A profile of safety and efficacy of fezolinetant for the treatment of menopausal vasomotor symptoms

Fezolinetant is a first-in-class non-hormonal pharmacological treatment recently approved for moderate-to-severe vasomotor symptoms (VMS) associated with menopause. Its mechanism of action selectively targets the pathophysiology of VMS at hypothalamic level, antagonizing binding of neurokinin B, overexpressed in estrogen deprived menopausal women, to the neurokinin 3 receptor (NK3R) in the thermoregulatory center. Fezolinetant reduced VMS frequency and severity in phase 3 randomized placebo-controlled trials in healthy menopausal women (SKYLIGHT 1 and 2) and in women unsuitable for menopause hormone therapy (MHT) (DAYLIGHT). The effect on VMS positively translated into improvements in menopause-specific quality of life, as well as sleep disturbances and impairment. Safety data were reassuring across studies, especially 52-weeks safety trials (SKYLIGHT 4 and MOONLIGHT 3). Fezolinetant represents a highly anticipated innovation, offering the possibility to bridge the therapeutic gap for many women who cannot or do not wish to use MHT. While the potential application of fezolinetant in some clinical settings will add substantial value to the management of VMS, some research gaps need to be addressed in order to provide meaningful insight into the benefit-risk profile that ultimately will improve counseling and prescription tailoring in symptomatic menopausal women.