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Clinical Trial
. 2023 Jul 14;108(8):1981-1997.
doi: 10.1210/clinem/dgad058.

Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT

Kimball A Johnson  1 , Nancy Martin  2 , Rossella E Nappi  3 , Genevieve Neal-Perry  4 , Marla Shapiro  5 , Petra Stute  6 , Rebecca C Thurston  7 , Wendy Wolfman  8 , Marci English  9 , Catherine Franklin  2 , Misun Lee  10 , Nanette Santoro  11
Affiliations
Clinical Trial

Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT

Kimball A Johnson et al. J Clin Endocrinol Metab. .

Abstract

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 phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of 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 week 4 (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 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.

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

Keywords: KNDy; fezolinetant; neurokinin 3 receptor antagonist; nonhormonal; vasomotor symptoms.

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Figures

Figure 1.
Figure 1.
Study flow chart. aVasomotor symptoms data collected using an electronic VMS diary. Minimum average of 7 moderate to severe VMS/day for 10 days before randomization.
Figure 2.
Figure 2.
Flow diagram.
Figure 3.
Figure 3.
Mean (A) frequency and (B) severity of moderate and severe VMS during the 52-week treatment period (FAS and FAS-fezolinetant exposure). Abbreviations: FAS, full analysis set; VMS, vasomotor symptoms.
Figure 4.
Figure 4.
(A) Distribution of the Patient Global Impression of Change in Sleep Disturbance at week 12 and (B) the Patient Global Impression of Severity in Sleep Disturbance at week 12 (full analysis set). Abbreviation: NA, not applicable.
Figure 5.
Figure 5.
Percentage reduction in frequency of moderate and severe VMS per 24 hours by week (FAS). Abbreviations: FAS, full analysis set; VMS, vasomotor symptoms.
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