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

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Prescribing Information including BOXED WARNING

In the Phase 3 trials SKYLIGHT 1 and 2 (pooled data) and DAYLIGHT, fezolinetant demonstrated improvements over placebo in Menopause-Specific Quality of Life (MENQoL) Total and Domain scores, and Patient Global Impression of Change in vasomotor symptoms (PGI-C VMS)

Health-related quality of life (HRQoL) assessments were exploratory endpoints of the SKYLIGHT and DAYLIGHT studies during the double-blind periods.^1,2
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.^3–5

Pooled SKYLIGHT 1 and 2 data¹

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 Score^a¹

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 Scores¹

PGI-C VMS¹

Improvements in PGI-C VMS were larger for fezolinetant 45 mg versus placebo, including both ‘moderately better’ and ‘much better’ responses (Figure 3).
The number of PGI-C VMS responders (those indicating they felt ‘much better’, the highest response category) was greater for fezolinetant than for placebo.
- At Week 4, the number of PGI-C VMS responders was 140 of 319 (43.9%) in the fezolinetant 45 mg group and 57 of 311 (18.3%) for placebo.
- At Week 12, 47.5% (144/303 women) in the fezolinetant 45 mg group were responders compared with 23.9% (70/293 women) in the placebo group.

Figure 3: PGI-C VMS distribution at Week 4 and 12¹

Week 4:

Week 12:

p < 0.001 for fezolinetant 30 mg versus placebo and for fezolinetant 45 mg versus placebo at Weeks 4 and 12. Pvalues were obtained using Cochran-Mantel-Haenszel test with modified ridit scores. Adapted from: Cano A, BJOG 2024

DAYLIGHT data^2,6

Figure 4. Change from baseline to Week 24 in MENQoL Total Score^a²

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 Scores²

At Week 24, the most common response was ‘much better’ on the PGI-C VMS in participants receiving fezolinetant (62.4% [123/197 women] in the fezolinetant group versus 39.9% [71/178 women] in the placebo group) (Figure 6).

Figure 6. PGI-C VMS distribution at Week 24⁶

All randomized participants assessed according to the randomization at first dose (fezolinetant 45 mg n = 226; placebo n = 226). Adapted from: Schaudig K, BMJ 2024.

Phase 4 real-world study, OPTION-VMS, preliminary results^3,4

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).^3–5,7
- 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.⁴ 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:⁵
- 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.

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.
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.
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.
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.
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.
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.
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.