Fezolinetant users report improved menopause-related symptoms, quality of life

Key takeaways:

• Fezolinetant 30 mg and 45 mg led to higher vasomotor symptom frequency reductions vs. placebo.
• Fezolinetant also improved measures including vasomotor symptom frequency and menopause-specific quality of life.

Fezolinetant was associated with significant improvements in patient-reported vasomotor symptom frequency and menopause-specific quality of life, according to an analysis published in Menopause.

SKYLIGHT 1 and 2 were phase 3, randomized, double-blind, placebo-controlled studies that evaluated the efficacy of fezolinetant (Veozah, Astellas) in reducing moderate to severe vasomotor symptoms associated with menopause.

“The four coprimary endpoints were met, with data demonstrating that fezolinetant 30 [mg] and 45 mg provided statistically significant improvements in mean daily vasomotor symptom frequency and severity at weeks 4 and 12 compared with placebo,” Rossella E. Nappi, MD, PhD, professor of obstetrics and gynecology, chief of the Research Center for Reproductive Medicine and director of the Gynecological Endocrinology and Menopause Unit, IRCCS San Matteo Foundation, University of Pavia, Italy, and colleagues wrote. “An additional 52-week randomized phase 3 trial, SKYLIGHT 4, confirmed the safety and tolerability of fezolinetant.”

Nappi and colleagues evaluated pooled data from 1,022 women (mean age, 54.3 years) aged at least 40 years from SKYLIGHT 1 and 2 who received at least one fezolinetant dose. Responders were defined as women who experienced vasomotor symptom frequency reductions of at least 50%, 75%, 90% or 100% from baseline to 4 and 12 weeks. Researchers analyzed patient-reported outcome measures, including the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance-Short Form 8b (PROMIS SD-SF-8b) total score, Menopause-Specific Quality of Life (MENQOL) total score and MENQOL vasomotor symptom domain score, to assess clinically meaningful within-patient changes at 4 and 12 weeks compared with baseline.

Researchers assessed single responders, which was the percentage of women who achieved clinically meaningful responses in either vasomotor symptom frequency or one of the patient-reported outcomes, and assessed double and triple responder analyses combining vasomotor symptom frequency plus one or more patient-reported outcome.

In single responder analyses, more women who received fezolinetant 30 mg or 45 mg had at least 50% (47.5% and 53.4% vs. 27.2%), at least 75% (29.2% and 29.9% vs. 13.7%), at least 90% (11.8% and 15.8% vs. 5.8%) and 100% (4.7% and 7.3% vs. 2.3%) reductions in vasomotor symptom frequency at 4 weeks compared with placebo, respectively. Results were similar at 12 weeks, with more women who received fezolinetant 30 mg or 45 mg achieving at least 50% (47.5% and 58.7% vs. 36%), at least 75% (31.9% and 37% vs. 17%), at least 90% (17.4% and 23.2% vs. 9.4%) and 100% (8% and 12.6% vs. 4.4%) reduction in frequency compared with placebo, respectively.

Fezolinetant continued to demonstrate reductions in vasomotor symptom frequency in double and triple responder analyses for vasomotor symptom frequency plus PROMIS SD-SF-8b total score, vasomotor symptom frequency plus MENQOL total score and vasomotor symptom frequency plus MENQOL vasomotor symptom domain score, according to the researchers.

“The data provide further evidence of the utility of fezolinetant as a nonhormone treatment option for women experiencing vasomotor symptoms due to menopause,” the researchers wrote. “Increased emphasis on the clinically meaningful benefit experienced by women with treatment can facilitate meaningful dialogue between clinicians and patients.”