Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT

Abstract Context Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. Objective We aimed to assess efficacy/safety of fezolinetant for treatment of moderate to severe VMS associated with menopause. Methods In this double-blind, placebo-controlled, 12-week phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to week 4 (W4) and W12 in VMS frequency and severity. Safety was also assessed. Results Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, –1.82 (0.46; P < .001); 45 mg, –2.55 (0.46; P < .001); W12: 30 mg, –1.86 (0.55; P < .001); 45 mg, −2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, −0.15 (0.06; P < .05); 45 mg, −0.29 (0.06; P < .001); W12: 30 mg, −0.16 (0.08; P < .05); 45 mg, −0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively. Conclusion Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause.