22 May 2023
Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause. Recently, Johnson et al.  published the results of SKYLIGHT 2, a phase 3 double-blind placebo controlled RCT aimed at assessing the efficacy and safety of fezolinetant for the treatment of moderate-to-severe menopause related VMS. Women, age 40-65 years with a minimum mean of 7 moderate-to-severe VMS per day, were randomized to receive 12 weeks once-daily fezolinetant 30 mg, fezolinetant 45 mg or placebo. Those who completed 12 weeks were re-randomized to fezolinetant 30mg or 45 mg for 40 additional weeks. Primary endpoints were mean daily change of frequency and severity of VMS from baseline to W4 and W12. The study reported that both fezolinetant doses significantly reduced moderate-to-severe VMS frequency and severity at W4 and W12 in comparison to placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo was: fezolinetant 30 mg, -1.82 (0.46; p < 0.001); 45 mg, -2.55 (0.46; p < 0.001); W12: 30 mg, -1.86 (0.55; p < 0.001); 45 mg, -2.53 (0.55; p < 0.001). For VMS severity (scale 0-3) results were: W4: 30 mg, -0.15 (0.06; p< 0.05); 45 mg, -0.29 (0.06; p < 0.001); W12: 30 mg, -0.16 (0.08; p <0.05); 45 mg, -0.29 (0.08; p < 0.001). Significant improvement in VMS frequency (30 and 45 mg) and severity (45 mg) was observed by W1 and was maintained through W12. Serious treatment-emergent adverse events were infrequent: 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively; liver function abnormalities were rare and transient. The authors concluded that daily fezolinetant 30 mg and 45 mg were efficacious and well-tolerated for the treatment of moderate-to-severe menopause related VMS.