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. 2025 May 23;32(6):488–498. doi: 10.1097/GME.0000000000002532

Treating moderate to severe menopausal vasomotor symptoms with fezolinetant: responder analysis of the phase 3b DAYLIGHT study

Marla Shapiro 1, Katrin Schaudig 2, Angelica Lindén Hirschberg 3, Martin Blogg 4, Antonia Morga 4, Karla Martins 4, Céline Bouchard 5,✉
PMCID: PMC12097698

Abstract

Objectives:

To characterize the efficacy of fezolinetant for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause using responder analyses of VMS frequency, patient-reported outcomes (PROs) of quality of life (QOL), and time to response.

Methods:

Prespecified analysis of DAYLIGHT (NCT05033886), a phase 3b, randomized, double-blind, 24-week, placebo-controlled study of fezolinetant in women considered unsuitable for hormone therapy. Two approaches for responder analyses: (1) participants with change from baseline in the frequency of moderate to severe VMS of ≥50%, ≥75%, and 100%, and (2) participants who experienced a clinically meaningful within-patient change (not placebo adjusted) compared with baseline in 1, 2, or 3 specified combinations of VMS frequency and PROs: the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b total score, Menopause-Specific QOL total score, and Menopause-Specific QOL Vasomotor domain score. P values were nominal and not controlled for multiplicity.

Results:

Overall, 453 participants were randomized (placebo n = 226; fezolinetant 45 mg n = 227), and 370 (81.9%) of these completed the study (n = 175; n = 195, respectively). The full analysis set comprised 452 participants (placebo n = 226; fezolinetant 45 mg n = 226). Of these, 387 (85.6%) participants completed the 24-week treatment period. The proportion of participants with ≥50%, ≥75%, and 100% reductions in VMS frequency was higher in the fezolinetant 45 mg group than placebo throughout the treatment period. Week 24 odds ratio (OR) comparisons: ≥50% reduction: fezolinetant 45 mg: 60.6% versus placebo: 46.0%; OR: 1.82; 95% CI: 1.25 to 2.65; P = 0.002; ≥75% reduction: fezolinetant 45 mg: 46.9% versus placebo: 29.6%; OR: 2.10; 95% CI: 1.43 to 3.10; P < 0.001; 100% reduction: fezolinetant 45 mg: 22.1% versus placebo: 10.6%; OR: 2.39; 95% CI: 1.42 to 4.10; P = 0.001. Reductions in VMS frequency and severity were seen as early as week 1. A greater proportion of responders was observed in the fezolinetant 45 mg group versus placebo at week 24 in all responder analyses. ORs were supportive of a beneficial effect for fezolinetant 45 mg versus placebo (OR >1) for all PROs.

Conclusions:

Analyses of responders in the DAYLIGHT study showed higher, clinically meaningful responder rates and supported the treatment effect of fezolinetant relative to placebo in women unsuitable for hormone therapy.

Key Words: Clinically meaningful, Fezolinetant, Hot flushes, Menopause, Responder, Vasomotor symptoms

Vasomotor symptoms (VMS), primarily characterized by hot flushes and/or night sweats, affect up to 80% of women during the menopause transition.1,2 The severity and duration of VMS varies with the course of menopause and between women; moderate to severe symptoms are experienced by 11%-46% of women over 40 years of age, with a median total duration of around 7.4 years.3,4,5,6 VMS may persist for more than a decade after the menopause transition.6 Moderate to severe VMS can adversely affect health-related quality of life (QOL), including impact on sleep; concentration; mood; energy; sexual activity; and leisure, social, and work activities.7,8,9 In addition, frequent and persistent VMS are associated with adverse physiological health outcomes, including increased risk for cardiovascular disease and lower bone density.10,11,12

Hormone therapy (HT) is currently the principal treatment for VMS associated with menopause.13,14 However, HT is contraindicated in women with a history of breast cancer or endometrial cancer, stroke, and some thromboembolic diseases.14 Specific caution is also advised in cases of cardiovascular disease, diabetes, or elevated triglyceride levels.14 Many women are unsuitable for HT or choose not to take it due to concerns such as side effects, long-term risks of treatment, and the presence of familial risk factors.13,15

Fezolinetant is approved as a treatment option for moderate to severe VMS in many regions, including North America, Europe, Asia, and Australia at a dose of 45 mg once daily.16,17,18,19,20,21 Fezolinetant blocks neurokinin B signaling, normalizing KNDy neuron activity on the thermoregulatory center of the brain to reduce the frequency and severity of VMS.22,23 Fezolinetant was shown to be efficacious and well tolerated for treating moderate to severe VMS associated with menopause in phase 3 studies SKYLIGHT 1 and SKYLIGHT 2,24,25 which both included a 12-week placebo control followed by active treatment extension through 52 weeks. A prespecified pooled analysis of SKYLIGHT 1 and SKYLIGHT 2 showed the improvements in VMS frequency and severity with fezolinetant treatment over 12 weeks translated into improvements in health-related QOL, as measured by both condition-specific and generic patient-reported outcome (PRO) measures.26 Fezolinetant 45 mg was also shown to be efficacious and well tolerated in the phase 3b study DAYLIGHT, which included a 24-week placebo control period and enrolled a population considered unsuitable for HT.27 Here, we further characterize the efficacy of fezolinetant for the treatment of moderate to severe VMS associated to menopause using responder analyses of VMS frequency, PROs of QOL, and time to response.

METHODS

Study design

DAYLIGHT (NCT05033886) was a phase 3b, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of fezolinetant for treating moderate to severe VMS associated with menopause in women considered unsuitable for HT. DAYLIGHT was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and International Council for Harmonisation guidelines. An Independent Ethics Committee or Institutional Review Board reviewed ethical, scientific, and medical appropriateness of the study before data collection at each site. Written informed consent was obtained from all participants before any study-related procedures.

