Early response with fezolinetant treatment of moderate-to-severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy: phase 3b daylight study

Hirschberg Angelica Linden; Celine Bouchard; Antonio Cano; Katrin Schaudig; Karla Martins; Kentaro Miyazaki; Xi Wu; Xuegong Wang

doi:10.1530/endoabs.99.P352

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Endocrine Abstracts (2024) 99 P352 | DOI: 10.1530/endoabs.99.P352

ECE2024 Poster Presentations Reproductive and Developmental Endocrinology (45 abstracts)

Early response with fezolinetant treatment of moderate-to-severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy: phase 3b daylight study

Angelica Lindén Hirschberg ¹ , Céline Bouchard ² , Antonio Cano ³ , Katrin Schaudig ⁴ , Karla Martins ⁵ , Kentaro Miyazaki ⁶ , Xi Wu ⁷ & Xuegong Wang ⁷

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¹Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; ²Clinique de Recherche en Santé de la Femme, Quebec City, Canada; ³University of Valencia, Valencia, Spain; ⁴Hormone Hamburg, Hamburg, Germany; ⁵Astellas Pharma Europe Ltd, Addlestone, United Kingdom; ⁶Astellas Pharma Inc., Tokyo, Japan; ⁷Astellas Pharma Global Development, Northbrook, IL, United States

Introduction: There is a need for well tolerated and effective nonhormonal therapies for vasomotor symptoms (VMS) associated with menopause. Fezolinetant is a nonhormonal, selective neurokinin 3 receptor antagonist that is approved for the treatment of moderate-to-severe VMS associated with menopause.

Objective: To assess how early a response to fezolinetant in frequency and severity of moderate-to-severe VMS was observed 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 hormone therapy (HT) based on four categories - 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) - and 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. Mean change in VMS severity (key secondary endpoint) and safety were also assessed.

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%). 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 least squares [LS] mean difference: –2.20; 95% CI: –2.78, –1.61; P<0.001). VMS frequency consistently decreased from days 1 to 6, with the strongest decrease during the first 3 days. 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, –0.10; P<0.001). Improvements in VMS frequency and severity were sustained through week 24. No safety signals of concern were apparent for the 45 mg fezolinetant dose through week 24.

Conclusions: Daylight is the first study of fezolinetant to investigate efficacy vs placebo over 24 weeks. Fezolinetant 45 mg was efficacious and well tolerated for moderate-to-severe VMS in women considered unsuitable for HT. An effect on VMS frequency was seen as early as day 1 and maintained through the 24-week placebo-controlled period, demonstrating a rapid onset of action and sustained efficacy with fezolinetant treatment.