Treating moderate to severe menopausal vasomotor symptoms with fezolinetant: responder analysis of the phase 3b DAYLIGHT study

Objectives: To characterize the efficacy of fezolinetant for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause using responder analyses of VMS frequency, patient-reported outcomes (PROs) of quality of life (QOL), and time to response. Methods: Prespecified analysis of DAYLIGHT (NCT05033886), a phase 3b, randomized, double-blind, 24-week, placebo-controlled study of fezolinetant in women considered unsuitable for hormone therapy. Two approaches for responder analyses: (1) participants with change from baseline in the frequency of moderate to severe VMS of ≥50%, ≥75%, and 100%, and (2) participants who experienced a clinically meaningful within-patient change (not placebo adjusted) compared with baseline in 1, 2, or 3 specified combinations of VMS frequency and PROs: the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total score, Menopause-Specific QOL total score, and Menopause-Specific QOL Vasomotor domain score. P values were nominal and not controlled for multiplicity. Results: Overall, 453 participants were randomized (placebo n = 226; fezolinetant 45 mg n = 227), and 370 (81.9%) of these completed the study (n = 175; n = 195, respectively). The full analysis set comprised 452 participants (placebo n = 226; fezolinetant 45 mg n = 226). Of these, 387 (85.6%) participants completed the 24-week treatment period. The proportion of participants with ≥50%, ≥75%, and 100% reductions in VMS frequency was higher in the fezolinetant 45 mg group than placebo throughout the treatment period. Week 24 odds ratio (OR) comparisons: ≥50% reduction: fezolinetant 45 mg: 60.6% versus placebo: 46.0%; OR: 1.82; 95% CI: 1.25 to 2.65; P = 0.002; ≥75% reduction: fezolinetant 45 mg: 46.9% versus placebo: 29.6%; OR: 2.10; 95% CI: 1.43 to 3.10; P < 0.001; 100% reduction: fezolinetant 45 mg: 22.1% versus placebo: 10.6%; OR: 2.39; 95% CI: 1.42 to 4.10; P = 0.001. Reductions in VMS frequency and severity were seen as early as week 1. A greater proportion of responders was observed in the fezolinetant 45 mg group versus placebo at week 24 in all responder analyses. ORs were supportive of a beneficial effect for fezolinetant 45 mg versus placebo (OR >1) for all PROs. Conclusions: Analyses of responders in the DAYLIGHT study showed higher, clinically meaningful responder rates and supported the treatment effect of fezolinetant relative to placebo in women unsuitable for hormone therapy.