Participants

DAYLIGHT methodology has been published previously.27 Briefly, women aged 40-65 years with moderate to severe VMS associated with menopause and considered unsuitable for HT were randomized 1:1 to fezolinetant 45 mg or placebo once daily and stratified by smoking status through interactive response technology. Unsuitability for HT was defined as contraindicated, caution (based on prior medical history), stoppers (previously discontinued HT owing to lack of efficacy, side effects, or medical advice), or averse (made informed choice not to take HT after discussion with clinician).

Outcome measures

The current manuscript reports the results of responder analyses from DAYLIGHT. VMS were recorded using an electronic diary; participants were provided with a reference guide for the severity of VMS:

  • Mild: Sensation of heat without sweating.

  • Moderate: Sensation of heat with sweating; able to continue activity.

  • Severe: Sensation of heat with sweating, causing cessation of activity.

PROs of QOL included the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF 8b) total score, Menopause-Specific QOL (MENQOL) total score, and MENQOL Vasomotor domain score. PROMIS is a set of patient-centered instruments used to evaluate physical, mental, and sexual health. The PROMIS SD SF 8b was developed from the PROMIS instrument as a sleep disturbance assessment and is validated for measuring the impact of menopause-associated VMS symptoms.28 The instrument evaluates difficulties with falling asleep, staying asleep, sleep quantity, perceptions of sleep quality, and satisfaction of sleep over the previous 7 days. Total score was calculated by summing the items (range: 8-40; higher scores represent more disturbed sleep). If items were not completed, the score was considered missing. MENQOL is a 29-item PRO measure assessing 4 domains of menopausal symptoms in the past week: vasomotor, psychosocial, physical, and sexual. The MENQOL total score is the mean of the 4 domain scores, which rate symptoms on a scale of 0 (not bothersome) to 6 (extremely bothersome).29

Definitions of response

Two different approaches were used for responder analyses: (1) participants who experienced a percentage change from baseline in the frequency of moderate to severe VMS of ≥50%, ≥75%, and 100%, and (2) participants who experienced a clinically meaningful within-patient change (not placebo adjusted) compared with baseline in 1, 2, or 3 specified outcomes. These responders were classified as: (1) single responders: a clinically meaningful response in either VMS frequency, PROMIS SD SF 8b total score, MENQOL total score, or MENQOL domain score, (2) double responders: a clinically meaningful response in VMS frequency plus 1 PRO (PROMIS SD SF 8b total score, MENQOL total score, or MENQOL Vasomotor domain score), or (3) triple responders: a clinically meaningful response in VMS frequency and PROMIS SD SF 8b total score, combined with either MENQOL total score or MENQOL Vasomotor domain score. We first assessed each of the 3 measures of response for each patient. Then, we analyzed how many patients reached the definition of response for 2 of them (for each of the 3 possible pairs), then how many reached the definition for all 3.

Clinically meaningful responses were defined as: responders of VMS frequency were participants with absolute change from baseline in the frequency of moderate to severe VMS ≤ -6.2 at the analysis visit, responders of PROMIS SD SF 8b total score were participants with change from baseline ≤ -8 at the analysis visit, responders of MENQOL total score were participants with change from baseline ≤ -0.9 at the analysis visit, and responders of MENQOL domain scores were participants with change from baseline to the analysis visit of ≤ -2 for Vasomotor, ≤ -0.9 for Psychosocial, ≤ -0.8 for Physical, and ≤ -1.2 for Sexual.

The anchor-based method was the primary approach used to develop the clinically meaningful thresholds. Anchor methods in PRO analyses involve linking changes in patient scores to an external criterion or “anchor,” such as a patient’s own rating of symptom improvement, to interpret the clinical relevance of score changes and establish thresholds for meaningful improvement. For the purpose of the responder analyses presented in this manuscript, using pooled data from SKYLIGHT 1 and SKYLIGHT 2, Patient Global Impression of Change in VMS (PGI-C VMS) was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency and in MENQOL.30,31 Thresholds for meaningful within-patient change for PROMIS SD SF 8b were estimated using anchor-based approaches, using the Patient Global Impression of Severity in Sleep Disturbance (PGI-S SD) and the PGI-C in Sleep Disturbance (PGI-C SD) as anchors.32 The anchor for clinically meaningful change in VMS frequency was a score of at least moderately better” on the PGI-C VMS. The anchor for clinically meaningful change in PROMIS SD SF 8b was a score of at least “moderately better” on the PGI-C SD and 2-point improvement on PGI-C SD. The anchor for clinically meaningful change in MENQOL was a score of at least “moderately better” on PGI-C VMS.

Endpoints

The DAYLIGHT study's primary efficacy endpoint was a mean change in the daily frequency of moderate to severe VMS episodes from baseline to week 24. Mean change in VMS severity (key secondary endpoint) from baseline to week 24 and safety were also assessed. Prespecified secondary endpoints in DAYLIGHT included a responder analysis defined as the number of participants who experienced a reduction in the frequency of moderate to severe VMS of ≥50%, ≥75%, and 100% from baseline to weeks 1, 4, 8, 12, 16, 20, and 24 (separate classifications at each week). Responder analyses were also prespecified for the number of participants who experienced a clinically meaningful response in 1, 2, or 3 of the selected PROs (single, double, or triple responders) and daily mean changes in the frequency and severity of moderate to severe VMS in the first week of study treatment. Participants who discontinued treatment early were asked to remain in the study and continue to complete the electronic daily VMS diary and electronic PRO assessments as scheduled through week 24.

