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]
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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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| 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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| Formula | C16H15FN6OS |
| Molar mass | 358.40 g·mol−1 |
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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]
Medical uses
Fezolinetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.[3][4]
Adverse effects
In September 2024, the US FDA added a warning to the prescribing label that fezolinetant can cause rare but serious liver injury.[14]
History
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.[15][16]
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.[17] 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.[18] 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.[17][18]
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.[19][20] This would seem to be independent of their actions on the hypothalamic–pituitary–gonadal axis and hence on sex hormone production.[19][20] 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.[19][20]
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]
Society and culture
Legal status
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]
Brand names
Fezolinetant is the international nonproprietary name.[21]
Fezolinetant is sold under the brand names Veozah and Veoza.[3][4]
References
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