Fezolinetant a viable nonhormone therapy for menopausal vasomotor symptoms

The selective neurokinin 3 receptor antagonist fezolinetant induces rapid reductions in moderate-to-severe menopausal vasomotor symptoms (VMS) with a tolerable safety profile, according to the results of a phase IIb trial.

A total of 352 women aged 40 to 65 years with moderate-to-severe VMS (≥50 episodes/week) were randomized to receive 12 weeks of treatment with fezolinetant 15, 30, 60 or 90 mg twice daily, or 30, 60 or 120 mg once daily, or placebo. Of these women, 287 completed the trial.

Primary outcomes examined were decreases in VMS frequency and severity (calculated as follows: [number of moderate VMS × 2] + [number of severe VMS × 3]/total daily moderate-to-severe VMS) at weeks 4 and 12. The key secondary outcome was response (≥50-percent reduction in moderate-to-severe VMS frequency).

Compared with placebo, fezolinetant reduced moderate-to-severe VMS frequency by −1.9 to −3.5/day at week 4 and by −1.8 to −2.6/day at week 12 (p<0.05 vs placebo). Mean difference in VMS severity score vs placebo was −0.4 to −1 at week 4 (p<0.05 for all doses) and −0.2 to −0.6 at week 12 (p<0.05 for 60 and 90 mg BID and 60 mg QD).

Response was achieved by 81.4 percent to 94.7 percent of participants with fezolinetant vs 58.5 percent with placebo at the end of treatment (p<0.05 for all doses).

Treatment-emergent adverse events (TEAEs) were mostly mild to moderate, and there were no serious TEAEs documented.