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

Johnson, Kimball A.; Martin, Nancy; Nappi, Rossella E.; Neal-Perry, Genevieve; Shapiro, Marla; Stute, Petra; Thurston, Rebecca C.; Wolfman, Wendy; English, Marci; Franklin, Catherine; Lee, Misun; Santoro, Nanette

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.

VASOMOTOR system; MENOPAUSE

Journal of Clinical Endocrinology & Metabolism, 2023, Vol 108, Issue 8, p1981

0021-972X

Academic Journal

10.1210/clinem/dgad058