotor symptoms, and enrollment did not require a minimum number of symptom events per week. Baseline mean age was 54.7 years. The prespecified primary endpoint was change to week 12 in daily moderate to severe symptom frequency, analyzed with a mixed model with repeated measures. The broader entry criteria and year-long placebo-controlled period widened the trial's scope beyond earlier phase 3 populations.

Secondary and exploratory endpoints were assessed descriptively, so the longer-term findings were presented as numerical differences rather than confirmatory comparisons. By week 50, mean daily moderate to severe vasomotor symptom frequency was 1.4 with elinzanetant and 3.5 with placebo. Numerical advantages for elinzanetant were also reported for symptom severity over 50 weeks and for PROMIS sleep disturbance and MENQOL total scores over 52 weeks. The investigators described OASIS-3 as expanding on findings from the 26-week OASIS-1 and OASIS-2 trials. It was also the first phase 3 evaluation of elinzanetant beyond 6 months in this population, with numerical separation maintained across symptoms and patient-reported outcomes.

Treatment-emergent adverse events occurred in 70.0% of the elinzanetant group and 61.1% of the placebo group, while study drug-related events occurred in 30.4% and 14.6%, respectively. Somnolence, fatigue, and headache were the most frequent treatment-related events, and most adverse events were mild or moderate. Discontinuations due to adverse events occurred in 12.5% and 4.1% of participants, and serious treatment-emergent adverse events occurred in 4.2% and 1.9%, with none considered treatment related. No hepatotoxic effect signal was identified, with no Hy law cases, cholestatic injury, or acute liver failure, and endometrial biopsy found no hyperplasia or malignant neoplasms. Bone density and bone turnover markers showed no meaningful changes, leaving a 52-week report with a higher adverse-event burden but no major liver, endometrial, or bone safety signal.