Fezolinetant cuts hot flashes for almost 6 months

Fezolinetant 45 mg appears to be effective  for up to 24 weeks in the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause  in women who are considered unsuitable for hormone therapy. And the response to treatment is strong from day 1.

The drug is currently FDA approved for up to 12 weeks of such treatment.

The study was presented May 11, 2024 at the European Congress of Endocrinology in Stockholm..

“Fezolinetant was effective and well tolerated for 24 weeks and the effect was observed as early as day 1 of treatment. While there are other NK antagonists, none have shown a similar concurrence of efficacy and safety in clinical studies with a sufficiently high number of participants,” said investigator Dr. Antonio Cano of the INCLIVA Research Institute in Valencia, Spain. Caon is also Senior Professor of Obstetrics and Gynecology at the University of Valencia.

DAYLIGHT was a phase 3b, randomised, double-blind, 24-week placebo-controlled study. The investigators enrolled subjects aged ≥40 to ≤65 years with moderate-to-severe VMS who were unsuitable for hormone therapy due to contraindications, caution (prior medical history), stoppers (lack of efficacy, side effects, or medical advice), or averse feeling (chose not to take hormone therapy after discussion with clinician).

The investigators randomised the subjects to placebo or fezolinetant 45 mg once daily.

They enrolled 453 subjects (placebo n=226; fezolinetant n=227), including HT contraindicated (51), caution (165), stoppers (69), and averse feeling (168).

The primary endpoint was mean change in daily VMS frequency of moderate-to-severe episodes from baseline to week 24.

During the first week, subjects treated with fezolinetant achieved a significantly  greater reduction in the daily mean change in frequency of moderate-to-severe VMS compared with placebo (p<0.001). The greatest decrease was during the first 3 days of fezolinetant treatment.

For the endpoint, improvements in frequency and severity of VMS at day 7 were sustained through week 24.

There were no new safety signals for use of  fezolinetant 45mg  through week 24.

The authors concluded, “DAYLIGHT is the first study of fezolinetant to investigate efficacy versus placebo over 24 weeks. Fezolinetant 45 mg was efficacious and well tolerated for moderate-to-severe VMS in women considered unsuitable for HT. An effect on VMS frequency was seen as early as day 1 and maintained through the 24-week placebo-controlled period, demonstrating a rapid onset of action and sustained efficacy with fezolinetant treatment.”