Investigational Drug Fezolinetant Safe, Effective For Reducing Hot Flashes

The investigational drug fezolinetant can reduce moderate to severe menopausal vasomotor symptoms (VMS) and is well tolerated, according to a new clinical trial.

"Fezolinetant as a novel, nonhormone, centrally acting drug may provide an option for women who desire treatment for VMS but have contraindications to or concerns regarding the use of hormone products," Dr. Graeme L. Fraser of Astellas Pharma SA in Brussels, Belgium, and colleagues write in Menopause.

The drug is a neurokinin-3 receptor (NK3R) antagonist, targeting neurons in the hypothalamus that express kisspeptin, neurokinin B and dynorphin (KNDy neurons). Changes in these neurons that occur as estrogen levels decline may contribute to the hypersensitivity to heat stimuli that is thought to cause menopausal VMS, Dr. Fraser and colleagues note.

Astellas launched phase-3 trials of fezolinetant in August 2019. The current report is from a phase-2b trial that tested seven dosing regimens in 352 patients, 287 of whom finished the study.

At week 4, patients on fezolinetant reported 1.9 to 3.5 fewer VMS per day, and 1.8 to 2.6 fewer VMS per day at week 12, significantly more than placebo.

Mean differences in VMS severity score from placebo were -0.4 to -1 at week 4 (significant for all dosing regimens) and -0.2 to -0.6 at week 12 (significant for 60 and 90 mg BID and 60 mg QD).

Response, defined as a 50% reduction in frequency of moderate to severe VMS, occurred in 81.4%-94.7% of the fezolinetant groups, versus 58.5% of the placebo group (all doses P < 0.05).

Rates of adverse events were similar for the patients on fezolinetant and those on placebo.

"The current study adds to the growing body of literature describing the neural circuits in the hypothalamus underlying the loss of thermoregulatory control in VMS and further exemplifies the importance of NK3R signaling as a therapeutic target for the nonhormone treatment of hot flashes," the authors write.

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