Nonhormonal neurokinin 3 receptor antagonist (NK3R) fezolinetant significantly reduces vasomotor symptoms in women with menopause, according to study results published in the Lancet.
Fezolinetant may serve as a potential alternative to those who are unable to or do not wish to use hormonal therapy for vasomotor symptoms associated with menopause.
Researchers conducted a randomized, double-blind, placebo-controlled phase 3 study (SKYLIGHT 1; ClinicalTrials.gov Identifier: NCT04003155) over a period of 12 weeks to investigate the safety and efficacy of fezolinetant in the treatment of moderate to severe vasomotor symptoms in menopause.
Women aged between 40 and 65 years who had an average of 7 or more moderate to severe hot flashes per day were included in the study. Inclusion criteria were clinical menopause or spontaneous amenorrhea of more than 6 months with biochemical criteria of menopause.
Participants were randomly assigned 1:1:1 to receive placebo, fezolinetant 30 mg once-daily, or fezolinetant 45 mg once-daily.
Data were collected using an electronically interactive self-reported hot flashes diary that was available 24 hours a day.
Coprimary endpoints included mean change in frequency and severity of symptoms. Key secondary endpoint was the average change in quality of sleep, measured using the Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS SD SF 8b).
In total, 2205 women were enrolled in the study; 527 were randomly assigned to treatment groups (175 received placebo, 173 received fezolinetant 45 mg, and 174 received fezolinetant 30 mg).
Women who received fezolinetant 30 mg had a reduction in mean frequency of daily moderate to severe vasomotor events from 10.7 events per 24 hours at baseline to 5.4 events per 24 hours at week 4 and 4.5 events per 24 hours at week 12 (mean percentage change from baseline, -48% at week 4 and -56% at week 12).
Women who received fezolinetant 45 mg had a reduction in mean frequency of daily moderate to severe vasomotor symptoms from 10.4 events per 24 hours at baseline to 5.2 events per 24 hours at week 4 and 4.1 events per 24 hours at week 12 (mean percentage change, -51% at week 4 and -61% at week 12).
Researchers did not observe significant changes in improvements in patient-reported sleep disturbances at 12 weeks.
One of the study limitations was the lack of inclusion of other menopausal symptoms with fezolinetant treatment.
The study authors concluded, “NK3R antagonists have the potential to provide alternative non-hormonal treatment options to address the unmet need for many women who have vasomotor symptoms.”
Disclosure: This research was supported by Astellas Pharma. Mulitple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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(10382):1091-1102. doi:10.1016/S0140-6736(23)00085-5