Statistical analysis

The full analysis set (FAS) was defined as all participants who were randomized and received ≥ 1 dose of study intervention. Participants were analyzed according to the study treatment group to which they were randomized. For the responder analysis (≥50%, ≥75%, and 100%), logistic regression was performed each week, with treatment group and smoking status as factors, and baseline average daily frequency of moderate to severe VMS as a covariate. Kaplan-Meier analysis was used to determine the time to first response for each responder. For the single responder analyses, logistic regression was performed, with treatment group and smoking status (current vs former/never) as factors, and baseline value as a covariate. For the double and triple responder analyses, logistic regression was performed, with treatment group and smoking status (current vs former/never) as factors, and baseline moderate to severe VMS frequency and baseline PRO value as covariates. Daily mean changes in the frequency and severity of moderate to severe VMS from baseline to days 2 to 7 (week 1) were summarized by descriptive statistics. Change from baseline value at each post-baseline day was determined by the treatment group. P values presented for responder analyses here were not controlled for multiplicity and were nominal, and not to be used for inference purposes.

RESULTS

Study participants

DAYLIGHT was conducted at 69 centers that enrolled participants in 16 countries (Canada, the Netherlands, Belgium, France, Spain, Finland, Hungary, Italy, Czech Republic, United Kingdom, Denmark, Sweden, Norway, Poland, Germany, and Turkey). DAYLIGHT was initiated on November 8, 2021, with the last evaluation on April 20, 2023. Overall, 453 participants were randomized (placebo n = 226; fezolinetant 45 mg n = 227), with 370 (81.7%) completing the study (n = 175; n = 195, respectively). The FAS comprised 452 participants (placebo n = 226; fezolinetant 45 mg n = 226), as 1 participant randomized to the fezolinetant group did not receive the study drug.

Of these, 387 (85.6%) participants completed the 24-week treatment period. Baseline demographics and characteristics were generally similar between the placebo and fezolinetant 45 mg groups (Table 1). Mean (SD) age was 54.5 (4.7) years, and most of the participants were White (n = 435, 96.7%). Most participants were either HT averse (n = 168, 37.2%) or HT cautious (n = 165, 36.5%); the remaining were HT contraindicated (n = 50, 11.1%) or HT stoppers (n = 69, 15.3%). The mean (SD) overall drug exposure was 150.8 (44.6) days. Further details on participant demographics, baseline characteristics, primary and secondary endpoints, and safety results have been published previously.27 DAYLIGHT safety data were generally consistent with the known safety profile for fezolinetant.

TABLE 1.

Summary of key demographics and baseline characteristics (FAS)

Placebo (n = 226) Fezolinetant 45 mg (n = 226) Total (N = 452) a
Race, n (%)
 White 218 (97.3) 217 (96.0) 435 (96.7)
 Other b 6 (2.7) 9 (4.0) 15 (3.3)
 Missing 2 0 2
Mean (SD) age (y) 54.1 (4.6) 54.9 (4.8) 54.5 (4.7)
Mean (SD) BMI (kg/m2) 26.98 (4.52) 27.42 (4.33) 27.20 (4.43)
HT unsuitable, n (%)
 Contraindicated 23 (10.2) 27 (11.9) 50 (11.1)
 Caution 91 (40.3) 74 (32.7) 165 (36.5)
 Stoppers 37 (16.4) 32 (14.2) 69 (15.3)
 Averse 75 (33.2) 93 (41.2) 168 (37.2)
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BMI, body mass index; FAS, full analysis set; HT, hormone therapy.

a

N = 453 participants were randomized; 1 participant did not receive the study drug.

b

Non-white or > 1 race.

Responders analyses

A higher proportion of participants had a ≥50% reduction in the frequency of moderate to severe VMS in the fezolinetant 45 mg group than in the placebo group at all visits during the treatment period (Table 2, Fig. 1A). The proportion of participants who had a ≥50% reduction increased from week 1 (fezolinetant 45 mg: 42.0% vs placebo: 14.6%; odds ratio [OR]: 4.38; 95% CI: 2.79 to 7.01; P < 0.001) to week 8 (fezolinetant 45 mg: 65.9% vs placebo: 51.8%; OR: 1.80; 95% CI: 1.23 to 2.64; P = 0.003). This was maintained throughout the treatment period, up to week 24 (fezolinetant 45 mg: 60.6% vs placebo: 46.0%; OR: 1.82; 95% CI: 1.25 to 2.65; P = 0.002). The median time to a ≥50% reduction response (95% CI) was 6 days (5 to 8) in the fezolinetant 45 mg group compared with 17 days (13 to 21) in the placebo group (Fig. 2A).

TABLE 2.

Responders of ≥50%, ≥75%, and 100% reduction from baseline in frequency of moderate to severe VMS (FAS)

