Fezolinetant associated with reduced hot flash frequency vs. other nonhormone therapies

Key takeaways:

• Fezolinetant reduced vasomotor symptom frequency more than paroxetine, desvenlafaxine and gabapentin ER.
• Tibolone significantly reduced vasomotor severity vs. fezolinetant, but it is not available in the U.S.

Fezolinetant 45 mg once daily was statistically significantly more effective in reducing moderate to severe vasomotor symptom frequency compared with other nonhormonal — but not hormone-based — therapies in the U.S., researchers reported.

Fezolinetant (Veozah, Astellas) is a nonhormone neurokinin 3 receptor antagonist that was FDA approved in May for treatment of moderate to severe vasomotor symptoms due to menopause.

“In two phase 3 randomized, double-blind trials, SKYLIGHT-1 and SKYLIGHT-2, fezolinetant 45 mg daily significantly reduced the frequency and severity of moderate to severe vasomotor symptoms due to menopause compared with placebo at 4 and 12 weeks,” Antonia Morga, PhD, senior director of global health economics and outcomes research, and health technology assessment strategy lead at Astellas Pharma Europe, and colleagues wrote. “No head-to-head studies directly compared fezolinetant with available HT and non-HT options for vasomotor symptoms to help inform decision-making and treatment selection.”

Morga and colleagues conducted a systematic review and meta-analysis, published in Menopause. They searched multiple databases for phase 3 or 4 randomized controlled trials of postmenopausal women with seven or more moderate to severe vasomotor symptoms daily or 50 or more vasomotor symptoms weekly. Overall, for the network meta-analysis, researchers identified data from all pooled phase 3 fezolinetant trials and 23 comparator publications with 27 HT regimens. Researchers evaluated the mean change in frequency and severity of moderate to severe vasomotor symptoms from baseline to 12 weeks and the proportion of women with 75% or higher reduction in vasomotor symptom frequency at 12 weeks.

Vasomotor frequency changes did not significantly differ between fezolinetant 45 mg and any of the HT regimens studied. Fezolinetant 45 mg was significantly associated with fewer moderate to severe vasomotor symptom events per day compared with the following nonhormonal therapies:

• paroxetine 7.5 mg (mean difference, 1.66; 95% credible interval [CrI], 0.63-2.71);
• desvenlafaxine 50 mg (mean difference, 1.12; 95% CrI, 0.1-2.13) to 200 mg (mean difference, 2.16; 95% CrI, 0.9-3.4); and
• gabapentin extended-release (ER) 1,800 mg (mean difference, 1.63; 95% CrI, 0.48-2.81).

In addition, tibolone 2.5 mg — the only HT regimen evaluable for vasomotor symptom severity — significantly reduced severity compared with fezolinetant 45 mg. For 75% or higher responder rates, fezolinetant 45 mg was less effective compared with tibolone 2.5 mg. Also, conjugated estrogens 0.625 mg/bazedoxifene 20 mg did not differ significantly from other non-HT regimens and was superior to desvenlafaxine 50 mg and placebo. However, tibolone is not available in the U.S. and conjugated estrogens/bazedoxifene is available only as 0.45 mg/20 mg doses in the U.S.

Fezolinetant 45 mg significantly reduced vasomotor symptom severity compared with desvenlafaxine 50 mg and placebo. This reduction did not differ significantly from higher doses of desvenlafaxine or gabapentin ER 1,800 mg.

“Based on indirect comparisons in the [network meta-analysis], fezolinetant 45 mg once daily was significantly more effective in reducing the frequency of moderate to severe vasomotor symptoms than available non-HT options,” the researchers wrote. “For reduction in vasomotor symptoms severity, fezolinetant 45 mg was significantly more effective than desvenlafaxine 50 mg, but not higher doses of desvenlafaxine or gabapentin ER 1,800 mg.”