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Abiraterone acetate
Clinical data
Pronunciationa" bir a' ter one
Trade namesZytiga, Yonsa, others
Other namesCB-7630; JNJ-212082; 17-(3-Pyridinyl)androsta-5,16-dien-3β-ol acetate, abiraterone (BAN UK), abiraterone acetate (JAN JP), abiraterone acetate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa611046
License data
Pregnancy
category
Routes of
administration		By mouth[2][3]
Drug classAntineoplastic
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown, but may be 50% at most on empty stomach[7]
Protein bindingAbiraterone: ~99.8% (to albumin and α1-AGpTooltip alpha-1 acid glycoprotein)[7][2][8]
MetabolismEsterases, CYP3A4, SULT2A1[8]
MetabolitesAbiraterone, others[2][7]
Elimination half-lifeAbiraterone: 12–24 hours[2][7][3]
ExcretionFeces: 88%[2][8]
Urine: 5%[2][8][3]
Identifiers
  • [(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.149.063 Edit this at Wikidata
Chemical and physical data
FormulaC26H33NO2
Molar mass391.555 g·mol−1
3D model (JSmol)
Melting point144 to 145 °C (291 to 293 °F) [9]
  • CC(=O)O[C@H]1CC[C@@]2([C@H]3CC[C@]4([C@H]([C@@H]3CC=C2C1)CC=C4C5=CN=CC=C5)C)C
  • InChI=1S/C26H33NO2/c1-17(28)29-20-10-12-25(2)19(15-20)6-7-21-23-9-8-22(18-5-4-14-27-16-18)26(23,3)13-11-24(21)25/h4-6,8,14,16,20-21,23-24H,7,9-13,15H2,1-3H3/t20-,21-,23-,24-,25-,26+/m0/s1 checkY
  • Key:UVIQSJCZCSLXRZ-UBUQANBQSA-N checkY
  (verify)

Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer.[10] Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC).[2][3] It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog.[2] It is taken by mouth.[10]

Common side effects include tiredness, vomiting, headache, joint pain, high blood pressure, swelling, low blood potassium, high blood sugar, hot flashes, diarrhea, and cough.[10][2] Other severe side effects may include liver failure and adrenocortical insufficiency.[2] In males whose partners can become pregnant, birth control is recommended.[2] Supplied as abiraterone acetate it is converted in the body to abiraterone.[2] Abiraterone acetate works by suppressing the production of androgens – specifically it inhibits CYP17A1 – and thereby decreases the production of testosterone.[10] In doing so, it prevents the effects of these hormones in prostate cancer.[10]

Abiraterone acetate was described in 1995, and approved for medical use in the United States and the European Union in 2011.[11][2] It is on the World Health Organization's List of Essential Medicines.[12] It is available as a generic medication.[13]

Medical uses

[edit]

Abiraterone acetate is used in combination with prednisone, a corticosteroid, as a treatment for mCRPC (previously called hormone-resistant or hormone-refractory prostate cancer).[2][6][5][4] This is a form of prostate cancer that is not responding to first-line androgen deprivation therapy or treatment with androgen receptor antagonists. Abiraterone acetate has received Food and Drug Administration (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 (TGA) (1 March 2012) approval for this indication.[2][6][5][4] In Australia it is covered by the Pharmaceutical Benefits Scheme when being used to treat castration-resistant prostate cancer and given in combination with prednisone/prednisolone (subject to the conditions that the patient is not currently receiving chemotherapy, is either resistant or intolerant of docetaxel, has a WHO performance status of <2, and his disease has not since become progressive since treatment with PBS-subsidised abiraterone acetate has commenced).[14]

Abiraterone acetate/methylprednisolone, sold under the brand name Yonsa Mpred, is a composite package that contains both abiraterone acetate (Yonsa) and methylprednisolone.[15] It was approved for medical use in Australia in March 2022.[15][16][17]

Contraindications

[edit]

Contraindications include hypersensitivity to abiraterone acetate. Although documents state that it should not be taken by women who are or who may become pregnant,[6][18] 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.[18] Other cautions include severe baseline hepatic impairment, mineralocorticoid excess, cardiovascular disease including heart failure and hypertension, uncorrected hypokalemia, and adrenocorticoid insufficiency.[19]

Side effects

[edit]

Side effects by frequency:[2][6][5][4][19]

