Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for

metastatic Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

castration-resistant prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surr ...

(mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth. Common side effects include tiredness,

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, headache,

joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

, high blood pressure, swelling,

low blood potassium Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnor ...

high blood sugar Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

hot flash Hot flashes (also known as 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 ...

es,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

, and

cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three ph ...

. Other severe side effects may include liver failure and

adrenocortical insufficiency The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...

. In males whose partners can become pregnant, birth control is recommended. Supplied as abiraterone acetate it is converted in the body to abiraterone. Abiraterone acetate works by suppressing the production of androgens – specifically it inhibits CYP17A1 – and thereby decreases the

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 stati ...

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

. In doing so, it prevents the effects of these

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

s in prostate cancer. Abiraterone acetate was described in 1995, and approved for medical use in the United States and the European Union in 2011. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is available as a generic medication.

Medical uses

Prostate cancer

Abiraterone acetate is used in combination with

prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...

, a corticosteroid, as a treatment for mCRPC (previously called hormone-resistant or hormone-refractory prostate cancer). This is a form of prostate cancer that is not responding to first-line

androgen deprivation therapy Androgen deprivation therapy (ADT), also called androgen suppression therapy, is an antihormone therapy whose main use is in treating prostate cancer. Prostate cancer cells usually require androgen hormones, such as testosterone, to grow. ADT red ...

or treatment with androgen receptor antagonists. Abiraterone acetate has received

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 respon ...

(FDA) (28 April 2011), European Medicines Agency (EMA) (23 September 2011), Medicines and Healthcare products Regulatory Agency (MHRA) (5 September 2011) and

Therapeutic Goods Administration The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, p ...

(TGA) (1 March 2012) approval for this indication. In Australia it is covered by the

Pharmaceutical Benefits Scheme The Pharmaceutical Benefits Scheme (PBS) is a program of the Australian Government that subsidises prescription medication for Australian citizens and permanent residents, as well as international visitors covered by a reciprocal health care ag ...

when being used to treat castration-resistant prostate cancer and given in combination with

prednisolone Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthr ...

(subject to the conditions that the patient is not currently receiving chemotherapy, is either resistant or intolerant of

docetaxel Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell ...

, has a WHO performance status of <2, and his disease has not since become progressive since treatment with PBS-subsidised abiraterone acetate has commenced). Abiraterone acetate may be useful for prevention of the

flare at the initiation of

GnRH agonist A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treat ...

therapy in men with prostate cancer. In people previously treated with docetaxel survival is increased by 3.9 months (14.8 months versus 10.9 months for placebo). In people with castration-refractory prostate cancer but who had not received chemotherapy those who received abiraterone acetate had a

progression-free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is p ...

of 16.5 months rather than 8.3 months with placebo. After a median follow-up period of 22.2 months, overall survival was better with abiraterone acetate. Dramatic improvement due to new drug combinations was discovered in late 2021. In non-metastatic high risk patients, Zytiga with ADT has recently been shown to increase survival rates by 40+%, and decrease metastasis by 47%.

Contraindications

Contraindications include hypersensitivity to abiraterone acetate. Although documents state that it should not be taken by women who are or who may become pregnant, there is no medical reason that any woman should take it. Women who are pregnant should not even touch the pills unless they are wearing gloves. Other cautions include severe baseline hepatic impairment,

mineralocorticoid excess Hyperaldosteronism is a medical condition wherein too much aldosterone is produced by the adrenal glands, which can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis). This cause of mi ...

, cardiovascular disease including heart failure and hypertension, uncorrected

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

, and adrenocorticoid insufficiency.

Side effects

Side effects by frequency: Very common (>10% frequency): *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

Hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...

* Hypertension *

Diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

Peripheral edema Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent ede ...

Common (1-10% frequency): * Hypertriglyceridaemia *

Sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

Cardiac failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

Angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstru ...

* Arrhythmia * Atrial fibrillation *

Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

Dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

(indigestion) *

Rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...

