5092 Effect of Fezolinetant Treatment on Patient-Reported Outcomes: Data from Phase 3b study (DAYLIGHT) for Moderate-To-Severe Vasomotor Symptoms Associated with Menopause in Women Considered Unsuitable for Hormone Therapy
Authors: Shapiro C.M. Marla , Wu Xi , Wang Xuegong , Miyazaki Kentaro , Morga Antonia , Nappi Rosella E , Stute Petra , Martins Karla , Schaudig Katrin 
Published: October 2024

Disclosure: M. Shapiro C.M.: Advisory Board Member; Self; Aspen, Astellas, Bayer, BioSyent, Duchesnay, GlaxoSmithKline, Merck, Mithra, Pfizer, Searchlight, Sprout, Sunovion, Therapeutics, Inc.. Consulting Fee; Self; Aspen, Astellas, Bayer, BioSyent, Duchesnay, GlaxoSmithKline, Merck, Mithra, Pfizer, Searchlight, Sprout, Sunovion, Therapeutics, Inc.. Other; Self; fulfils a leadership or fiduciary role for the International Menopause Society, fulfils a leadership or fiduciary role for Research Canada, fulfils a leadership or fiduciary role for Terry Fox Research Institute, Inc., This study was funded by Astellas Pharma Inc. Medical writing support was provided by Yien Liu from Envision Pharma, Inc. and funded by the study sponsor. X. Wu: Employee; Self; Astellas Pharma Inc. X. Wang: Employee; Self; Astellas Pharma Inc. K. Miyazaki: Employee; Self; Astellas Pharma Inc. A. Morga: Employee; Self; Astellas Pharma Inc. R.E. Nappi: Other; Self; past financial relationships (lecturer, member of advisory boards, and/or consultant) with Boehringer Ingelheim, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Eli Lilly, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Endoceutics, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Exeltis, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Novo Nordisk, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Palatin Technologies, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Pfizer, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Procter & Gamble, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Teva Women's Health, past financial relationships (lecturer, member of advisory boards, and/or consultant) with Zombon, ongoing relationships with Abbott, ongoing relationships with Astellas, ongoing relationships with Bayer HealthCare, ongoing relationships with Fidia, ongoing relationships with Gedeon Richter, ongoing relationships with HRA Pharma, ongoing relationships with Merck & Co, ongoing relationships with Organon, ongoing relationships with Shionogi, ongoing relationships with Theramex, ongoing relationships with Viatris, President Elect of the International Menopause Society. P. Stute: Consulting Fee; Self; Astellas. Speaker; Self; Bayer HealthCare, Besins Healthcare, Effik, Exeltis, Gedeon Richter, Jenapharm, Labatec, Pharmacosmos, Theramex, Zeller. Other; Self; board member for the Deutsche Menopause Gesellschaft and the European Menopause and Andropause Society, President of the Swiss Society for Gynecological Endocrinology and Menopause. K. Martins: Employee; Self; Astellas Pharma Inc. K. Schaudig: Other; Self; Consultant and lecturer for aidhere, Consultant and lecturer for Astellas, Consultant and lecturer for Bayer HealthCare, Consultant and lecturer for Besins Healthcare, Consultant and lecturer for Exeltis, Consultant and lecturer for Gedeon Richter, Consultant and lecturer for Jenapharm, Consultant and lecturer for Mylan, Consultant and lecturer for Novo Nordisk, Consultant and lecturer for Organon, Consultant and lecturer for Theramex, Consultant and lecturer for Viatris, Consultant and lecturer for Laborarztpraxis Rhein-Main, President of the German Menopause Society (Deutsche Menopause Gesellschaft e.V.).

Introduction: Vasomotor symptoms (VMS) associated with menopause can significantly impact health-related qualify of life (QoL). Fezolinetant is a nonhormonal, selective neurokinin 3 receptor antagonist that is approved in the US for the treatment of moderate-to-severe VMS due to menopause. Objective: To report patient-reported QoL outcomes in the 24-week placebo-controlled DAYLIGHT study. Methods: DAYLIGHT (NCT05033886) was a phase 3b, randomised, double-blind, 24-week placebo-controlled study. Participants were women aged ≥40 to ≤65 years with moderate-to-severe VMS who were unsuitable for HT based on contraindications, caution (prior medical history), stoppers (lack of efficacy, side effects, or medical advice), or averse (made informed choice not to take HT after discussion with clinician), randomised 1:1 to placebo or fezolinetant 45 mg once daily. The primary endpoint was mean change in daily VMS frequency of moderate-to-severe episodes from baseline to Week 24. Secondary endpoints included patient-reported sleep disturbance (Patient-Reported Outcomes Measurement Information System Sleep Disturbance – Short Form 8b [PROMIS SD SF 8b]. Exploratory endpoints measured QoL improvements with patient-reported outcomes of sleep disturbance (PGI-S/PGI-C SD, MENQOL) and VMS (PGI-C VMS, WPAI VMS). Treatment policy estimand was used for all exploratory efficacy endpoint analyses. Results Overall, 453 women were enrolled (placebo n=226; fezolinetant n=227), including HT contraindicated (51, 11%), caution (165, 36%), stoppers (69, 15%), and averse (168, 37%). DAYLIGHT results met the primary objective showing statistically significant reduction from baseline in the frequency of moderate-to-severe VMS to week 24 for fezolinetant 45 mg once daily versus placebo. Through week 24, no safety signals of concern were apparent for 45 mg fezolinetant dose. At week 24, statistically significant improvements from baseline were seen in the fezolinetant 45 mg group compared to placebo in PROMIS SD SF 8b total score (least squares [LS] mean difference: –2.5; 95% CI –3.9, –1.1; p&lt;0.001), MENQOL total score (LS mean difference: –0.44; 95% CI –0.69, –0.18; p&lt;0.001), and WPAI-VMS (activity impairment [p&lt;0.001], overall work productivity loss [p=0.036], and presenteeism [p=0.002] domains). A higher proportion of participants in the fezolinetant group reported positive changes in sleep disturbance (PGI-C SD, p&lt;0.001), sleep disturbance severity (PGI-S SD, p=0.042), and VMS (PGI-C VMS, p&lt;0.001) compared to placebo at week 24. Conclusions: DAYLIGHT is the first study of fezolinetant to investigate efficacy versus placebo over 24 weeks. Fezolinetant 45 mg was efficacious and well tolerated for moderate-to-severe VMS in women considered unsuitable for HT. A range of patient-reported outcomes demonstrate that reductions in VMS frequency with fezolinetant treatment led to improvements in QoL.

Presentation: 6/3/2024