Placebo (n = 226) Fezolinetant 45 mg (n = 226)
Week 1
 ≥50%
  Responders, n (%) 33 (14.6) 95 (42.0)
  OR — 4.38
  95% CI (2-sided) — 2.79 to 7.01
  P (2-sided) a — <0.001
 ≥75%
  Responders, n (%) 5 (2.2) 35 (15.5)
  OR — 8.36
  95% CI (2-sided) — 3.49 to 24.82
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 0 NC
  OR — NC
  95% CI (2-sided) — NC
  P (2-sided) a — NC
Week 4
 ≥50%
  Responders, n (%) 100 (44.2) 148 (65.5)
  OR — 2.39
  95% CI (2-sided) — 1.64 to 3.50
  P (2-sided) a — <0.001
 ≥75%
  Responders, n (%) 39 (17.3) 90 (39.8)
  OR — 3.18
  95% CI (2-sided) — 2.07 to 4.96
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 8 (3.5) 18 (8.0)
  OR — 2.37
  95% CI (2-sided) — 1.04 to 5.88
  P (2-sided) a — 0.049
Week 8
 ≥50%
  Responders, n (%) 117 (51.8) 149 (65.9)
  OR — 1.80
  95% CI (2-sided) — 1.23 to 2.64
  P (2-sided) a — 0.003
 ≥75%
  Responders, n (%) 69 (30.5) 104 (46.0)
  OR — 1.94
  95% CI (2-sided) — 1.32 to 2.86
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 17 (7.5) 35 (15.5)
  OR — 2.26
  95% CI (2-sided) — 1.24 to 4.26
  P (2-sided) a — 0.009
Week 12
 ≥50%
  Responders, n (%) 106 (46.9) 154 (68.1)
  OR — 2.42
  95% CI (2-sided) — 1.65 to 3.57
  P (2-sided) a — <0.001
 ≥75%
  Responders, n (%) 66 (29.2) 110 (48.7)
  OR — 2.30
  95% CI (2-sided) — 1.56 to 3.40
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 22 (9.7) 49 (21.7)
  OR — 2.56
  95% CI (2-sided) — 1.51 to 4.49
  P (2-sided) a — <0.001
Week 16
 ≥50%
  Responders, n (%) 107 (47.3) 140 (61.9)
  OR — 1.81
  95% CI (2-sided) — 1.25 to 2.64
  P (2-sided) a — 0.002
 ≥75%
  Responders, n (%) 67 (29.6) 104 (46.0)
  OR — 2.02
  95% CI (2-sided) — 1.37 to 2.99
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 27 (11.9) 50 (22.1)
  OR — 2.09
  95% CI (2-sided) — 1.26 to 3.52
  P (2-sided) a — 0.005
Week 20
 ≥50%
  Responders, n (%) 101 (44.7) 149 (65.9)
  OR — 2.40
  95% CI (2-sided) — 1.65 to 3.53
  P (2-sided) a — <0.001
 ≥75%
  Responders, n (%) 66 (29.2) 109 (48.2)
  OR — 2.28
  95% CI (2-sided) — 1.55 to 3.39
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 27 (11.9) 47 (20.8)
  OR — 1.93
  95% CI (2-sided) — 1.16 to 3.26
  P (2-sided) a — 0.013
Week 24
 ≥50%
  Responders, n (%) 104 (46.0) 137 (60.6)
  OR — 1.82
  95% CI (2-sided) — 1.25 to 2.65
  P (2-sided) a — 0.002
 ≥75%
  Responders, n (%) 67 (29.6) 106 (46.9)
  OR — 2.10
  95% CI (2-sided) — 1.43 to 3.10
  P (2-sided) a — <0.001
 100%
  Responders, n (%) 24 (10.6) 50 (22.1)
  OR — 2.39
  95% CI (2-sided) — 1.42 to 4.10
  P (2-sided) a — 0.001
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FAS, full analysis set; NC, not calculable; OR, odds ratio; VMS, vasomotor symptoms.

All randomized participants took ≥ 1 dose of study intervention. Participants were analyzed according to the study treatment group to which they were randomized (FAS). Participants with missing VMS data at an analysis visit were considered nonresponders. Logistic regression was performed for each of the responders at each week.

a

Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of VMS at baseline as a covariate. An odds ratio of >1 indicates a favorable response in the fezolinetant group. P values were not controlled for multiplicity.

FIG. 1.

FIG. 1

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Proportion of participants with (A) ≥50%, (B) ≥75%, and (C) 100% reduction in the frequency of moderate to severe VMS from baseline to week 24. Participants with missing VMS data at an analysis visit were considered nonresponders. Logistic regression was performed for each of the responders each week. a Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and mean frequency of VMS at baseline as a covariate. P values were not controlled for multiplicity. NC, not calculable; VMS, vasomotor symptoms.

FIG. 2.

FIG. 2

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Time to (A) ≥50%, (B) ≥75%, and (C) 100% reduction in frequency of moderate to severe VMS (FAS). All randomized participants took ≥ 1 dose of study intervention. Participants were analyzed according to the study treatment group to which they were randomized (FAS). Based on Kaplan-Meier estimates stratified by treatment group. The time to response is the first day with ≥50%, ≥75%, or 100% response, respectively, for both the original number and smooth average number, where the smooth average of day X was assigned using the average from day X-1, day X, and day X+1. The censoring time was the number of days from the first dosing date to the last contact date. Nonresponders were censored at the end of treatment. An open circle indicates censoring. FAS, full analysis set; VMS, vasomotor symptoms.

A higher proportion of participants had a ≥75% reduction in the frequency of moderate to severe VMS in the fezolinetant 45 mg group than in the placebo group at all visits during the treatment period (Table 2, Fig. 1B). The proportion of participants who had a ≥75% reduction increased from week 1 (fezolinetant 45 mg: 15.5% vs placebo: 2.2%; OR: 8.36; 95% CI: 3.49 to 24.82; P < 0.001) to week 8 (fezolinetant 45 mg: 46.0% vs placebo: 30.5%; OR: 1.94; 95% CI: 1.32 to 2.86; P < 0.001), and this proportion was maintained throughout the treatment period, up to week 24 (fezolinetant 45 mg: 46.9% vs placebo: 29.6%; OR: 2.10; 95% CI: 1.43 to 3.10; P < 0.001). The median time to a ≥75% reduction response (95% CI) was 18 days (14 to 25) in the fezolinetant 45 mg group compared with 56 days (42 to 79) in the placebo group (Fig. 2B).

A higher proportion of participants had a 100% reduction in the frequency of moderate to severe VMS in the fezolinetant 45 mg group than in the placebo group at all visits during the treatment period except for week 1, where no responders with 100% reduction were observed (Table 2, Fig. 1C). The proportion of participants who had a 100% reduction increased from week 1 with no responders in either treatment group to week 12 (fezolinetant 45 mg: 21.7% vs placebo: 9.7%; OR: 2.56; 95% CI: 1.51 to 4.49; P < 0.001), and this proportion was maintained throughout the treatment period, up to week 24 (fezolinetant 45 mg: 22.1% vs placebo: 10.6%; OR: 2.39; 95% CI: 1.42 to 4.10; P = 0.001). The median time to a 100% reduction response (95% CI) was 131 days (80 to 165) in the fezolinetant 45 mg group and not estimable in the placebo group (Fig. 2C).

