Fezolinetant

Fezolinetant, sold under the brand name Veozah, among others, is a medication used for the treatment of hot flashes (vasomotor symptoms) due to menopause. It is a small-molecule, selective neurokinin-3 (NK₃) receptor antagonist taken by mouth. It was developed by Astellas Pharma, which acquired it from Ogeda (formerly Euroscreen) in April 2017.

The most common side effects of fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flush, and elevated hepatic transaminases.

Fezolinetant was approved for medical use in the United States in May 2023, and it was approved in the European Union in December 2023. Fezolinetant is the first NK₃ receptor antagonist approved by the US Food and Drug Administration (FDA) to treat moderate to severe hot flashes from menopause. The FDA considers it to be a first-in-class medication.

Fezolinetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.

In September 2024, the US FDA added a warning to the prescribing label that fezolinetant can cause rare but serious liver injury.

In May 2017, fezolinetant had completed phase I and phase IIa clinical trials for hot flashes in postmenopausal females. Phase IIa trials in polycystic ovary syndrome patients are ongoing.

In March 2023, results from SKYLIGHT 1, a Phase III clinical study of the treatment of moderate to severe hot flashes due to menopause, were published in The Lancet.

Fezolinetant shows high affinity for and potent inhibition of the NK₃ receptor in vitro (K_i = 25 nM, IC₅₀Tooltip half-maximal inhibitory concentration = 20 nM). Loss-of-function mutations in TACR and TACR3, the genes respectively encoding neurokinin B and its receptor, the NK₃ receptor, have been found in patients with idiopathic hypogonadotropic hypogonadism. In accordance, NK₃ receptor antagonists like fezolinetant have been found to dose-dependently suppress luteinizing hormone (LH) secretion, though not that of follicle-stimulating hormone (FSH), and consequently to dose-dependently decrease estradiol and progesterone levels in females and testosterone levels in males. As such, they are similar to GnRH modulators, and present as a potential clinical alternative to them for use in the same kinds of indications. However, the inhibition of sex hormone production by NK₃ receptor inactivation tends to be less complete and "non-castrating" relative to that of GnRH modulators, and so they may have a reduced incidence of menopausal-like side effects such as loss of bone mineral density.