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![]() Above: molecular structure of fezolinetant Below: 3D representation of a fezolinetant molecule | |
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% [8] [ unreliable medical source? ] |
Metabolism | CYP1A2, (CYP2C9, CYP2C19 to lesser extent) [5] |
Metabolites | ES259564 [9] |
Elimination half-life | 9.6h [5] |
Excretion | Urine 76.9%, feces 14.7% [10] [ 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. [5] [11] It is a small-molecule, selective neurokinin-3 (NK3) receptor antagonist taken by mouth. [5] It was developed by Astellas Pharma, which acquired it from Ogeda (formerly Euroscreen) in April 2017. [12] [13] [14]
The most common side effects of fezolinetant include abdominal pain, diarrhea, insomnia, back pain, hot flush, and elevated hepatic transaminases. [11]
Fezolinetant was approved for medical use in the United States in May 2023, [11] and it was approved in the European Union in December 2023. [6] [7] 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. [11] The FDA considers it to be a first-in-class medication. [15]
Fezolinetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. [5] [6]
In September 2024, the US FDA added a warning to the prescribing label that fezolinetant can cause rare but serious liver injury. [16]
In May 2017, fezolinetant had completed phase I and phase IIa clinical trials for hot flashes in postmenopausal females. [14] Phase IIa trials in polycystic ovary syndrome patients are ongoing. [14]
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. [17] [18]
Fezolinetant shows high affinity for and potent inhibition of the NK3 receptor in vitro (Ki = 25 nM, IC50 = 20 nM). [13] 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. [13] 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. [19] 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. [20] 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. [19] [20]
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. [21] [22] This would seem to be independent of their actions on the hypothalamic–pituitary–gonadal axis and hence on sex hormone production. [21] [22] 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. [21] [22]
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. [11] 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. [11] Each trial ran a total of 52 weeks. [11] The average age of the trial participants was 54 years old. [11]
The FDA granted the application for fezolinetant priority review designation. [11] The approval of Veozah was granted to Astellas Pharma US, Inc. [11]
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. [6] The applicant for this medicinal product is Astellas Pharma Europe B.V. [6]
Fezolinetant was approved for medical use in the United States in May 2023, [11] and in the European Union in December 2023. [6] [7]
Fezolinetant is the international nonproprietary name. [23]
Fezolinetant is sold under the brand names Veozah and Veoza. [5] [6]