Exploratory single/double/triple responder analysis

A greater proportion of responders was observed in the fezolinetant 45 mg group versus the placebo group at week 24 in all single, double, and triple responder analyses (Table 3). ORs were supportive of a beneficial effect for fezolinetant 45 mg versus placebo (OR >1) for PROMIS SD SF 8b total score, MENQOL total score, and all domains of the MENQOL. In the double responder analyses, ORs were supportive of a beneficial effect of fezolinetant 45 mg versus placebo for VMS frequency plus PROMIS SD SF 8b total score (OR: 2.34; 95% CI: 1.42 to 3.93), MENQOL total score (OR: 2.09; 95% CI: 1.33 to 3.30), and MENQOL Vasomotor domain score (OR: 2.62; 95% CI: 1.65 to 4.22; Table 3). Beneficial effects were observed for triple responders based on VMS frequency and PROMIS SD SF 8b total score plus MENQOL total score (OR: 2.21; 95% CI: 1.31 to 3.77), and plus MENQOL Vasomotor domain score (OR: 2.54; 95% CI: 1.50 to 4.39; Table 3).

TABLE 3.

Responder analyses for clinically meaningful thresholds at week 24 (FAS)

Criteria Statistics Placebo (n = 226) Fezolinetant 45 mg (n = 226)
Single responders
 VMS frequency Responders, n (%); 95% CI: 2-sided a 90/164 (54.9); 46.9 to 62.6 124/176 (70.5); 63.1 to 77.1
OR (95% CI: 2-sided) b — 2.02 (1.28 to 3.21)
P (2-sided) b — 0.003
 PROMIS SD SF 8b total score Responders, n (%); 95% CI: 2-sided a 57/178 (32.0); 25.2 to 39.4 97/196 (49.5); 42.3 to 56.7
OR (95% CI: 2-sided) b — 2.00 (1.29 to 3.13)
P (2-sided) b — 0.002
 MENQOL total score Responders, n (%); 95% CI: 2-sided a 103/176 (58.5); 50.9 to 65.9 135/196 (68.9); 61.9 to 75.3
OR (95% CI: 2-sided) b — 1.58 (1.02 to 2.46)
P (2-sided) b — 0.042
 MENQOL Vasomotor domain score Responders, n (%); 95% CI: 2-sided a 94/176 (53.4); 45.8 to 60.9 136/196 (69.4); (62.4 to 75.8)
OR (95% CI: 2-sided) b — 2.11 (1.35 to 3.31)
P (2-sided) b — 0.001
Double responders
 VMS frequency and PROMIS SD SF 8b total score Responders, n (%); 95% CI: 2-sided a 34/155 (21.9); 15.7 to 29.3 69/167 (41.3); 33.8 to 49.2
OR (95% CI: 2-sided) b — 2.34 (1.42 to 3.93)
P (2-sided) b — 0.001
 VMS frequency and MENQOL total score Responders, n (%); 95% CI: 2-sided a 61/153 (39.9); 32.1 to 48.1 96/167 (57.5); 49.6 to 65.1
OR (95% CI: 2-sided) b — 2.09 (1.33 to 3.30)
P (2-sided) b — 0.002
 VMS frequency and MENQOL Vasomotor domain score Responders, n (%); 95% CI: 2-sided a 60/153 (39.2); 31.4 to 47.4 102/167 (61.1); 53.2 to 68.5
OR (95% CI: 2-sided) b — 2.62 (1.65 to 4.22)
P (2-sided) b — <0.001
Triple responders
 VMS frequency, PROMIS SD SF 8b total score, and MENQOL total score Responders, n (%); 95% CI: 2-sided a 31/153 (20.3); 14.2 to 27.5 62/167 (37.1); 29.8 to 44.9
OR (95% CI: 2-sided) b — 2.21 (1.31 to 3.77)
P (2-sided) b — 0.003
 VMS frequency, PROMIS SD SF 8b total score, and MENQOL Vasomotor domain score Responders, n (%); 95% CI: 2-sided a 31/153 (20.3); 14.2 to 27.5 65/167 (38.9); 31.5 to 46.8
OR (95% CI: 2-sided) b — 2.54 (1.50 to 4.39)
P (2-sided) b — <0.001
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FAS, full analysis set; MENQOL, Menopause-Specific Quality of Life; OR, odds ratio; PROMIS SD SF 8b, Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b; VMS, vasomotor symptoms.

Responders of VMS frequency were participants with absolute change from baseline in the frequency of moderate to severe VMS ≤6.2 at the analysis visit. Responders of PROMIS SD SF 8b total score were participants with change from baseline ≤ -8 at the analysis visit (a negative change indicates a reduction in sleep disturbance). Responders of MENQOL total score were participants with change from baseline ≤ -0.9 at the analysis visit (a negative change indicates a better outcome). Responders of MENQOL domain scores were participants with change from baseline to the analysis visit of ≤ -2 for Vasomotor, ≤ -0.9 for Psychosocial, ≤ -0.8 for Physical, and ≤ -1.2 for Sexual (negative changes indicate better outcomes). Participants with missing response at the analysis visit were reported as missing.

a

95% CI calculated using Clopper-Pearson exact method for binomial proportion.

b

Based on logistic regression with treatment group and smoking status (current vs former/never) as factors and baseline moderate to severe VMS frequency and baseline patient-reported outcome value as covariates. An odds ratio of > 1 indicates a favorable response in the fezolinetant group. P values were not controlled for multiplicity.

