In the SKYLIGHT1 trial, the nonhormonal agent fezolinetant reduced moderate-to-severe vasomotor symptoms associated with menopause, researchers report. “The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect,” the authors write. “Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation.”
At 97 facilities across the U.S., Canada, Czech Republic, Hungary, Poland, Spain, and the U.K., women aged 40–65 years with an average of 7 or more moderate-to-severe hot flashes per day were randomly assigned to once-daily placebo (n = 175), fezolinetant 30 mg (n = 173), or fezolinetant 45 mg (n = 174). Coprimary endpoints were the mean changes in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12.
“23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal,” the investigators write. “Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean –1.87 [SE 0.42; P <0.001], –2.07 [SE 0.42; P <0.001]) and week 12 (–2.39 [SE 0.44; P <0.001], –2.55 [SE 0.43; P <0.001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (–0.15 [0.06; P = 0.012], –0.19 [0.06; P = 0.002]) and week 12 (–0.24 [0.08; P = 0.002], –0.20 [0.08; P = 0.007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n = 1; fezolinetant 30 mg n = 2; fezolinetant 45 mg n = 0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation.”