What is the effect of fezolinetant on patient-reported outcomes?

Published

Fezolinetant demonstrated improvements over placebo in Menopause-Specific Quality of Life (MENQoL) Total and Domain scores in both Phase 3 trials and in the real-world study.

  • Preliminary analyses from the ongoing, real-world Phase 4 OPTION-VMS observational study have provided complementary insights into the patient-reported impact of fezolinetant 45 mg on quality of life and symptom bother.1–3
  • Health-related quality of life (HRQoL) assessments were exploratory endpoints of the SKYLIGHT and DAYLIGHT studies during the double-blind periods.4,5 

Phase 4 real-world study, OPTION-VMS, preliminary results1,2 

  • In a preliminary analysis, within-group non-HT (non-hormone therapy) effects on VMS symptom bother evaluated using the VMS domain score of the patient reported outcome MENQOL (MENQOL VMS), overall and by subgroups of interest: 
    • Statistically significant within-group improvements from baseline in VMS bother were reported at Week 12 (primary outcome) and Weeks 4 and 8 (secondary outcomes) for women initially prescribed fezolinetant (n = 201), SSRIs/SNRIs (n = 329), and other non-HT (n = 126) (p < 0.001 for all).1–3,6  
    • Fezolinetant improvements from baseline were statistically significant at Weeks 4, 8, and 12 across subgroups (p ≤ 0.001 for all) with sufficient data, including: postmenopausal; moderate/severe baseline VMS; postmenopausal and moderate/severe baseline VMS; time since final menstrual period ≥ 2 to < 10 and ≥ 10 years; BMI ≥ 25 to < 30, ≤ 30 to < 35, and ≥ 35 kg/m2, age ≥ 50 to < 65 years, White and Black or African American race; and HT categories averse, naïve/willing, and unsuitable.2 Similar improvements were seen with SSRIs/SNRIs and other non-HTs, however, improvements were not statistically significant for the following subgroups for women initially prescribed other non-HT: time since final menstrual period ≥ 2 to < 10 years (Weeks 4, 8, and 12); BMI ≥ 25 to < 30 kg/m2 (Week 4).
  • Preliminary analysis of within-group non-HT effects on depressive and anxiety symptoms, measured by PHQ-9 (Patient Health Questionnaire-9) and GAD-7 (General Anxiety Disorder-7) patient-reported questionnaires:3
    • Fezolinetant improvements from baseline in PHQ-9 total scores were statistically significant (p < 0.001) at Weeks 4, 8, and 12. Significant improvements were also seen with SSRIs/SNRIs and other non-HT groups, but scores remained in the mild depression range through Week 12 in other non-HT group.
    • Fezolinetant showed statistically significant improvements (p < 0.001) from baseline in GAD-7 total scores at Weeks 4, 8, and 12. Similar improvements were seen with SSRIs/SNRIs and other non-HTs.

Pooled SKYLIGHT 1 and 2 data4 

The below analyses do not control the type I error rate, i.e. without multiplicity adjustment, so p-values do not confer statistical significance. Rather, the p-values were used for the purposes of hypothesis generation.

Figure 1: Change from Baseline to Weeks 4 and 12 in MENQoL Total Scorea4

All randomized participants assessed according to the randomization at first dose (fezolinetant 30 mg n = 339; fezolinetant 45 mg n = 341; placebo n = 342). Negative change indicates an improvement from baseline. aComprises all four domains and 29 items. Adapted from: Cano A, BJOG 2024.

Figure 2. Change from Baseline to Week 12 in MENQoL Domain Scores4

All randomized participants assessed according to the randomization at first dose (fezolinetant 30 mg n = 339; fezolinetant 45 mg n = 341; placebo n = 342). Negative change indicates an improvement from baseline. Adapted from: Cano A, BJOG 2024.

DAYLIGHT data5,7  

The analyses below do not control the type I error rate, i.e. without multiplicity adjustment, so p-values do not confer statistical significance. Rather, the p-values were used for the purposes of hypothesis generation.

Figure 4. Change from baseline to Week 24 in MENQoL Total Scorea5 

All randomized participants assessed according to the randomization at first dose (fezolinetant 45 mg n = 226; placebo n = 226). Negative change indicates an improvement from baseline. aComprises all four domains and 29 items. Adapted from: Shapiro M, Maturitas 2024.

Figure 5. Change from baseline to Week 24 in MENQoL Domain Scores5 

All randomized participants assessed according to the randomization at first dose (fezolinetant 45 mg n = 226; placebo n = 226). Negative change indicates an improvement from baseline. Adapted from: Shapiro M, Maturitas 2024.

  1. 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]. The Menopause Society (TMS) 2025 Annual Meeting. Orlando, FL, USA. 2025.

  2. Neal-Perry G, Mancuso S, Schild A, et al. Preliminary analysis of real-world effects of fezolinetant on menopause-specific quality-of-life vasomotor symptoms (MENQOL VMS) overall and by subgroups of interest: phase IV OPTION-VMS study [poster]. American College of Obstetricians & Gynecologists (ACOG) Annual Meeting. Washington, DC, USA. Poster #I23. 2026.

  3. Thurston RC, Mancuso S, Helbing M, et al. OPTIONVMS: Preliminary analysis of a phase 4 observational, realworld study of nonhormonal pharmacotherapies for bothersome menopauseassociated vasomotor symptoms and depression and anxiety [poster]. Endocrine Society Annual Meeting (ENDO) 2026. Chicago, IL, USA. 2026.

  4. Cano A, Nappi RE, Santoro N, et al. Fezolinetant impact on health‐related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials. BJOG: Int. J. Obstet. Gynaecol. 2024;131(9):1296-1305. Available at: https://doi.org/10.1111/1471-0528.17773.

  5. C.M. MS, Wu X, Wang X, et al. Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy. Maturitas. 2024;193108159. Available at: https://doi.org/10.1016/j.maturitas.2024.108159.

  6. 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]. The Menopause Society (TMS) 2025 Annual Meeting. Orlando, FL, USA. 2025.

  7. Schaudig K, Wang X, Bouchard C, et al. Efficacy and safety of fezolinetant for moderate-severe vasomotor symptoms associated with menopause in individuals unsuitable for hormone therapy: phase 3b randomised controlled trial. BMJ. 2024;387(387):e079525. Available at: https://doi.org/10.1136/bmj-2024-079525.

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