Time to response—vasomotor symptom frequency

As reported previously,27 fezolinetant 45 mg significantly reduced VMS frequency (primary endpoint, least squares [LS] mean difference: -1.93; 95% CI: -2.64 to -1.22; P < 0.001) versus placebo at 24 weeks (Fig. 3A). Reductions in VMS frequency were seen as early as day 1 in the fezolinetant 45 mg group. Participants treated with fezolinetant 45 mg had a greater reduction from baseline in the daily mean change in frequency of moderate to severe VMS compared with placebo during the first week of treatment (day 7 LS mean difference: -2.20; 95% CI: -2.78 to -1.61; P < 0.001; Fig. 3A). VMS frequency consistently decreased from days 1 to 6, with the strongest decrease during the first 3 days of treatment.

FIG. 3.

FIG. 3

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(A) Frequency and (B) severity of moderate to severe VMS over 24 weeks and over week 1. VMS, vasomotor symptoms.

Time to response ‐ vasomotor symptom severity

VMS severity was lower in fezolinetant 45 mg versus placebo at 24 weeks (LS mean difference: -0.39; 95% CI: -0.57 to -0.21; P < 0.001; Fig. 3B). Reductions in VMS severity were seen as early as week 1 in the fezolinetant 45 mg group. Participants treated with fezolinetant 45 mg had a greater reduction from baseline in the daily mean change in VMS severity compared with placebo from days 2 to 7 (day 7 LS mean difference: -0.17; 95% CI: -0.23 to -0.10; P < 0.001; Fig. 3B). VMS severity continuously decreased from days 2 to 3 of treatment, remained on the same level on days 4 and 5, decreased again on day 6, and remained on the same level on day 7.

DISCUSSION

The impact of VMS on QOL can be substantial, and VMS are the primary driver for seeking medical attention for menopause-related symptoms.33 Moderate to severe VMS can result in sleep problems, fatigue, anxiety, depression, reduced work productivity, and ability to carry out day-to-day activities.6,7,8,9 DAYLIGHT is the first fezolinetant study to provide placebo-controlled efficacy data over a 24-week period, compared with 12 weeks in the SKYLIGHT studies.24,25 DAYLIGHT is also the first fezolinetant study enrolling participants specifically considered unsuitable for HT.27 Primary data from the DAYLIGHT study showed that fezolinetant 45 mg was efficacious and well tolerated as a treatment for moderate to severe VMS in women considered unsuitable for HT.27

In this current analysis of secondary and exploratory endpoints from DAYLIGHT, participants in the fezolinetant 45 mg group experienced a rapid and sustained reduction in the frequency and severity of VMS and also showed higher responder rates compared with placebo based on within-patient changes in PRO. Reductions in VMS frequency were seen as early as week 1, with the strongest decrease during the first 3 days of treatment. A reduction of at least 50% in VMS frequency at week 12 was achieved by 21.2% more participants who received fezolinetant 45 mg than those who received a placebo. This is comparable with a 23% difference between fezolinetant 45 mg-treated and placebo-treated participants at week 12 in a pooled analysis of the phase 3 SKYLIGHT 1 and SKYLIGHT 2 studies.26 A 100% reduction in VMS frequency was experienced by 12.0% more participants treated with fezolinetant 45 mg versus placebo at 12 weeks, compared with 8% in the pooled SKYLIGHT 1 and SKYLIGHT 2 analysis.26 This 100% reduction in VMS frequency was maintained through to week 24, with 11.5% more participants who received fezolinetant 45 mg versus placebo achieving a 100% reduction in VMS frequency.

The responder analyses in the DAYLIGHT study used clinically meaningful response thresholds derived from pooled data of 2 placebo-controlled fezolinetant studies (SKYLIGHT 1 and 2).30,31,32 These studies included participants not restricted to those for whom HT was unsuitable for menopause-related VMS and also evaluated a lower 30 mg dose of fezolinetant. The clinically meaningful response thresholds were originally based on changes observed at week 12 in the SKYLIGHT trials but were applied to week 24 endpoints in the DAYLIGHT study. These factors likely result in conservative estimates for the responder analyses in DAYLIGHT.

Consistent with previous studies, responses were observed in a proportion of placebo-treated participants, albeit at a lower rate than those receiving fezolinetant. As discussed previously, the reasons for these placebo responses are not fully understood, and it is currently unclear whether the benefits of placebo reflect nonspecific effects, natural history, or statistical phenomena.26 Analysis of patient-reported QOL outcomes from DAYLIGHT further supports the effect of fezolinetant in reducing the burden of VMS and improving QOL for participants with VMS associated with menopause.34 DAYLIGHT PRO results are consistent with previous phase 3 fezolinetant studies showing the beneficial effects of fezolinetant versus placebo on PROMIS SD SF 8b, PGI-S SD, PGI-C SD, PGI-C VMS, and MENQOL.24,25,34,35

A large majority of DAYLIGHT participants are European and Canadian and identify as White, which may be a potential limitation. An analysis of intrinsic and extrinsic factors using pooled data from phase 3 SKYLIGHT studies showed no reduction of fezolinetant efficacy in participants who identified as Black or Hispanic/Latina.36 Future studies of fezolinetant in global, more diverse populations are of interest. As these analyses were not handled within a multiplicity framework and most of them were analyses of exploratory endpoints, P values should be considered unadjusted or nominal and should not be used for inference.

