Fezolinetant reduces hot flashes during menopause

The neurokinin-3 receptor antagonist fezolinetant reduced the frequency and severity of menopause-associated vasomotor symptoms (VMS), according to results of the extension arm of the phase III Skylight 2 trial presented at ENDO 2022.

Study participants were 501 women aged ≥40 to 65 years who were experiencing moderate-to-severe VMS associated with menopause (average ≥7 hot flashes/day). They were randomized to receive fezolinetant (30 or 45 mg) or placebo once/day for 12 weeks. The 484 women who completed this treatment period were enrolled in the extension study, where those initially randomized to fezolinetant remained on their respective doses for another 40 weeks, while those initially receiving placebo were re-randomized to receive fezolinetant 30 or 45 mg (placebo/fezolinetant group).

Previous results of the 12-week treatment period showed significant improvements in VMS frequency and severity with fezolinetant over placebo.

VMS frequency reduced between baseline and week 12 with both doses of fezolinetant compared with placebo (least squares [LS] mean difference, -6.83 and -7.50 VMS/day with fezolinetant 30 and 45 mg, respectively, vs placebo). VMS frequency was further reduced between baseline and week 52 (LS mean difference, -8.03 and -8.48 VMS/day, respectively). [ENDO 2022, abstract OR06]

At week 12, VMS severity was reduced with fezolinetant 30 and 45 mg compared with placebo (LS mean difference, -0.64 and -0.77, respectively) and further reduced by week 52 (LS mean difference, -0.83 and -0.95, respectively).

“Women re-randomized from placebo to fezolinetant experienced a reduction in frequency and severity of VMS consistent with that in women receiving fezolinetant throughout the study,” said study author Professor Genevieve Neal-Perry from the University of North Carolina School of Medicine in Chapel Hill, North Carolina, US.

Sleep disturbance, as per PROMIS* total score, was also reduced with fezolinetant 30 and 45 mg compared with placebo at 12 weeks (LS mean difference, -4.1 and -5.5, respectively, with a significant difference between fezolinetant 45 mg and placebo) and 52 weeks (LS mean difference, -6.3 and -5.7, respectively).

The safety assessment showed comparable outcomes at 52 weeks compared with the initial 12-week placebo-controlled period. “No safety signals of concern were apparent for either fezolinetant dose,” the authors said.

“VMS associated with menopause, which are characterized by hot flashes and/or night sweats, affect millions of women worldwide and can impact daily activities and quality of life,” remarked Neal-Perry.

“Fezolinetant 30 mg and 45 mg once daily were efficacious for treatment of moderate-to-severe VMS associated with menopause. Efficacy was persistent and reductions in VMS frequency were maintained during the extension period, at levels consistent with weeks 1 through 12,” said Neal-Perry and co-authors.

The improvements in sleep with fezolinetant 45 mg noted at week 12 were maintained through the extension period, they added.

“These results, along with other fezolinetant studies, will be important in understanding the use of this oral non-hormonal selective [neurokinin-3] receptor antagonist to treat moderate-to-severe VMS associated with menopause,” concluded Neal-Perry.