Clinical data | |
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Trade names | Veozah, Veoza |
Other names | ESN-364 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a623051 |
License data |
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Routes of administration | By mouth |
ATC code | |
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Pharmacokinetic data | |
Protein binding | 51% [4] [ unreliable medical source? ] |
Metabolism | CYP1A2, (CYP2C9, CYP2C19 to lesser extent) [1] |
Metabolites | ES259564 [5] |
Elimination half-life | 9.6h [1] |
Excretion | Urine 76.9%, feces 14.7% [6] [ unreliable medical source? ] |
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CAS Number | |
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ChEBI | |
ChEMBL | |
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. [1] [7] 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. [1] It is developed by Astellas Pharma which acquired it from Ogeda (formerly Euroscreen) in April 2017. [8] [9] [10]
The most common side effects include abdominal pain, diarrhea, insomnia, back pain, hot flush and elevated hepatic transaminases. [7]
Fezolinetant was approved for medical use in the United States in May 2023, [7] and in the European Union in December 2023. [2] [3] 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. [7] The FDA considers it to be a first-in-class medication. [11]
Fezolinetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause. [1] [2]
In May 2017, fezolinetant had completed phase I and phase IIa clinical trials for hot flashes in postmenopausal females. [10] Phase IIa trials in polycystic ovary syndrome patients are ongoing. [10]
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. [12] [13]
Fezolinetant shows high affinity for and potent inhibition of the NK3 receptor in vitro (Ki = 25 nM, IC50 = 20 nM). [9] 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. [9] 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. [14] 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. [15] 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. [14] [15]
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. [16] [17] This would seem to be independent of their actions on the hypothalamic–pituitary–gonadal axis and hence on sex hormone production. [16] [17] 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. [16] [17]
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. [7] 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. [7] Each trial ran a total of 52 weeks. [7] The average age of the trial participants was 54 years old. [7]
The FDA granted the application for fezolinetant priority review designation. [7] The approval of Veozah was granted to Astellas Pharma US, Inc. [7]
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. [2] The applicant for this medicinal product is Astellas Pharma Europe B.V. [2]
Fezolinetant was approved for medical use in the United States in May 2023, [7] and in the European Union in December 2023. [2] [3]
Fezolinetant is the international nonproprietary name. [18]
Fezolinetant is sold under the brand names Veozah and Veoza. [1] [2]
Hot flashes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to 30 minutes for each occurrence.
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.
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Astellas Pharma Inc. is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of Yamanouchi Pharmaceutical Co., Ltd. and Fujisawa Pharmaceutical Co., Ltd.. On February 5, 2020, the company announced management changes effective from April 1, 2020.
Neurokinin 1 (NK1) antagonists (-pitants) are a novel class of medications that possesses unique antidepressant, anxiolytic, and antiemetic properties. NK-1 antagonists boost the efficacy of 5-HT3 antagonists to prevent nausea and vomiting. The discovery of neurokinin 1 (NK1) receptor antagonists was a turning point in the prevention of nausea and vomiting associated with cancer chemotherapy.
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Osanetant (developmental code name SR-142,801) is a neurokinin 3 receptor antagonist which was developed by Sanofi-Synthélabo and was being researched for the treatment of schizophrenia but was discontinued. It was the first non-peptide NK3 antagonist developed in the mid-1990s.
Esmirtazapine (ORG-50,081) is a tetracyclic antidepressant drug that was under development by Organon for the treatment of insomnia and vasomotor symptoms (e.g., hot flashes) associated with menopause. Esmirtazapine is the (S)-(+)-enantiomer of mirtazapine and possesses similar overall pharmacology, including inverse agonist actions at H1 and 5-HT2 receptors and antagonist actions at α2-adrenergic receptors.
Bionovo was an American biotechnology company focused on the discovery and development of botanically derived treatments for women's health and cancer based in Emeryville, California. The company had multiple drug candidates in U.S. Food and Drug Administration (FDA) clinical trials- Menerba a selective estrogen receptor beta agonist for hot flashes associated with menopause Seala a selective estrogen receptor beta agonist for menopausal vaginal dryness and Bezielle for advanced breast cancer. The company has ceased activity after filing for Chapter 7 bankruptcy protection in California. Bionovo's stock is no longer listed.
Menerba, also known as Menopause Formula 101 (MF-101), is a botanical drug candidate that acts as a selective estrogen receptor modulator (SERM) which is being studied for its potential to relieve hot flashes associated with menopause. Menerba, an estrogen receptor beta (ERβ) agonist (ERBA), is part of a new class of receptor subtype-selective estrogens, which is selective in transcriptional regulation to one of the two known estrogen receptor (ER) subtypes. Menerba consists of 22 herbs that have been used historically in traditional Chinese medicine.
Ospemifene is an oral medication indicated for the treatment of dyspareunia – pain during sexual intercourse – encountered by some women, more often in those who are post-menopausal. Ospemifene is a selective estrogen receptor modulator (SERM) acting similarly to an estrogen on the vaginal epithelium, building vaginal wall thickness which in turn reduces the pain associated with dyspareunia. Dyspareunia is most commonly caused by "vulvar and vaginal atrophy."
A botanical drug is defined in the United States Federal Food, Drug, and Cosmetic Act as a botanical product that is marketed as diagnosing, mitigating, treating, or curing a disease; a botanical product in turn, is a finished, labeled product that contains ingredients from plants. Chemicals that are purified from plants, like paclitaxel, and highly purified products of industrial fermentation, like biopharmaceuticals, are not considered to be botanical products.
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Pavinetant (INN, USAN; developmental code names MLE-4901, AZD-4901, AZ-12472520, AZD-2624), is a small-molecule, orally active, selective neurokinin-3 (NK3) receptor antagonist which was under development by AstraZeneca and Millendo Therapeutics for the treatment of hot flashes and polycystic ovary syndrome (PCOS). It was also under investigation for the treatment of schizophrenia, but development was discontinued for this indication due to lack of effectiveness. In November 2017, development of the medication for hot flashes and PCOS was also terminated after its developer assessed the clinical risks and benefits.
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Waljit Dhillo is an endocrinologist and a Professor of Endocrinology & Metabolism at the Imperial College London. He is the Director of Research at the Division of Medicine & Integrated Care at Imperial College Healthcare NHS Trust and the Dean of the National Institute for Health and Care Research (NIHR) Academy. His research focuses on how the endocrine system controls body weight and reproductive functions.
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