Fezolinetant eases symptoms in menopausal women unfit for hormone therapy

Use of fezolinetant demonstrates efficacy and good tolerability in the treatment of moderate-to-severe vasomotor symptoms associated with menopause in women who are deemed unsuitable for hormone therapy, reports a study.

“The findings of this study support the utility of fezolinetant as an effective nonhormonal treatment option for individuals who cannot or choose not to use hormone therapy for the management of moderate-to-severe vasomotor symptoms associated with menopause,” the researchers said. 

This phase IIIb randomized controlled trial was conducted in 16 countries, involving 453 women with moderate-to-severe vasomotor symptoms (mean age 54.5 years, 96.7 percent White).

Eligible participants, who were considered unsuitable candidates for hormone therapy (contraindicated, caution [based on medical history], stoppers [previous discontinuation], or averse [informed choice not to use hormone therapy]), were randomly allocated to receive either fezolinetant 45 mg (n=227) or placebo (n=226) daily for 24 weeks.

Of the participants, 370 (81.7 percent) completed the study (fezolinetant arm: n=195; placebo arm: n=175). Some 452 participants who received at least one dose of the study drug were included in the safety and full analysis sets. Majority of the women were categorized as either hormone therapy averse (37.2 percent) or caution (36.5 percent). [BMJ 2024;387:e079525]

At week 24, women in the fezolinetant arm experienced significant reductions in the frequency (least square mean difference [LSMD], –1.93, 95 percent confidence interval [CI], –2.64 to –1.22; p<0.001) and severity of vasomotor symptoms (LSMD, –0.39, 95 percent CI, –0.57 to –0.21; p<0.001).

Fezolinetant-treated participants also had better sleep quality (via Patient-Reported Outcome Measurement Information System Sleep Disturbance Short Form [PROMIS SD-SF] 8b total score) than those treated with placebo (LSMD, –2.5, 95 percent CI, –3.9 to –1.1; p<0.001). These improvements were seen as early as the first week of treatment.

Safety profile

The incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups (65.0 percent in the treatment group vs 61.1 percent in the placebo group), as was the incidence of serious TEAEs (4.4 percent vs 3.5 percent). The most common TEAEs in the fezolinetant arm were COVID-19 (13.3 percent), headache (8.8 percent), and fatigue (5.8 percent).

“Improvements in frequency of moderate-severe vasomotor symptoms in the fezolinetant group compared with placebo were observed as early as day 1, consistent with efficacy results in phase III studies SKYLIGHT 1 and SKYLIGHT 2,” the researchers said. [J Clin Endocrinol Metab 2023;108:1981-1997; Lancet 2023;401:1091-1102]

“The available safety data appeared generally consistent with the known safety profile for fezolinetant, including data from phase III placebo-controlled trials showing that fezolinetant is well tolerated for as much as 52 weeks,” they added. [Obstet Gynecol 2023;141:737-747]

The current study was limited to participants from 16 Western countries, most of whom were White. Future studies of fezolinetant should consider including global populations with diverse ethnicity or races, according to the researchers.

Vasomotor symptoms, such as hot flushes and night sweats, are the most common and bothersome symptoms in menopausal women, with up to 80 percent experiencing the said conditions. [Am J Public Health 2006;96:1226-1235; Climacteric 2008;11:32-43]