ACOG article 2.1

Treatment with fezolinetant significantly reduced the frequency and severity of vasomotor symptoms (VMS), particularly hot flashes, in women during their menopausal phase, according to the SKYLIGHT 1* trial presented at ACOG 2022.

This double-blind, placebo-controlled, phase III trial involved 522 menopausal women (mean age 54.4 years) with moderate-to-severe VMS of ≥7 hot flashes/day. Participants were randomized to receive fezolinetant 30 mg (n=174) or 45 mg (n=173) once/day or placebo (n=175) for 12 weeks. VMS data were assessed by using the participants’ e-diaries, indicating the number of daily hot flash episodes. [ACOG 2022, abstract A132]

At weeks 4 and 12, patients who received fezolinetant 30 mg had a significant reduction from baseline in daily mean VMS frequency than those who received placebo (least squares [LS] mean difference, -1.87 and -2.39, respectively; p<0.001 for both time points).

Similarly, those on fezolinetant 40 mg achieved a significantly reduced daily mean VMS frequency than those on placebo between baseline and weeks 4 and 12 (LS mean difference, -2.07 and -2.55, respectively; p<0.001 for both time points).

Patients on either dose of fezolinetant also achieved a statistically significant reduction in daily mean VMS severity vs those on placebo between baseline and week 4 (LS mean difference, -0.15; p=0.012 [30 mg] and -0.19; p=0.002 [45 mg]) and week 12 (LS mean difference, -0.24; p=0.002 [30 mg] and -0.20; p=0.007 [45 mg]).

The researchers highlighted that statistically significant reductions in VMS frequency and severity were seen as early as week 1 and were maintained through week 12 for both fezolinetant doses.

Similar rates of treatment-emergent adverse events (TEAEs) were observed between the fezolinetant 30 and 40 mg groups and the placebo groups (37.4 percent, 43.4 percent, and 44.6 percent, respectively). Headache was the most common AE reported across all treatment groups (5.2 percent, 6.4 percent, and 7.4 percent in the fezolinetant 30 mg, fezolinetant 40 mg, and placebo groups, respectively).

“Fezolinetant 30 and 45 mg once daily were efficacious for the treatment of moderate-to-severe VMS associated with menopause, … [with] significant improvements through week 12, observed as early as week 1,” the researchers noted.

“No safety signals of concern were apparent for either dose [of fezolinetant],” they added.