HT to treat VMS can be contraindicated and complicate the treatment decision-making process, and many women can be HT-cautious or HT-averse despite being eligible for treatment.37 There is a need for safe and effective nonhormone treatment options for VMS associated with menopause. This analysis further characterizes the efficacy of fezolinetant for the treatment of moderate to severe VMS associated with menopause using a distinctive approach to assess outcomes and responses. The available evidence from DAYLIGHT highlights the utility of fezolinetant as an effective nonhormone treatment option to reduce VMS frequency and severity and improve QOL in women who cannot or choose not to receive HT.

CONCLUSIONS

DAYLIGHT is the first study of fezolinetant to investigate efficacy versus placebo over 24 weeks. Participants in the fezolinetant 45 mg group showed rapid and sustained reduction in the VMS frequency and severity, as well as higher, clinically meaningful responder rates compared with placebo based on within-patient changes in PROs. Analyses of responders in the DAYLIGHT study supports the treatment effect of fezolinetant relative to placebo.

ACKNOWLEDGMENTS

The authors thank the DAYLIGHT study investigators and all patients and their parents/legal representatives who took part in the study.

Footnotes

Funding/support: This study was funded by Astellas Pharma Inc. Medical writing support was provided by Samantha Coates, PhD, and Yien Liu, PhD, from Envision Pharma Ltd (Fairfield, CT, USA) and funded by the study sponsor.

Financial disclosure/conflicts of interest: M.S.C.M. sits on advisory boards for and has received consulting fees and honorariums from Amgen, Aspen, Astellas, BioSyent, Bayer, CCRN, Duchesnay, Eisai, GSK, Idorsia, Merck, Mithra, Novo Nordisk, Organon, Pfizer, Sandoz, and Searchlight; receives support for attending meetings and/or travel from Astellas and The Menopause Society; has a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for the International Menopause Society and Terry Fox Research Institute. K.S. has received payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from aidhere, Astellas Pharma, Bayer/Jenapharm, Besins Healthcare, Exeltis, Fidia, Gedeon Richter Pharma, Novo Nordisk, Organon, Theramex, Viatris, and Laborarztpraxis Rhein-Main; participates on a data safety monitoring board or advisory board for Astellas, Bayer, Exeltis, Besins Healthcare, and Viatris; is President of the German Menopause Society (organizes and lectures at conferences for the society); lectures and participates in conferences for the professional association of gynecologists in Germany; is honorary member for the German Society of Obstetrics and Gynecology and lectures, is president at conferences, and participates on committees for the society. A.L.H. receives consulting fees from Astellas. M.B., A.M., and K.M. are employees of Astellas Pharma. C.B. has received research grants from Astellas, Mithra, Exeltis, and Incyte; consulting fees from AbCellera; payments or honorariums for speakers bureaus from Bayer and Astellas; payments or honorariums for lectures from Biosyent and Lupin Pharma; support for meeting and traveling for poster session from Searchlight; and participates on advisory boards for Astellas, Bayer, Eisai, and Orimed.

Data sharing statement: Details for how researchers may request access to anonymized participant level data, trial level data, and protocols from Astellas sponsored clinical trials can be found at http://www.clinicaltrials.astellas.com/transparency/.

Sections of the results of this study have been previously presented in oral platform format at The Menopause Society’s 2024 Annual Meeting, Chicago, IL, September 10-14, 2024.

Contributor Information

Marla Shapiro, Email: marlamd@aol.com.

Katrin Schaudig, Email: schaudig@hormone-hamburg.de.

Angelica Lindén Hirschberg, Email: angelica.hirschberg.linden@ki.se.

Martin Blogg, Email: martin.blogg@astellas.com.

Antonia Morga, Email: antonia_morga@astellas.com.

Karla Martins, Email: karla.martins@astellas.com.

Céline Bouchard, Email: celinebouchard2@gmail.com.

