First Phase 3 trial evaluating the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause (OASIS 2) - IP05-C
Saturday, May 18, 2024
9:30 AM – 10:30 AM PDT
Location: Hall C
Authors:Rebecca Thurston PhD; Susanne Parke BS; Claudia Haberland PhD; Ulrike Krahn PhD; Christian Seitz MD
Professor of Obstetrics and Gynecology University of Virginia Health System University of Virginia CHARLOTTESVILLE - VA, Virginia, United States
Introduction: There is a need for effective non-hormonal treatments to alleviate menopausal vasomotor symptoms (VMS) and sleep disturbances. OASIS-2 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 120mg (n=200) or placebo (n=200) 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 menopause-related 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: -3.04 [SE: 0.69], p < 0.0001 [one-sided]; 12: -3.24 [0.69], p < 0.0001) and severity (week 4: -0.22 [0.06], p=0.0003; 12: -0.29 [0.08], 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=0.0013), and improved sleep disturbances (p < 0.0001) and menopause-related quality-of-life (p=0.0059) 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 disturbances, and menopause-related quality-of-life in postmenopausal women.