Clinical Professor George Washington U and IntimMedicine Specialists George Washington University Washington, District of Columbia, United States
Introduction: Menopausal vasomotor symptoms (VMS) and sleep disturbances negatively impact women’s quality-of-life; however, an unmet need for effective therapies remains. OASIS-1 was a pivotal Phase 3 study evaluating the efficacy and safety of elinzanetant, a neurokinin-1,3 receptor antagonist, for the treatment of VMS. Methods: Postmenopausal women experiencing moderate/severe VMS were randomized 1:1 to elinzanetant 120 mg (n=199) or placebo (n=197) for 12 weeks (plus 14-week active-treatment extension). Primary endpoints for US were mean change from baseline in frequency and severity of moderate/severe VMS at weeks 4 and 12. Key secondary endpoints were mean change from baseline in: frequency of moderate/severe VMS at week 1; sleep disturbances (PROMIS SD-SF-8b total T-score) at week 12; and quality-of-life (MENQOL total score) at week 12. These endpoints were analyzed using mixed models with repeated measures. Safety was assessed through adverse events and laboratory/physical assessments. Results: Elinzanetant reduced VMS frequency and severity over 12 weeks. LS mean reductions were significant vs placebo for frequency (week 4: -3.29 [SE: 0.61], p < 0.0001 [one-sided]; 12: -3.22 [0.81], p < 0.0001) and severity (week 4: -0.33 [0.06], p < 0.0001; 12: -0.40 [0.07], p < 0.0001). Reductions in frequency were above the clinically relevant threshold of two VMS/day vs placebo. Compared with placebo, elinzanetant significantly reduced VMS frequency at week 1 (p < 0.0001), and improved sleep disturbances (p < 0.0001) and quality-of-life (p < 0.0001) at week 12. The safety profile was favorable. Headache and fatigue were more common with elinzanetant. Conclusion/Implications: Elinzanetant is well-tolerated and effectively improves VMS frequency and severity, sleep disturbance, and menopause-related quality-of-life in postmenopausal women.