Alanine aminotransferase Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first character ...

increased *

Aspartate aminotransferase Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme () that was first described by Arthur ...

increased * Fractures *

Hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...

Uncommon (0.1-1% frequency): * Adrenal insufficiency * Myopathy * Rhabdomyolysis Rare (<0.1% frequency): * Allergic alveolitis

Overdose

Experience with overdose of abiraterone acetate is limited. There is no specific

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

for abiraterone acetate overdose, and treatment should consist of general supportive measures, including monitoring of cardiac and liver function.

Interactions

Abiraterone acetate is a CYP3A4 substrate and hence should not be administered concurrently with strong CYP3A4 inhibitors such as ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital. It also inhibits

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

, and CYP3A4 and likewise should not be taken concurrently with substrates of any of these enzymes that have a narrow therapeutic index.

Spironolactone Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...

generally exerts anti-androgenic effects, but experimental evidence exists that it acts as an androgen receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation. This is supported by the observations described in several case reports.

Pharmacology

Pharmacodynamics

Antiandrogenic activity

Abiraterone, the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

of abiraterone acetate, inhibits

CYP17A1 Cytochrome P450 17A1 (steroid 17α-monooxygenase, 17α-hydroxylase, 17-alpha-hydroxylase, 17,20-lyase, 17,20-desmolase) is an enzyme of the hydroxylase type that in humans is encoded by the ''CYP17A1'' gene on chromosome 10. It is ubiquitously exp ...

, which manifests as two enzymes, 17α-hydroxylase ( = 2.5 nM) and 17,20-lyase ( = 15 nM) (approximately 6-fold more selective for inhibition of 17α-hydroxylase over 17,20-lyase) that are expressed in testicular, adrenal, and prostatic tumor tissues. CYP17A1 catalyzes two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by its 17α-hydroxylase activity, and (b) the subsequent formation of

dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It fun ...

(DHEA) and androstenedione, respectively, by its 17,20-lyase activity. DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17A1 activity by abiraterone acetate thus decreases circulating levels of androgens such as DHEA,

, and

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includ ...

(DHT). Abiraterone acetate, via abiraterone, has the capacity to lower circulating testosterone levels to less than 1 ng/dL (i.e., undetectable) when added to castration. These concentrations are considerably lower than those achieved by castration alone (~20 ng/dL). The addition of abiraterone acetate to castration was found to reduce levels of DHT by 85%, DHEA by 97 to 98%, and androstenedione by 77 to 78% relative to castration alone. In accordance with its antiandrogenic action, abiraterone acetate decreases the weights of the

prostate gland The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physio ...

seminal vesicles The seminal vesicles (also called vesicular glands, or seminal glands) are a pair of two convoluted tubular glands that lie behind the urinary bladder of some male mammals. They secrete fluid that partly composes the semen. The vesicles are 5� ...

, and

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...

. Abiraterone also acts as a partial antagonist of the androgen receptor (AR), and as an inhibitor of the enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD), CYP11B1 (steroid 11β-hydroxylase), CYP21A2 (Steroid 21-hydroxylase), and other

CYP450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

s (e.g.,

, and CYP3A4). In addition to abiraterone itself, part of the activity of the drug has been found to be due to a more potent

, δ⁴-abiraterone (D4A), which is formed from abiraterone by 3β-HSD. D4A is an inhibitor of CYP17A1, 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase, and 5α-reductase, and has also been found to act as a competitive antagonist of the AR reportedly comparable to the potent antagonist

enzalutamide Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castrat ...

. However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and promotes prostate cancer progression. Its formation can be blocked by the coadministration of

dutasteride Dutasteride, sold under the brand name Avodart among others, is a medication primarily used to treat the symptoms of a benign prostatic hyperplasia (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefi ...

, a potent and selective

5α-reductase inhibitor 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...

