Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials.

Key Points: Question: What are the efficacy and safety of elinzanetant, 120 mg, in postmenopausal individuals with moderate to severe vasomotor symptoms (VMS)? Findings: In 2 pivotal phase 3 clinical trials, elinzanetant demonstrated statistically significant reductions in VMS frequency and severity vs placebo. Elinzanetant also significantly improved sleep disturbances and menopause-related quality of life vs placebo; the safety profile was favorable. Meaning: Elinzanetant is an efficacious and well-tolerated selective neurokinin-1,3 receptor antagonist for the treatment of moderate to severe VMS associated with menopause. Elinzanetant also improves sleep disturbances and menopause-related quality of life. Importance: Safe and effective nonhormonal treatments for menopausal vasomotor symptoms (VMS) are needed. Objective: To evaluate the efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of moderate to severe menopausal vasomotor symptoms. Design, Setting, and Participants: Two randomized double-blind phase 3 trials (OASIS 1 and 2) included postmenopausal participants aged 40 to 65 years experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and Israel from August 27, 2021, to November 27, 2023, and OASIS 2: 77 sites in the US, Canada, and Europe from October 29, 2021, to October 10, 2023). Intervention: Once daily oral elinzanetant, 120 mg, for 26 weeks or matching placebo for 12 weeks followed by elinzanetant, 120 mg, for 14 weeks. Main Outcomes and Measures: Primary end points included mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary end points included Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total T score and Menopause-Specific Quality of Life questionnaire total score from baseline to week 12. Results: Eligible participants (mean [SD] age, OASIS 1: 54.6 [4.9] years; OASIS 2: 54.6 [4.8] years) were randomized to elinzanetant (OASIS 1: n = 199; OASIS 2: n = 200) or placebo (OASIS 1: n = 197; OASIS 2: n = 200). A total of 309 (78.0%) and 324 (81.0%) completed OASIS 1 and 2, respectively. For the elinzanetant and placebo groups, the baseline mean (SD) VMS per 24 hours were 13.4 (6.6) vs 14.3 (13.9) (OASIS 1) and 14.7 (11.1) v 16.2 (11.2) (OASIS 2). Baseline VMS severity was 2.6 (0.2) vs 2.5 (0.2) (OASIS 1) and 2.5 (0.2) vs 2.5 (0.2) (OASIS 2). Elinzanetant significantly reduced VMS frequency vs placebo 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) and 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 also improved VMS severity vs placebo 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) and 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 improved sleep disturbances and menopause-related quality of life at week 12, and the safety profile was favorable. Conclusions and Relevance: Elinzanetant was well tolerated and efficacious for moderate to severe menopausal VMS. Trial Registration: ClinicalTrials.gov Identifier: OASIS 1: NCT05042362, OASIS 2: NCT05099159 These 2 clinical trials evaluate the efficacy and safety of elinzanetant for the treatment of moderate to severe vasomotor symptoms associated with menopause. [ABSTRACT FROM AUTHOR]