Neal-Perry, et al published results of a RCT evaluating the “Safety of Fezolinetant
for Vasomotor Symptoms Associated With Menopause” over 52 weeks (Obstetrics
& Gynecology ():10.1097/AOG.0000000000005114, March 9,
2023. | DOI: 10.1097/AOG.0000000000005114) . A total of 1,830 participants
were randomized and took one or more medication dose (July 2019–January 2022).
Treatment-emergent adverse events occurred in 64.1% (391/610) of the placebo
group, 67.9% (415/611) of the fezolinetant 30-mg group, and 63.9% (389/609) of
the fezolinetant 45-mg group. Treatment-emergent adverse events leading to
discontinuation were similar across groups (placebo, 26/610 [4.3%]; fezolinetant 30
mg, 34/611 [5.6%]; fezolinetant 45 mg, 28/609 [4.6%]). Endometrial safety was
assessed in 599 participants. In the fezolinetant 45-mg group, 1 of 203 participants
had endometrial hyperplasia (0.5%; upper limit of one-sided 95% CI 2.3%); there
were no cases in the placebo (0/186) or fezolinetant 30 mg (0/210) group.
Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group
(0.5%; 95% CI 2.2%) with no cases in the other groups. Liver enzyme elevations
more than three times the upper limit of normal occurred in 6 of 583 placebo, 8 of
590 fezolinetant 30 mg, and 12 of 589 fezolinetant 45 mg participants; no Hy’s law
cases were reported (ie, no severe drug-induced liver injury with alanine
aminotransferase or aspartate aminotransferase more than three times the upper
limit of normal and total bilirubin more than two times the upper limit of normal,
with no elevation of alkaline phosphatase and no other reason to explain the
combination). Changes in BMD and trabecular bone score were similar across
groups. The authors concluded that this phase 3 study confirm the 52-week safety
and tolerability of fezolinetant and support its continued development.