Fezolinetant effect on vasomotor symptoms due to menopause in women unsuitable for hormone therapy

To assess efficacy and safety of fezolinetant in women unsuitable for hormone therapy (HT), using pooled SKYLIGHT 1 and 2 data. SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies of once-daily placebo, fezolinetant 30 mg or 45 mg for 12 weeks in women aged ≥40–≤65 years with moderate to severe vasomotor symptoms (VMS; average ≥7 hot flashes/d), followed by a double-blind, non-controlled extension period for 40 weeks. The HT unsuitable group comprised 4 mutually exclusive subgroups, categorized using the following hierarchy: contraindicated; caution; stopper for medical concerns; averse. A total of 1,022 participants received ≥1 dose of study medication (fezolinetant 30 mg, <i>n</i> = 339; fezolinetant 45 mg, <i>n</i> = 341). Improvement was seen for the HT unsuitable group in frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 (mean difference [95% CI] fezolinetant 45 mg vs. placebo: −2.55; 95% CI, −3.29 to −1.80; <i>p</i> &lt; .001 at week 12). Sleep disturbance, measured by Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS-SD SF 8b) total score, improved by weeks 4 and 12 (mean difference [95% CI] fezolinetant 45 mg vs. placebo at week 12: −1.60; 95% CI, −2.71 to −0.49; <i>p</i> = .005). Fezolinetant was well tolerated in the HT unsuitable group, with treatment-emergent adverse events in 39.4% of participants receiving fezolinetant 45 mg vs. 41.3% receiving placebo. This pooled analysis demonstrated efficacy of fezolinetant vs. placebo in reducing frequency and severity of VMS due to menopause in participants unsuitable for HT. SKYLIGHT 1 – ClinicalTrials.gov, NCT04003155; https://clinicaltrials.gov/ct2/show/NCT04003155 (conducted between July 2019 and August 2021); SKYLIGHT 2 – ClinicalTrials.gov, NCT04003142; https://clinicaltrials.gov/ct2/show/NCT04003142 (conducted between July 2019 and April 2021).