Is there an increase in VMS when fezolinetant is discontinued?

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Prescribing Information including BOXED WARNING

There are no suggestions from nonclinical or clinical data that rebound could be expected with fezolinetant treatment

In Phase 2 clinical trials, vasomotor symptoms (VMS) began returning within one week of treatment discontinuation.^1,2
In the Phase 3 trials SKYLIGHT 1, 2 and 4, ^3–5 dose increases and decreases were not allowed and the last dose of fezolinetant was administered without tapering.⁶ There was no evidence of a rebound effect on vasomotor symptoms (VMS) in the three-week follow-up periods.⁶
In VMS patients, the effective half-life of fezolinetant is predicted to be 9.6 hours.⁶

In SKYLIGHT 1 and 2, follow-up occurred approximately three weeks following the last dose of study drug (Week 55).⁶ Participants continued to record VMS frequency and severity through the follow-up visit (Figures 1 and 2).

Figure 1. Weekly mean frequency of moderate and severe VMS per 24 hours over the 52-week treatment period and follow-up period in SKYLIGHT 1 and 2^3,4,6

Adapted from: Johnson KA J Clin Endocr Metab. 2023 and Lederman S Lancet. 2023.

Figure 2. Weekly mean severity of moderate and severe VMS per 24 hours over the 52week treatment period and follow-up period in SKYLIGHT 1 and 2^3,4,6

Adapted from: Johnson KA J Clin Endocr Metab. 2023 and Lederman S Lancet. 2023.

Fraser GL, Lederman S, Waldbaum A, et al. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020;27(4):382-392. Available at: https://doi.org/10.1097/GME.0000000000001510.
Depypere H, Timmerman D, Donders G, et al. Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial. J Clin Endocr Metab. 2019;104(12):5893-5905. Available at: https://doi.org/10.1210/jc.2019-00677.
Johnson KA, Martin N, Nappi RE, et al. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT. J Clin Endocr Metab. 2023;108(8):1981-1997. Available at: https://doi.org/10.1210/clinem/dgad058.
Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401(10382):1091-1102. Available at: https://doi.org/10.1016/s0140-6736(23)00085-5.
Neal-Perry G, Cano A, Lederman S, et al. Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause: A Randomized Controlled Trial. Obstet Gynecol. 2023;141(4):737-747. Available at: https://doi.org/10.1097/aog.0000000000005114.
Data on file.