Clinical data | |
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Trade names | Veozah, Veoza |
Other names | ESN-364 |
AHFS/ Drugs.com | Monograph |
MedlinePlus | a623051 |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Protein binding | 51% [6][ unreliable medical source?] |
Metabolism | CYP1A2, ( CYP2C9, CYP2C19 to lesser extent) [3] |
Metabolites | ES259564 [7] |
Elimination half-life | 9.6h [3] |
Excretion | Urine 76.9%, feces 14.7% [8][ unreliable medical source?] |
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Chemical and physical data | |
Formula | C16H15FN6OS |
Molar mass | 358.40 g·mol−1 |
3D model ( JSmol) | |
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Fezolinetant, sold under the brand name Veozah among others, is a medication used for the treatment of hot flashes (vasomotor symptoms) due to menopause. [3] [9] It is a small-molecule, orally active, selective neurokinin-3 (NK3) receptor antagonist which is under development by for the treatment of sex hormone-related disorders.[ medical citation needed] It is taken by mouth. [3] It is developed by Astellas Pharma which acquired it from Ogeda (formerly Euroscreen) in April 2017. [10] [11] [12]
The most common side effects include abdominal pain, diarrhea, insomnia, back pain, hot flush and elevated hepatic transaminases. [9]
Fezolinetant was approved for medical use in the United States in May 2023, [9] and in the European Union in December 2023. [4] [5] Fezolinetant is the first neurokinin 3 (NK3) receptor antagonist approved by the US Food and Drug Administration (FDA) to treat moderate to severe hot flashes from menopause. [9] The FDA considers it to be a first-in-class medication. [13]
Fezolinetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. [3] [4]
In May 2017, fezolinetant had completed phase I and phase IIa clinical trials for hot flashes in postmenopausal females. [12] Phase IIa trials in polycystic ovary syndrome patients are ongoing. [12]
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. [14] [15]
Fezolinetant shows high affinity for and potent inhibition of the NK3 receptor in vitro (Ki = 25 nM, IC50 = 20 nM). [11] 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. [11] 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. [16] 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. [17] 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. [16] [17]
Unlike GnRH modulators, but similarly to estrogens, NK3 receptor antagonists including fezolinetant and MLE-4901 (also known as AZD-4901, formerly AZD-2624) have been found to alleviate hot flashes in menopausal females. [18] [19] This would seem to be independent of their actions on the hypothalamic–pituitary–gonadal axis and hence on sex hormone production. [18] [19] NK3 receptor antagonists are anticipated as a useful clinical alternative to estrogens for management of hot flashes, but with potentially reduced risks and side effects. [18] [19]
The effectiveness of Veozah to treat moderate to severe hot flashes was demonstrated in each of the first 12-week, randomized, placebo-controlled, double-blind portions of two phase III clinical trials. [9] In both trials, after the first 12 weeks, the females on placebo were then re-randomized to Veozah for a 40-week extension study to evaluate safety. [9] Each trial ran a total of 52 weeks. [9] The average age of the trial participants was 54 years old. [9]
The FDA granted the application for fezolinetant priority review designation. [9] The approval of Veozah was granted to Astellas Pharma US, Inc. [9]
In October 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Veoza, intended for the treatment of hot flushes (vasomotor symptoms) associated with menopause. [4] The applicant for this medicinal product is Astellas Pharma Europe B.V. [4]
Fezolinetant was approved for medical use in the United States in May 2023, [9] and in the European Union in December 2023. [4] [5]
Fezolinetant is the international nonproprietary name. [20]
Fezolinetant is sold under the brand names Veozah and Veoza. [3] [4]