Estrogenic activity

There has been interest in the use of abiraterone acetate for the treatment of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

due to its ability to lower

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

levels. However, abiraterone has been found to act as a direct agonist of the

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

, and induces proliferation of human breast cancer cells ''

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

''. If abiraterone acetate is used in the treatment of breast cancer, it should be combined with an estrogen receptor antagonist like

fulvestrant Fulvestrant, sold under the brand name Faslodex among others, is a medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced br ...

. In spite of its antiandrogenic and estrogenic properties, abiraterone acetate does not appear to produce

gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse ( ...

as a side effect.

Other activities

Due to inhibition of

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...

biosynthesis, abiraterone acetate can cause glucocorticoid deficiency,

, and associated

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

s. This is why the medication is combined with

, a corticosteroid, which serves as a means of glucocorticoid replacement and prevents mineralocorticoid excess. Abiraterone acetate, along with galeterone, has been identified as an inhibitor of

sulfotransferase Sulfotransferases (SULTs) are transferase enzymes that catalyze the transfer of a sulfo group from a donor molecule to an acceptor alcohol or amine. The most common sulfo group donor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In the case o ...

s (

SULT2A1 Bile salt sulfotransferase also known as hydroxysteroid sulfotransferase (HST) or sulfotransferase 2A1 (ST2A1) is an enzyme that in humans is encoded by the ''SULT2A1'' gene. Function Sulfotransferase enzymes catalyze the sulfate conjugation ...

, SULT2B1b,

SULT1E1 Estrogen sulfotransferase is an enzyme that in humans is encoded by the ''SULT1E1'' gene. Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are ...

), which are involved in the

sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

of DHEA and other endogenous steroids and compounds, with K_i values in the sub-micromolar range.

Pharmacokinetics

After oral administration, abiraterone acetate, the prodrug form in the commercial preparation, is converted into the active form, abiraterone. This conversion is likely to be esterase-mediated and not CYP-mediated. Administration with food increases absorption of the drug and thus has the potential to result in increased and highly variable exposures; the drug should be consumed on an empty stomach at least one hour before or two hours after food. The drug is highly

protein bound Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

(>99%), and is metabolised in the liver by CYP3A4 and

to inactive metabolites. The drug is excreted in feces (~88%) and urine (~5%), and has a terminal half-life of 12 ± 5 hours.

Chemistry

Abiraterone acetate, also known as 17-(3-pyridinyl)androsta-5,16-dien-3β-ol acetate, is a synthetic

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...

steroid and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

androstadienol Androstadienol, or androsta-5,16-dien-3β-ol, is a 16-androstene class endogenous steroid, pheromone, and chemical intermediate to several other pheromones that is found in the sweat of both men and women. Androstadienol and androstadienone ...

(androsta-5,16-dien-3β-ol), an endogenous androstane

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

. It is specifically a derivative of androstadienol with a

pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...

ring Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...

attached at the C17 position and an acetate

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

attached to the C3β hydroxyl group. Abiraterone acetate is the C3β acetate ester of abiraterone.

History

In the early 1990s, Mike Jarman, Elaine Barrie, and Gerry Potter of the

Cancer Research UK Cancer Research UK (CRUK) is the world's largest independent cancer research organization. It is registered as a charity in the United Kingdom and Isle of Man, and was formed on 4 February 2002 by the merger of The Cancer Research Campaign and t ...

Centre for Cancer Therapeutics in the Institute of Cancer Research in

London London is the capital and List of urban areas in the United Kingdom, largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary dow ...

set out to develop drug treatments for prostate cancer. With the

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mo ...

androgen synthesis inhibitor ketoconazole as a model, they developed abiraterone acetate, filing a patent in 1993 and publishing the first paper describing it the following year. Rights for commercialization of the drug were assigned to BTG, a UK-based specialist healthcare company. BTG then licensed the product to Cougar Biotechnology, which began development of the commercial product. In 2009, Cougar was acquired by Johnson & Johnson, which developed and sells the commercial product, and is conducting ongoing

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

s to expand its clinical uses. Abiraterone acetate was approved by the United States

on 28 April 2011 for mCRPC. The FDA press release made reference to a phase III

in which abiraterone acetate use was associated with a median survival of 14.8 months versus 10.9 months with placebo; the study was stopped early because of the successful outcome. Abiraterone acetate was also licensed by the European Medicines Agency. Until May 2012 the

National Institute for Health and Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...

