medwireNews: Menopausal women with moderate-to-severe vasomotor symptoms (VMS) unsuitable for hormone replacement therapy (HRT) may derive a benefit from fezolinetant for at least 6 months, DAYLIGHT study findings indicate.
The research was presented in a poster at the European Congress of Endocrinology in Stockholm, Sweden, by Antonio Cano, from the INCLIVA Research Institute in Valencia, Spain, and co-authors.
The oral neurokinin 3 receptor antagonist was previously approved for the treatment of moderate-to-severe VMS by the EMA and US FDA on the basis of the SKYLIGHT 1 and 2 trials showing an improvement in both frequency and severity of hot flashes over 12 weeks of use, the researchers explained.
The current phase 3b trial recruited 453 women aged 40 to 65 years (mean 54.5 years; 96.7% White) with moderate-to-severe VMS who were unsuitable candidates for HRT, because of contraindication (11.1%) or prior medical history (36.5%), had stopped HRT due to lack of efficacy or side effects (15.3%), or who had declined HRT after receiving information on the options (37.2%).
The primary endpoint was change in daily frequency of moderate-to-severe VMS episodes between baseline and week 24 of treatment. This was significantly greater among the 226 women who were randomly assigned to receive fezolinetant 45 mg/day, with a mean reduction from 10.58 daily events at baseline to 2.61 at 24 weeks, compared with a reduction from 10.75 to 4.67 daily events among the controls.
This gave a significant least squares mean improvement of 1.93 fewer daily events with fezolinetant than placebo.
In addition, fezolinetant was associated with a significant least squares mean difference of –0.39 in VMS severity over the 24 weeks, with women given the agent experiencing a reduction from 2.43 to 1.43, versus a reduction from 2.41 to 1.87 among the placebo-treated patients.
“Reductions in VMS frequency and severity were seen as early as week 1 in the fezolinetant 45-mg group,” reported Cano and co-workers.
They said exploratory analysis of outcomes over the first 7 days of treatment showed that the VMS frequency “consistently decreased from days 1 to 6, with the strongest decrease during [the] first 3 days,” while VMS severity “continuously decreased” over days 2 and 3, followed by a further reduction on day 6.
The researchers said there were “similar” reports of treatment-emergent adverse events (TEAEs) in the fezolinetant and placebo arms (65.0 vs 61.1%); the most common TEAEs reported for fezolinetant were COVID-19 (13.3%), headache (8.8%), and fatigue (5.8%). The incidence of serious TEAEs was “low” throughout the study, affecting 4.4% of fezolinetant-treated women and 3.5% of controls.
“There were no safety signals of concern, including liver safety, apparent for the fezolinetant 45-mg dose,” Cano et al added.
The authors concluded that fezolinetant was “well tolerated for moderate-to-severe VMS in women considered unsuitable for HRT,” and that the agent demonstrated “a rapid onset of action and sustained efficacy.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
European Congress of Endocrinology 2024; Stockholm, Sweden: 11–14 May