Objective: To assess efficacy and safety of fezolinetant in women unsuitable for hormone therapy (HT), using pooled SKYLIGHT 1 and 2 data.
Methods: 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.
Results: A total of 1,022 participants received ≥1 dose of study medication (fezolinetant 30 mg, = 339; fezolinetant 45 mg, = 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; < .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; = .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.
Conclusion: This pooled analysis demonstrated efficacy of fezolinetant vs. placebo in reducing frequency and severity of VMS due to menopause in participants unsuitable for HT.
Clinical Trial Registration: 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).
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