Very common (>10% frequency):

Common (1-10% frequency):

Uncommon (0.1-1% frequency):

Rare (<0.1% frequency):

Overdose

[edit]

Experience with overdose of abiraterone acetate is limited.[2] There is no specific antidote for abiraterone acetate overdose, and treatment should consist of general supportive measures, including monitoring of cardiac and liver function.[2]

Interactions

[edit]

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.[19][18] It also inhibits CYP1A2, CYP2C9, and CYP3A4 and likewise should not be taken concurrently with substrates of any of these enzymes that have a narrow therapeutic index.[19][18]

Spironolactone 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.[20] This is supported by the observations described in several case reports.[21]

Pharmacology

[edit]

Pharmacodynamics

[edit]
Abiraterone, the active metabolite of abiraterone acetate.
Steroidogenesis, showing the actions of 17α-hydroxylase and 17,20-lyase in green boxes at left.

Antiandrogenic activity

[edit]

Abiraterone, the active metabolite of abiraterone acetate, inhibits CYP17A1, which manifests as two enzymes, 17α-hydroxylase (IC50Tooltip half-maximal inhibitory concentration = 2.5 nM) and 17,20-lyase (IC50 = 15 nM) (approximately 6-fold more selective for inhibition of 17α-hydroxylase over 17,20-lyase)[22][23] 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 (DHEA) and androstenedione, respectively, by its 17,20-lyase activity.[24] 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, testosterone, and dihydrotestosterone (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.[22][25] These concentrations are considerably lower than those achieved by castration alone (~20 ng/dL).[25] 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.[25] In accordance with its antiandrogenic action, abiraterone acetate decreases the weights of the prostate gland, seminal vesicles, and testes.[26]

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 CYP450s (e.g., CYP1A2, CYP2C9, and CYP3A4).[19][27][28][29] In addition to abiraterone itself, part of the activity of the drug has been found to be due to a more potent active metabolite, δ4-abiraterone (D4A), which is formed from abiraterone by 3β-HSD.[30] D4A is an inhibitor of CYP17A1, 3β-hydroxysteroid dehydrogenase/Δ5-4 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.[30] However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and promotes prostate cancer progression.[31] Its formation can be blocked by the coadministration of dutasteride, a potent and selective 5α-reductase inhibitor.[31]

Estrogenic activity

[edit]

There has been interest in the use of abiraterone acetate for the treatment of breast cancer due to its ability to lower estrogen levels.[32] However, abiraterone has been found to act as a direct agonist of the estrogen receptor, and induces proliferation of human breast cancer cells in vitro.[32] If abiraterone acetate is used in the treatment of breast cancer, it should be combined with an estrogen receptor antagonist like fulvestrant.[32] In spite of its antiandrogenic and estrogenic properties, abiraterone acetate does not appear to produce gynecomastia as a side effect.[33]

Other activities

[edit]

Due to inhibition of glucocorticoid biosynthesis, abiraterone acetate can cause glucocorticoid deficiency, mineralocorticoid excess, and associated adverse effects.[34] This is why the medication is combined with prednisone, a corticosteroid, which serves as a means of glucocorticoid replacement and prevents mineralocorticoid excess.[35]

Abiraterone acetate, along with galeterone, has been identified as an inhibitor of sulfotransferases (SULT2A1, SULT2B1b, SULT1E1), which are involved in the sulfation of DHEA and other endogenous steroids and compounds, with Ki values in the sub-micromolar range.[36]

Pharmacokinetics

[edit]

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 (>99%), and is metabolized in the liver by CYP3A4 and SULT2A1 to inactive metabolites. The drug is excreted in feces (~88%) and urine (~5%), and has a terminal half-life of 12 ± 5 hours.[18]

Chemistry

[edit]
See also: Steroidal antiandrogen and List of steroidal antiandrogens

Abiraterone acetate, also known as 17-(3-pyridinyl)androsta-5,16-dien-3β-ol acetate, is a synthetic androstane steroid and a derivative of androstadienol (androsta-5,16-dien-3β-ol), an endogenous androstane pheromone.[37] It is specifically a derivative of androstadienol with a pyridine ring attached at the C17 position and an acetate ester attached to the C3β hydroxyl group.[37] Abiraterone acetate is the C3β acetate ester of abiraterone.[37]

History

[edit]

