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 these studies during the double-blind periods.^1,2

Note that 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.

Pooled SKYLIGHT 1 and 2 data

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 VMS

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

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 24³

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.

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; Available at: https://doi.org/10.1111/1471-0528.17773.
Shapiro M, 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; Available at: https://doi.org/10.1016/j.maturitas.2024.108159.
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 (Clin. Res. ed). 2024;387:e079525. Available at: https://doi.org/10.1136/bmj-2024-079525.