Daily fezolinetant shows efficacy in treating vasomotor symptoms in menopause

The nonhormonal selective neurokinin-3 receptor antagonist fezolinetant was effective and well tolerated in treating moderate to severe vasomotor symptoms associated with menopause, according to study data.

Researchers reported study results in The Journal of Clinical Endocrinology & Metabolism.

“There is a need for nonhormonal treatment of vasomotor symptoms. This has potential to fill this need,” Kimball A. Johnson, MD, clinical research investigator and medical director of iResearch Atlanta, told Healio. “If approved, fezolinetant will be a first-in-class, nonhormonal medication for moderate to severe vasomotor symptoms that may also help with sleep.”

This multinational, randomized, double-blind, placebo-controlled, multicenter, 12-week phase 3 trial, SKYLIGHT 2, included 500 women aged 40 to 65 years with a minimum average of seven moderate to severe menopausal vasomotor symptoms per day. All participants were randomly assigned to 12 weeks of placebo (n = 167), fezolinetant 30 mg (Astellas Pharma; n = 166) or fezolinetant 45 mg (n = 167). After the 12-week trial, participants were again randomly assigned to fezolinetant 30 mg or 45 mg for an additional 40 weeks.

The primary endpoints were mean daily change from baseline to 4 and 12 weeks in vasomotor symptoms frequency and severity as well as safety.

Both 30 mg and 45 mg fezolinetant statistically significantly reduced the frequency and severity of vasomotor symptoms at weeks 4 and 12 compared with placebo. At week 4, the least squares mean reduction in vasomotor frequency with fezolinetant 30 mg was –1.82 (P < .001) and –2.55 with the 45 mg (P < .001) dose compared with placebo. At week 12, this reduction was –1.86 for 30 mg (P < .001) and –2.53 for 45 mg (P < .001) compared with placebo.

For vasomotor symptom severity, at week 4, reductions were –0.15 for fezolinetant 30 mg (P < .05) and –0.29 for the 45 mg dose (P < .001) compared with placebo. At week 12, these reductions were –0.16 for 30 mg (P < .05) and –0.29 for 45 mg (P < .001) compared with placebo. Vasomotor frequency and severity improvement were observed as early as week 1 and maintained through 52 weeks on either fezolinetant dose, according to researchers.

Researchers also noted that serious treatment-emergent adverse events were infrequent, with two reported by 2% of those who received fezolinetant 30 mg, 1% of those who received fezolinetant 45 mg and 0% among those who received placebo.

“These findings support continued development of fezolinetant as a novel nonhormonal treatment option for vasomotor symptoms associated with menopause,” the researchers wrote.

According to Johnson, more confirmatory studies and studies with a primary endpoint focusing on sleep are needed.