(NICE) did not recommend use of the drug within the NHS on cost-effectiveness grounds. This position was reversed when the manufacturer submitted revised costs. The use is currently limited to men who have already received one docetaxel-containing chemotherapy regimen. It was subsequently approved for the treatment of mCSPC in 2018.

Society and culture

Names

''Abiraterone'' is the and of abiraterone acetate's major active metabolite abiraterone. ''Abiraterone acetate'' is the , , and of abiraterone acetate. It is also known by its developmental code names ''CB-7630'' and ''JNJ-212082'', while ''CB-7598'' was the developmental code name of abiraterone. Abiraterone acetate is marketed by

Janssen Biotech Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American c ...

(a subsidiary of Johnson & Johnson) under the brand name Zytiga, and by

Sun Pharmaceutical Sun Pharmaceutical Industries Limited (d/b/a Sun Pharma) is an Indian multinational pharmaceutical company headquartered in Mumbai, that manufactures and sells pharmaceutical formulations and active pharmaceutical ingredients (APIs) in more th ...

under the brand name Yonsa. Generic versions of abiraterone acetate have been approved in the United States. Generic versions of Yonsa are not available . In May 2019, the

United States Court of Appeals for the Federal Circuit The United States Court of Appeals for the Federal Circuit (in case citations, Fed. Cir. or C.A.F.C.) is a United States court of appeals that has special appellate jurisdiction over certain types of specialized cases in the U.S. federal court ...

upheld a Patent Trial and Appeal Board decision invalidating a patent by Johnson & Johnson on abiraterone acetate. Intas Pharmaceuticals markets the drug under the brand name Abiratas, Cadila Pharmaceuticals markets the drug as Abretone, and

Glenmark Pharmaceuticals Glenmark Pharmaceuticals Limited is an Indian multinational pharmaceutical company headquartered in Mumbai, India. History it was founded in 1977 by Gracias Saldanha as a generic drug and active pharmaceutical ingredient manufacturer; he na ...

as Abirapro. It is marketed as Yonsa by Sun Pharmaceutical Industries (licensed from Churchill Pharmaceuticals).

Available forms

Abiraterone acetate is available as tablets. Abiraterone acetate is marketed widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere in Europe, Australia, New Zealand, Latin America, Asia, and Israel.

Economics

A generic version is available in India at a price of $238 a month . The National Centre for Pharmacoeconomics initially found abiraterone acetate to not be cost effective based on prices in 2012, however following an agreement to supply at a lower price it was accepted in 2014. A generic Zytiga version is available in India at a price of under $230 a month as of 2020.

Research

Abiraterone acetate is under development for the treatment of

and

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...

and as of March 2018, is in phase II clinical trials for these indications. It was also under investigation for the treatment of

congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cort ...

, but no further development has been reported for this potential use.

References

External links

* {{Portal bar , Medicine 11β-Hydroxylase inhibitors 3β-Hydroxysteroid dehydrogenase inhibitors 5α-Reductase inhibitors Acetate esters Androstanes Antiestrogens Antiglucocorticoids Conjugated dienes CYP2D6 inhibitors CYP17A1 inhibitors Hormonal antineoplastic drugs Johnson & Johnson brands Prodrugs Prostate cancer 3-Pyridyl compounds Steroid sulfotransferase inhibitors Steroidal antiandrogens Synthetic estrogens World Health Organization essential medicines Wikipedia medicine articles ready to translate