Fezolinetant may reduce VMS frequency, improve QoL in postmenopausal women

Postmenopausal women with moderate or severe vasomotor symptoms (VMS), such as hot flashes and/or night sweats, who received fezolinetant were more likely to experience reduced VMS frequency and better health-related quality of life (QoL) than those on placebo, according to the secondary analysis of VESTA* study.

“Consistent with the reported efficacy of fezolinetant to reduce the frequency and severity of VMS, … [this study] reflects notable improvements in [patient-reported outcome (PRO)] measure domains that have a strong association with VMS, including the MENQoL** vasomotor function domain, HFRDIS** total score, and GCS^** VMS score,” said the researchers.

This double-blind, dose-ranging, parallel-group study evaluated 352 healthy postmenopausal women (mean age 54.6 years) with moderate or severe VMS (≥50 episodes/week). Participants were randomized to receive either fezolinetant 15, 30, 60, or 90 mg BID or 30, 60, or 120 mg QD or placebo for 12 weeks. All participants recorded the number of daily VMS episodes in an e-diary. MENQoL questionnaire, and HFRDIS and GCS scores were used to assess PROs from baseline to week 12 with decreasing values indicating improvement. [Menopause 2020;27:1350-1356]

At the last on-treatment week (defined as the last 7 days of treatment), more women treated with fezolinetant 15, 30, 60, or 90 mg BID achieved a ≥90 percent reduction in the frequency of VMS from baseline than those treated with placebo (51.2, 51.2, 61.9, and 81.6 percent, respectively vs 39.0 percent).

Similarly, more women on fezolinetant 30, 60, or 120 mg QD experienced a ≥90 percent reduction in VMS frequency than those on placebo (53.8, 54.8, and 54.5 percent, respectively vs 39.0 percent).

At week 12, a numerically greater reduction in overall mean MENQoL score was observed across all fezolinetant dose groups vs the placebo group (least squares [LS] mean difference, -0.2, -0.5, -0.4, and -0.4 for 15, 30, 60, or 90 mg BID and -0.1, 0.1, and -0.3 for 30, 60, or 120 mg QD).

The fezolinetant group also demonstrated a greater reduction in MENQoL score for vasomotor function domain than the placebo group at week 12 (LS mean change from baseline, -3.2, -3.5, -3.8, and -4.4 for 15, 30, 60, or 90 mg BID and -2.9, -3.3, and -3.6 for 30, 60, or 120 mg QD vs -2.3). This was particularly noticeable with the higher doses in the fezolinetant BID and QD dosing groups, said the researchers.

Fezolinetant recipients also demonstrated a greater decrease in mean HFRDIS score at week 12 than placebo recipients (LS mean change from baseline, -3.6, -3.8, -4.3, and -4.2 for 15, 30, 60, or 90 mg BID and -3.3, -3.5, and -3.9 for 30, 60, or 120 mg QD vs -2.9) which exceeded the minimally important difference (MID, -1.76).

The GCS VMS score was also numerically greater in both fezolinetant BID and QD dosing groups at week 12 than the placebo group (-2.7, -3.1, -3.6, and -3.6 for 15, 30, 60, or 90 mg BID and -2.9, -2.8, and -2.9 for 30, 60, or 120 mg QD vs -2.1).

Adverse event (AE) rates were similar across treatment groups, with no incidence of major dose-related AEs that could potentially affect the PROs, the researchers noted.

“[Overall,] across all fezolinetant groups, … [majority] of the participants experienced a reduction in moderate or severe VMS, … [and] these reductions … were accompanied by improvements in PROs … [that] were maintained throughout the 12-week treatment period,” said the researchers.

“The clear trend for numerically greater improvement in the fezolinetant treatment group relative to the placebo group, coupled with the magnitude with which fezolinetant treatment groups exceeded the previously published [clinically important difference] or MID thresholds relative to placebo, suggest a potential benefit of therapy that should be evaluated further in larger trials,” they added.

*VESTA: A dose-ranging study of the efficacy of ESN364 in postmenopausal women suffering vasomotor symptoms (hot flashes)

**MENQoL: Menopause-Specific Quality of Life; HFRDIS: Hot Flash-Related Daily Interference Scale; GCS: Greene Climacteric Scale