Fezolinetant Proves Effective for Reducing Vasomotor Menopausal Symptoms in Phase 2b Trial

August 7, 2020

Results of the VESTA trial indicate fezolinetant could one day provide a non-hormonal, oral option for reducing vasomotor menopausal symptoms and improving quality of life in postmenopausal women.

Data from a phase 2b study suggests the neurokinin-3 receptor antagonist fezolinetant could prove useful as a non-hormonal treatment for vasomotor menopausal symptoms.

Published in Menopause, results of the VESTA study indicate oral fezolinetant was associated with higher responder rates than placebo and greater improvements in quality of life and other patient-reported outcome measures.

“This is an extraordinarily successful result and offers promise of relief to millions of women," said lead investigator Nanette Santoro, MD, chair of the Department of Obstetrics and Gynecology at the University of Colorado School of Medicine, in a statement. "This study paves the way for further studies of a longer treatment duration and in a larger group of people."

Designed as a 12-week, double-blind, placebo-controlled study, VESTA enrolled 356 women and randomized them to various doses of fezolinetant or placebo. The primary outcomes of interest for the trial was the proportion of patients at each week who experienced at least a 50% decrease in baseline frequency of moderate or severe vasomotor menopausal symptoms, the proportion who experienced at least a 50% reduction from baseline in the frequency of mild, moderate, or severe vasomotor menopausal symptoms, proportion of patients who had absolute reductions from baseline of 2, 3, 4, and 5 in the mean number of moderate or severe vasomotor menopausal symptoms per 24 hours, and the proportion of those who had absolute reductions from baseline of 2, 3, 4, and 5 in the mean number of mild, moderate, or severe vasomotor menopausal symptoms per 24 hours.

Secondary outcomes of interest for the analysis included patient-reported outcome measures, such as Menopause-Specific Quality of Life questionnaire, the Hot Flash-Related Daily Interference Scale, and the Greene Climacteric Scale at baseline and weeks 4, 8, and 12.

For inclusion in the study, patients needed to be healthy postmenopausal women between the ages of 40-65 years experiencing 50 or more moderate to severe vasomotor menopausal symptom episodes per week during a 35-day screening period. In total, 7 fezolinetant dosing regimens were examined in the study—15, 30, 60, or 90 mg twice daily or 30, 60, or 120 mg once daily.

Of the 356 women who underwent randomization, 352 received at least one dose of study drug and were included in the analysis. Those included int he analysis had a mean age of 54.6 years, 73% of participants were white, and approximately one-third of participants reported being a current or former smoker.

Upon analysis, a greater proportion of women receiving fezolinetant met the definitions for response at week 12. When assessing according to mean changes in baseline in Menopause-Specific Quality of Life, investigators noted scores exceed the minimally important differences (1.2) at weeks 4 (placebo: 1.8; fezolinetant: range, 1.9 to 3.6)and 12 (placebo: -2.3; fezolinetant: range, -2.9 to -4.4). When assessing mean changes in Hot Flash-Related Daily Interference Scale, investigators noted differences exceeded the minimally important differences (1.76) at week 4 (placebo: -2.2; fezolinetant: range, -2.5 to -3.8)and week 12 (placebo: -2.9; fezolinetant: range, -3.3 to -4.3). For Green Climacteric Scale, vasomotor menopausal symptoms domain scores improved across most fezolinetant doses versus placebo at week 4 (placebo: -1.7; fezolinetant: range, -2.1 to -3.3) and week 12 (placebo: -2.1; fezolinetant: range, -2.7 to -3.6).

Based on the results of the phase 2b study, investigators concluded oral fezolinetant was associated with increased responder rates and larger quality of life improvements than placebo for reducing vasomotor menopausal symptom-related interference in daily life.

"The occurrence of VMS [vasomotor symptoms] interfere with sleep, concentration, memory, work productivity, and personal relationships and has been linked to feelings of depression, irritability, anxiety, fatigue, and social embarrassment/isolation," study authors wrote. "All of these factors contribute to the observed negative influence of VMS on psychological well-being and health-related quality of life."

This study, titled “Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA),” was published in Menopause.