In the early 1990s, Mike Jarman, Elaine Barrie, and Gerry Potter of the Cancer Research UK Centre for Cancer Therapeutics in the Institute of Cancer Research in London set out to develop drug treatments for prostate cancer. With the nonsteroidal 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.[11][38] 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.[39] In 2009, Cougar was acquired by Johnson & Johnson, which developed and sells the commercial product, and is conducting ongoing clinical trials to expand its clinical uses.[40]

Abiraterone acetate was approved by the United States Food and Drug Administration on 28 April 2011 for mCRPC.[41][42] The FDA press release made reference to a phase III clinical trial 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.[43] Abiraterone acetate was also licensed by the European Medicines Agency.[44] Until May 2012 the National Institute for Health and Clinical Excellence (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.[45] The use is currently limited to men who have already received one docetaxel-containing chemotherapy regimen.[46][47] It was subsequently approved for the treatment of mCSPC in 2018.[48]

Society and culture

[edit]

Names

[edit]

Abiraterone is the INNTooltip International Nonproprietary Name and BANTooltip British Approved Name of abiraterone acetate's major active metabolite abiraterone.[49][50] Abiraterone acetate is the USANTooltip United States Adopted Name, BANMTooltip British Approved Name Modified, and JANTooltip Japanese Accepted Name of abiraterone acetate.[49] It is also known by its developmental code names CB-7630 and JNJ-212082, while CB-7598 was the developmental code name of abiraterone.[49][51]

Abiraterone acetate is marketed by Janssen Biotech (a subsidiary of Johnson & Johnson) under the brand name Zytiga,[49] and by Sun Pharmaceutical under the brand name Yonsa.[49]

Generic versions of abiraterone acetate have been approved in the United States.[52] Generic versions of Yonsa are not available as of November 2019.[53] In May 2019, the United States Court of Appeals for the Federal Circuit upheld a Patent Trial and Appeal Board decision invalidating a patent by Johnson & Johnson on abiraterone acetate.[54]

Intas Pharmaceuticals markets the drug under the brand name Abiratas, Cadila Pharmaceuticals markets the drug as Abretone, and Glenmark Pharmaceuticals as Abirapro.[citation needed] It is marketed as Yonsa by Sun Pharmaceutical Industries (licensed from Churchill Pharmaceuticals).[55][56]

Brand names

[edit]

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.[49]

Economics

[edit]

A generic version is available in India at a price of $238 a month as of 2019.[57] 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.[57][58] A generic Zytiga version is available in India at a price of under $230 a month as of 2020.[59]

Research

[edit]

Abiraterone acetate is under development for the treatment of breast cancer and ovarian cancer and as of March 2018, is in phase II clinical trials for these indications.[51] It was also under investigation for the treatment of congenital adrenal hyperplasia, but no further development has been reported for this potential use.[51]

Prostate cancer

[edit]

In people previously treated with docetaxel survival is increased by 3.9 months (14.8 months versus 10.9 months for placebo).[60]

In people with castration-refractory prostate cancer but who had not received chemotherapy those who received abiraterone acetate had a progression-free survival 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.[61]

Abiraterone acetate may be useful for prevention of the testosterone flare at the initiation of GnRH agonist therapy in men with prostate cancer.[62]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Abiraterone acetate