REFERENCES

  • 1. Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women’s health across the nation. Am J Public Health 2006;96:1226‐1235. doi: 10.2105/AJPH.2005.066936 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Williams RE, Kalilani L, DiBenedetti DB, et al. Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States. Climacteric 2008;11:32‐43. doi: 10.1080/13697130701744696 [DOI] [PubMed] [Google Scholar]
  • 3. Whiteley J, Wagner JS, Bushmakin A, Kopenhafer L, Dibonaventura M, Racketa J. Impact of the severity of vasomotor symptoms on health status, resource use, and productivity. Menopause 2013;20:518‐524. doi: 10.1097/GME.0b013e31827d38a5 [DOI] [PubMed] [Google Scholar]
  • 4. Blumel JE, Chedraui P, Baron G, et al. A large multinational study of vasomotor symptom prevalence, duration, and impact on quality of life in middle-aged women. Menopause 2011;18:778‐785. doi: 10.1097/gme.0b013e318207851d [DOI] [PubMed] [Google Scholar]
  • 5. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause 2014;21:924‐932. doi: 10.1097/GME.0000000000000196 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175:531‐539. doi: 10.1001/jamainternmed.2014.8063 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 2009;62:153‐159. doi: 10.1016/j.maturitas.2008.12.006 [DOI] [PubMed] [Google Scholar]
  • 8. Worsley R, Bell RJ, Gartoulla P, Robinson PJ, Davis SR. Moderate-severe vasomotor symptoms are associated with moderate-severe depressive symptoms. J Womens Health (Larchmt) 2017;26:712‐718. doi: 10.1089/jwh.2016.6142 [DOI] [PubMed] [Google Scholar]
  • 9. Ayers B, Hunter MS. Health-related quality of life of women with menopausal hot flushes and night sweats. Climacteric 2013;16:235‐239. doi: 10.3109/13697137.2012.688078 [DOI] [PubMed] [Google Scholar]
  • 10. Thurston RC, Aslanidou Vlachos HE, Derby CA, et al. Menopausal vasomotor symptoms and risk of incident cardiovascular disease events in SWAN. J Am Heart Assoc 2021;10:e017416. doi: 10.1161/JAHA.120.017416 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. El Khoudary SR, Greendale G, Crawford SL, et al. The menopause transition and women’s health at midlife: a progress report from the Study of Women’s Health Across the Nation (SWAN). Menopause 2019;26:1213‐1227. doi: 10.1097/GME.0000000000001424 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Biglia N, Cagnacci A, Gambacciani M, Lello S, Maffei S, Nappi RE. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017;20:306‐312. doi: 10.1080/13697137.2017.1315089 [DOI] [PubMed] [Google Scholar]
  • 13. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013;310:1353‐1368. doi: 10.1001/jama.2013.278040 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975‐4011. doi: 10.1210/jc.2015-2236 [DOI] [PubMed] [Google Scholar]
  • 15. Nappi RE, Kroll R, Siddiqui E, et al. Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden. Menopause 2021;28:875‐882. doi: 10.1097/GME.0000000000001793 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. European Medicines Agency. Annex I: summary of product characteristics. Accessed March 25, 2024. https://www.ema.europa.eu/en/documents/product-information/veoza-epar-product-information_en.pdf
  • 17. Medicines and Healthcare Products Regulatory Agency. Public assessment report. Accessed May 14, 2024. https://mhraproducts4853.blob.core.windows.net/docs/452eebb63cf697a3a4bea8b85ed6effbfa0f7332
  • 18. Therapeutic Goods Administration. Australian product information - Veoza™ (fezolinetant). Accessed March 25, 2024. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2024-PI-01388-1&d=20240314172310101
  • 19. US Food and Drug Administration. Highlights of prescribing information. Accessed December 20, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216578s004lbl.pdf
  • 20. Astellas Pharma (Thailand) Co. L. Veoza. National Drug Information. Accessed February 3, 2025. https://ndi.fda.moph.go.th/uploads/drug_detail_corporation/doc/word/1263/7c4b97727e0e458e6b8908689db94332-a1.pdf
  • 21. Veozah. Product Monograph. Accessed March 14, 2025. https://pdf.hres.ca/dpd_pm/00077931.PDF .
  • 22. Depypere H, Lademacher C, Siddiqui E, Fraser GL. Fezolinetant in the treatment of vasomotor symptoms associated with menopause. Expert Opin Investig Drugs 2021;30:681‐694. doi: 10.1080/13543784.2021.1893305 [DOI] [PubMed] [Google Scholar]
  • 23. Astellas Pharma US I VEOZAHTM . Highlights of prescribing information. Accessed August 31, 2023. https://www.astellas.com/us/system/files/veozah_uspi.pdf
  • 24. 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 Endocrinol Metab 2023;108:1981‐1997. doi: 10.1210/clinem/dgad058 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. 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;401:1091‐1102. doi: 10.1016/s0140-6736(23)00085-5 [DOI] [PubMed] [Google Scholar]
  • 26. Nappi RE, Johnson KA, Stute P, et al. Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2). Menopause 2024;31:512‐521. doi: 10.1097/GME.0000000000002354 [DOI] [PubMed] [Google Scholar]
  • 27. Schaudig K, Wang X, Bouchard C, et al. Efficacy and safety of fezolinetant for the treatment of moderate to severe vasomotor symptoms associated with menopause in individuals considered unsuitable for hormone therapy: the phase 3b randomized DAYLIGHT study. BMJ 2024;387:e079525. doi:10.1136/bmj-2024-079525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. English M, Stoykova B, Slota C, et al. Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS sleep disturbance and sleep-related impairment measures for assessment of VMS impact on sleep. J Patient Rep Outcomes 2021;5:37. doi: 10.1186/s41687-021-00289-y [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29. Hilditch JR, Lewis J, Peter A, et al. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas 1996;24:161‐175. doi: 10.1016/s0378-5122(96)82006-8 [DOI] [PubMed] [Google Scholar]
  • 30. Morga A, Zimmermann L, Valluri U, Siddiqui E, McLeod L, Bender RH. Validation and application of thresholds to define meaningful change in vasomotor symptoms frequency: analysis of pooled SKYLIGHT 1 and 2 data. Adv Ther 2024;41:2845‐2858. doi: 10.1007/s12325-024-02849-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31. Schultz NM, Morga A, Siddiqui E, Rhoten SE. Psychometric evaluation of the MENQOL instrument in women experiencing vasomotor symptoms associated with menopause. Adv Ther 2024;41:2233‐2252. doi: 10.1007/s12325-024-02787-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Schultz NM, Morga A, Siddiqui E, Rhoten SE. Psychometric evaluation of the PROMIS SD SF 8b instrument in individuals experiencing vasomotor symptoms due to menopause. Health Qual Life Outcomes 2023;21:126. doi: 10.1186/s12955-023-02206-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Williams RE, Kalilani L, DiBenedetti DB, Zhou X, Fehnel SE, Clark RV. Healthcare seeking and treatment for menopausal symptoms in the United States. Maturitas 2007;58:348‐358. doi: 10.1016/j.maturitas.2007.09.006 [DOI] [PubMed] [Google Scholar]
  • 34. Shapiro CMM, Wu X, Wang X, 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. Maturitas 2025;193:108159. doi:10.1016/j.maturitas.2024.108159. [DOI] [PubMed] [Google Scholar]
  • 35. 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 2024;131:1296-1305. doi:10.1111/1471-0528.17773. [DOI] [PubMed] [Google Scholar]
  • 36. 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;31:247‐257. doi: 10.1097/gme.0000000000002340 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Nappi RE, Siddiqui E, Todorova L, Rea C, Gemmen E, Schultz NM. Prevalence and quality-of-life burden of vasomotor symptoms associated with menopause: a European cross-sectional survey. Maturitas 2023;167:66‐74. doi: 10.1016/j.maturitas.2022.09.006 [DOI] [PubMed] [Google Scholar]

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