Fezolinetant eases vasomotor symptoms, improves quality of life

Treatment with oral fezolinetant leads to a reduction in vasomotor symptoms (VMS) with large parallel improvements in quality of life, according to data from the phase IIb VESTA trial.

In the 12-week trial, 352 postmenopausal women with VMS were randomly assigned to the following treatment groups: fezolinetant 15 mg (n=45), 30 mg (n=43), 60 mg (n=45), and 90 mg (n=45) twice daily (BID); or 30 mg (n=43), 60 mg (n=45), and 120 mg (n=44) once daily (QD); or placebo (n=43). At baseline, the women were aged 40–65 years and had body mass index of 18–38 kg/m². They reported having ≥50 moderate-to-severe VMS per week.

Compared with placebo, all fezolinetant doses were associated with marked reductions in VMS frequency at weeks 4 (mean, −1.9 to −3.5) and 12 (mean, −1.8 to −2.6; p<0.05). Likewise, severity decreased by a mean of 0.4 to 1.0 with all doses (p<0.05) at week 4 and by 0.2 to 0.6 with the 60-mg and 90-mg BID and 60-mg QD (p<0.05) at week 12.

VMS frequency reductions were accompanied by clinically meaningful changes in patient-reported outcomes. For instance, all doses of fezolinetant improved scores on the Hot Flash-Related Daily Interference Scale at weeks 4 (placebo: −2.2; fezolinetant: range, −2.5 to −3.8) and 12 (placebo: −2.9; fezolinetant: range, −3.3 to −4.3), as well as on the Menopause-Specific Quality of Life questionnaire (week 4, placebo: −1.8; fezolinetant: range, −1.9 to −3.6; week 12, placebo: −2.3; fezolinetant: range, −2.9 to −4.4).

Also, Greene Climacteric Scale-VMS domain scores improved for most fezolinetant doses at both time points (week 4, placebo: −1.7; fezolinetant: range, −2.1 to −3.3; week 12, placebo: −2.1; fezolinetant: range, −2.7 to −3.6).

Treatment-emergent adverse events were mostly mild or moderate, occurring similarly across all fezolinetant groups.

The findings suggest that the neurokinin 3 receptor antagonist fezolinetant, a nonhormonal therapy, may be an attractive treatment option in women with moderate-to-severe VMS associated with menopause, which could translate into meaningful improvements in quality of life, according to the researchers.