Fezolinetant, sold under the brand name Veozah, among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for the treatment of

hot flash Hot flushes 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 t ...

es (vasomotor symptoms) due to

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

. It is a

small-molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; t ...

, selective neurokinin-3 (NK₃)

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. It was developed by

Astellas Pharma is a Japanese multinational pharmaceutical company, formed on 1 April 2005 from the merger of and . Astellas is a member of the Mitsubishi UFJ Financial Group (MUFJ) keiretsu. History Early foundations Fujisawa Shoten was started in 1894 ...

, which acquired it from Ogeda (formerly Euroscreen) in April 2017. The most common side effects of fezolinetant include abdominal pain, diarrhea,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, 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 The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are Geography of the European Union, located primarily in Europe. The u ...

in December 2023. Fezolinetant is the first NK₃ receptor antagonist approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) to treat moderate to severe hot flashes from menopause. The FDA considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

Fezolinetant is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

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

Adverse effects

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

History

In May 2017, fezolinetant had completed phase I and phase IIa

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s for

es in

postmenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

females. Phase IIa trials in

polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...

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 ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...

. Fezolinetant shows high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for and potent

inhibition Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransm ...

of the NK₃ receptor ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' (K_i = 25 nM, = 20 nM).

Loss-of-function mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis ...

s in ''TACR'' and ''TACR3'', the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s respectively encoding

neurokinin B Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in fe ...

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 Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

(LH)

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

, though not that of

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH), and consequently to dose-dependently decrease

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

and

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

levels in females and

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

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 Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

production Production may refer to: Economics and business * Production (economics) * Production, the act of manufacturing goods * Production, in the outline of industrial organization, the act of making products (goods and services) * Production as a stat ...

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 Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

-like

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s such as loss of

bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to opti ...

. Unlike GnRH modulators, but similarly to

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

s, 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. This would seem to be independent of their actions on the

hypothalamic–pituitary–gonadal axis The hypothalamic–pituitary–gonadal axis (HPG axis, also known as the hypothalamic–pituitary–ovarian/testicular axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single en ...

and hence on sex hormone production. 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. 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. 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. Each trial ran a total of 52 weeks. The average age of the trial participants was 54 years old. The FDA granted the application for fezolinetant

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

designation. The approval of Veozah was granted to Astellas Pharma US, Inc.

Society and culture

Legal status

In October 2023, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

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. The applicant for this medicinal product is Astellas Pharma Europe B.V. Fezolinetant was approved for medical use in the United States in May 2023, and in the European Union in December 2023.

Brand names

Fezolinetant is the international nonproprietary name. Fezolinetant is sold under the brand names Veozah and Veoza.

References

{{Authority control Antigonadotropins 4-Fluorophenyl compounds NK3 receptor antagonists Thiadiazoles Triazolopyrazines N-benzoylpiperazines