Clinical evaluation of the NK3 receptor antagonist fezolinetant (a.k.a. ESN364) for the treatment of menopausal hot flashes

Abstract

Context: NK3 receptor (“NK3”; TACR3) signaling is implicated in the etiology of hot flashes by the clinical pharmacology of neurokinin B (NKB) [ [1] Jayasena C.N. et al. Sci Rep. 2015; 5https://doi.org/10.1038/srep08466 Crossref PubMed Scopus (85) Google Scholar ], neuroanatomical evidence for hypertrophy of NKB-expressing neurons in menopausal women [ [2] Rance N.E. Peptides. 2009; 30: 111-122https://doi.org/10.106/j.peptides.2008.05.016 Crossref PubMed Scopus (0) Google Scholar ], and association between risk of vasomotor symptoms and genetic variation in TACR3 [ [3] Crandall C.J. et al. Menopause. 2016; https://doi.org/10.1097/GME.0000000000000763 Crossref Scopus (43) Google Scholar ]. Fezolinetant is an NK3 antagonist demonstrated to safely modulate hormone biomarkers in premenopausal women [ [4] Fraser G.L. et al. J Clin Endocrinol Metab. 2016; https://doi.org/10.1210/jc.2015-3621 Crossref Scopus (54) Google Scholar ]. Here, we present clinical trial results for fezolinetant in the treatment of menopausal hot flashes (“HF”).