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 (2023). Efficacy and Safety of Fezolinetant in Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. The Journal of clinical endocrinology and metabolism, 108(8), pp. 1981-1997. The Endocrine Society 10.1210/clinem/dgad058

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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 (W) phase 3 trial with a 40W active treatment extension (NCT04003142; SKYLIGHT 2) women aged 40-65 years with minimum average 7 moderate-to-severe VMS/day were randomized to 12 weeks' 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 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; maintained through W52. Serious TEAEs were infrequent; these were reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.

CONCLUSIONS

Daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for treating moderate-to-severe VMS associated with menopause.

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