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May 06, 2022
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Phase 3 study shows efficacy of fezolinetant in treating menopausal vasomotor symptoms

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SAN DIEGO — Compared with placebo, fezolinetant was efficacious in the treatment of menopause-related vasomotor symptoms with no safety concerns, according to phase 3 data presented at the ACOG Annual Clinical & Scientific Meeting.

The findings confirm those of previous phase 3 trials, which demonstrated the efficacy of the investigational selective neurokinin 3 receptor antagonist in treating moderate to severe vasomotor symptoms (VMS) and its long-term safety.

Data derived from Neal-Perry G, et al. Abstract 132. Presented at: ACOG Annual Clinical & Scientific Meeting; May 6-8, 2022; San Diego.
Data derived from Neal-Perry G, et al. Abstract 132. Presented at: ACOG Annual Clinical & Scientific Meeting; May 6-8, 2022; San Diego.

“VMS are the most common and most bothersome menopause symptoms and when severe, can significantly reduce quality of life and cognitive function,” Genevieve Neal-Perry, MD, PhD, Robert A. Ross Distinguished Professor and chair of the department of OB/GYN at the University of North Carolina at Chapel Hill, told Healio. “Although hormone therapy is effective for managing VMS associated with menopause, it is not an option for some women, leaving a need for nonhormonal therapeutic options.”

Neal-Perry and colleagues randomly assigned 527 women aged 40 to 65 years who had moderate to severe menopause-related VMS to once daily placebo (n = 175), fezolinetant 30 mg (n = 173) or fezolinetant 45 mg (n = 174). They assessed symptom frequency and severity at baseline, 4 weeks and 12 weeks, as well as overall treatment-emergent adverse events.

Compared with placebo, fezolinetant 30 mg significantly reduced VMS frequency, with least squares mean reductions of –1.87 (standard error, 0.42; P < .001) at 4 weeks and –2.39 (standard error, 0.44; P < .001) at 12 weeks. Fezolinetant 45 mg also significantly reduced VMS frequency compared with placebo, with least squares mean reductions of –2.07 (standard error, 0.42; P < .001) at 4 weeks and –2.55 (standard error, 0.43; P < .001) at 12 weeks.

Both dose amounts of fezolinetant reduced symptom severity compared with placebo. At 4 weeks, the mean change was –0.15 (standard error, 0.06; P = .012) for 30 mg and –0.19 (standard error, 0.06; P = .002) for 45 mg. At 12 weeks, the mean change was –0.24 (standard error, 0.08; P = .002) for 30 mg and –0.2 (standard error, 0.08; P = .007) for 45 mg.

Adverse events were reported by 37.4% of women on fezolinetant 30 mg, 43.4% of those on fezolinetant 45 mg and 44.6% of those on placebo, with headache being the most common in 5.2%, 6.4% and 7.4%, respectively.

Genevieve Neal-Perry, MD, PhD
Genevieve Neal-Perry

Neal-Perry suggested that future studies examine the comparative efficacy of fezolinetant and common nonhormonal therapies in women with hormone-responsive cancer and thrombophilia.

“Women with [these diagnoses] have limited treatment options for VMS,” she said. “Moreover, these treatment options are not as effective as estradiol and may have a side effect profile that is intolerable.”