Can fezolinetant be used in patients older than 65 years?

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Prescribing Information including BOXED WARNING

The use of fezolinetant in women over 65 years of age is not contraindicated, although its use has not yet been studied in this age group.

In the Phase 3 SKYLIGHT trials, fezolinetant 45 mg significantly reduced vasomotor symptom (VMS) frequency regardless of age in patients 40 to 65 years old.¹ Baseline age (< 55 years and ≥ 55 years) did not have an impact on the incidence and type of treatment-emergent adverse events reported, nor on the risk of hepatic safety²
An ongoing real-world Phase 4 study, OPTION-VMS, assessing the change of vasomotor symptom bother in women initiating nonhormonal therapy, including fezolinetant, includes patients aged between 40 and 75 years^3,4

In a pooled efficacy analysis of the Phase 3 SKYLIGHT 1 and 2 trials, 1022 women aged ≥ 40 to ≤ 65 years were separated into subgroups of < 50 years, ≥ 50 to ≤ 60 years, and > 60 years old.¹ Compared with placebo at Week 12, fezolinetant 45 mg significantly reduced VMS frequency in all age groups (p < 0.05; Figure 1), and significantly reduced VMS severity (p < 0.05), except in the < 50 years subgroup (Figure 2).

Figure 1. Change in VMS frequency from baseline to Week 12 by baseline age in the full analysis set (all randomized participants assessed according to the randomization at first dose).¹

The number of participants with baseline data are shown.

P values were calculated without multiplicity adjustment.

Total number of participants – Fezolinetant 30 mg: n = 339, Fezolinetant 45 mg: n = 341, Placebo: n = 342.

Adapted from: Santoro NF, Menopause, 2024.

Figure 2. Change in VMS severity from baseline to Week 12 by baseline age in the full analysis set (all randomized participants assessed according to the randomization at first dose).¹

The number of participants with baseline data are shown.

P values were calculated without multiplicity adjustment.

Baseline results include moderate and severe incidences while post-baseline results include mild, moderate, and severe incidences.

Total number of participants – Fezolinetant 30 mg: n = 339, Fezolinetant 45 mg: n = 341, Placebo: n = 342.

Adapted from: Santoro NF, Menopause, 2024.

OPTION-VMS is an ongoing, Phase 4, longitudinal, multicenter, observational study of women prescribed non-hormonal therapy for VMS. Two preliminary analyses of the OPTION-VMS study were presented during The Menopause Society 2025 in Orlando, Florida.
In one of the preliminary analyses focused on assessing changes from baseline to week 12, it was reported that fezolinetant showed statistically significant improvements in MENQOL domains (VMS, sexual, psychosocial, and physical), PROMIS SD SF 8b total scores, and actigraphy endpoints, sleep onset (WASO), sleep efficiency, and sleep latency at week 12.³ The incidence of fezolinetant-related TEAEs was low, and no new safety signals were identified.
The other was a preliminary analysis of non-HT effect on work productivity measured with the 6-item patient-reported outcome, WPAI-VMS.⁴ It was reported that fezolinetant showed statistically significant within-group improvements (p < 0.001) from baseline in WPAI-VMS domains (overall work productivity loss, activity impairment, and presenteeism) at weeks 4, 8 and 12. Statistically significant within-group improvements from baseline were also seen for SSRIs/SNRIs (p < 0.001) and other non-HT treatments (p < 0.05).

Santoro N, Nappi RE, Neal-Perry G, et al. Fezolinetant treatment of moderate-to-severe vasomotor symptoms due to menopause: effect of intrinsic and extrinsic factors in two phase 3 studies (SKYLIGHT 1 and 2). Menopause. 2024;31(4):247-257. Available at: https://doi.org/10.1097/gme.0000000000002340.
Neal-Perry G, Cano A, Lederman S, et al. Safety of Fezolinetant for Vasomotor Symptoms Associated With Menopause. Obstet. Gynecol. 2023;141(4):737-747. Available at: https://doi.org/10.1097/aog.0000000000005114.
Neal-Perry G, Lederman S, Mancuso S, et al. OPTION-VMS: Preliminary Analysis of a Phase IV Observational, Real-World Study of Non-hormonal Pharmacotherapies for Bothersome Menopause-Associated Vasomotor Symptoms [poster]. Orlando, FL, USA. The Menopause Society (TMS) 2025 Annual Meeting; 2025.
Maki PM, Mancuso S, Helbing M, et al. Preliminary Analysis of Work Productivity Outcomes in OPTION-VMS: A Phase IV Observational, Real-World Study of Non-hormonal Treatment for Bothersome Menopause-Associated Vasomotor Symptoms [poster]. Orlando, FL, USA. The Menopause Society (TMS) 2025 Annual Meeting; 2025.