Fezolinetant Treatment of Moderate-to-Severe Vasomotor Symptoms Associated With Menopause: Effect of Intrinsic and Extrinsic Factors in Two Phase 3 Studies [ID: 1356963

Abstract

INTRODUCTION: Fezolinetant was well tolerated and effective in reducing the frequency and severity of menopause-associated, moderate-to-severe vasomotor symptoms (VMSs) in SKYLIGHT 1 and 2. This analysis investigated the relationship between intrinsic (individual-related) and extrinsic (outside-influence) factors and fezolinetant efficacy. METHODS: In these phase 3, double-blind, placebo-controlled, IRB-approved studies (NCT04003155 and NCT04003142), women aged 40 through 65 years with moderate-to-severe VMSs (seven or more hot flushes/day) were randomized to once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. For this pooled analysis, the influence of intrinsic and extrinsic factors on change from baseline to week 12 in the frequency of moderate-to-severe VMSs was assessed by subgroups using a mixed model for repeated measurement. RESULTS: One thousand twenty-two women took one or more dose (placebo, n=342; fezolinetant 30 mg, n=339; fezolinetant 45 mg, n=341). Consistent improvements in VMS frequency over placebo were observed across subgroups with fezolinetant 45 mg. For intrinsic factors, least-square mean differences (95% CI) between fezolinetant 45 mg and placebo were as follows: age less than 55 years, −2.78 (−3.74, −1.82); 55 years or older, −2.24 (−3.23, −1.24); White race, −2.17 (−2.93, −1.41); Black race, −3.67 (−5.32, −2.01); and body mass index of 30 kg/m2 or higher, −2.87 (−4.11, −1.63). Extrinsic factors showed the following differences: current smoker, −3.48 (−5.19, −1.77); former/never smoker, −2.32 (−3.08, −1.57); European resident, −1.50 (−2.73, −0.26); and North American resident, −2.95 (−3.78, −2.13). Similar efficacy trends were observed with fezolinetant 30 mg. CONCLUSION: Fezolinetant was efficacious in treating moderate-to-severe VMSs associated with menopause across the intrinsic and extrinsic factors investigated, demonstrating its potential utility in a broad population.