View on Grokipedia
from Grokipedia
Abiraterone acetate is an orally bioavailable used primarily to treat advanced , particularly metastatic castration-resistant (mCRPC) and high-risk metastatic castration-sensitive (mCSPC). Sold under the brand name Zytiga, it is administered in combination with a such as or prednisolone to suppress production that fuels tumor growth despite surgical or medical castration. Upon ingestion, abiraterone acetate is rapidly converted to its active form, abiraterone, which potently and irreversibly inhibits the cytochrome P450 17α-hydroxylase/17,20-lyase (), thereby blocking the biosynthesis of androgens like testosterone and in the adrenal glands, testes, and intratumoral sites. The development of abiraterone acetate addressed a critical need in management, where tumors often progress to a castration-resistant state due to alternative sources despite . Preclinical studies demonstrated its ability to reduce levels and inhibit tumor growth in animal models, leading to phase I trials that established a recommended dose of 1000 mg daily. Pivotal phase III clinical trials, including the COU-AA-301 study for post-chemotherapy mCRPC patients, showed significant improvements in overall survival (14.8 months versus 10.9 months with plus ), prompting FDA approval on April 28, 2011, as the first oral synthesis inhibitor for this indication. Subsequent expansions included approval for chemotherapy-naïve mCRPC in 2012 based on the COU-AA-302 trial and for high-risk mCSPC in 2018 following the and trials, which confirmed benefits in radiographic and overall survival when added to . Abiraterone is typically taken as 1000 mg tablets once daily on an empty (at least 1 hour before or 2 hours after ) to optimize absorption, alongside 10 mg daily (for example, 5 mg twice daily) to counteract mineralocorticoid-related adverse effects from CYP17 inhibition, such as and . Common side effects include joint pain or swelling, hot flashes, , fatigue, and , while serious risks involve cardiac arrhythmias, liver function abnormalities, and adrenocortical insufficiency, necessitating regular monitoring of , electrolytes, and liver enzymes. Recent research as of 2025 has explored lower doses (e.g., 500 mg or less) with to improve tolerability and reduce costs without compromising efficacy, as well as combinations with like niraparib for patients with repair mutations, enhancing in mCSPC. Contraindicated in women (especially pregnant or ) and requiring contraception in men due to teratogenic potential, abiraterone remains a cornerstone of endocrine in metastatic , significantly extending survival in targeted populations.

Clinical applications

Indications and efficacy

Abiraterone acetate is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men in combination with prednisone or prednisolone. It is also approved for the treatment of metastatic high-risk castration-sensitive prostate cancer (mCSPC) in combination with androgen deprivation therapy (ADT). A fixed-dose combination of abiraterone acetate with the niraparib (Akeega), taken with , is indicated for adults with BRCA-mutated mCRPC who have not previously received a new hormonal agent for mCRPC. Efficacy in mCRPC was established in the phase 3 COU-AA-301 , which demonstrated that abiraterone acetate plus prolonged median overall survival to 14.8 months compared to 10.9 months with plus in patients post- ( [HR] 0.65; 95% CI 0.54-0.78). In chemotherapy-naïve patients, the COU-AA-302 showed improvements in radiographic (rPFS) and overall survival, supporting its use to delay initiation. For high-risk mCSPC, the phase 3 trial reported that abiraterone acetate plus with ADT reduced the risk of death or progression by 53% (HR 0.47; 95% CI 0.39-0.57) compared to plus ADT, with median overall survival of 53 months versus 36.5 months. The trial similarly showed a 71% reduction in the risk of death at 3 years (HR 0.29; 95% CI 0.25-0.34) when abiraterone acetate plus prednisolone was added to standard-of-care , including ADT, in men with metastatic . Patient selection for abiraterone acetate typically includes men with mCRPC who have shown inadequate response to prior receptor-targeted therapies or such as , or those with high-risk mCSPC defined by criteria like Gleason score ≥8 or visceral metastases. The indication for mCSPC was expanded in 2018 based on the and trials, establishing its role in early intervention to improve survival outcomes.

Dosage and administration

Abiraterone acetate is administered orally in combination with a to manage excess. The standard recommended dose for the Zytiga is 1,000 mg (four 250 mg tablets) once daily, taken with 5 mg orally once daily for metastatic castration-sensitive or 5 mg twice daily for metastatic castration-resistant . For the Yonsa , a micronized version with improved , the dose is 500 mg (four 125 mg tablets) once daily in combination with 4 mg orally twice daily. Tablets should be swallowed whole with a full of . The Zytiga formulation must be taken on an empty , at least 1 hour before or 2 hours after a , to ensure consistent absorption, while Yonsa may be taken with or without food, providing greater flexibility. Patients receiving abiraterone acetate should also be on a analog or have undergone bilateral . Dose adjustments are required for hepatic impairment. In patients with moderate hepatic impairment (Child-Pugh class B), the Zytiga dose should be reduced to 250 mg once daily, and for Yonsa, to 125 mg once daily; treatment should not be initiated in those with severe impairment (Child-Pugh class C). No dose adjustment is necessary for renal impairment. If or severe adverse effects occur, dosing should be interrupted and resumed at a reduced level upon resolution, or discontinued if toxicity persists. Monitoring includes baseline and periodic assessments of (ALT, AST, and ), , and serum levels, particularly during the initial months of therapy and as clinically indicated. Treatment is typically continued until disease progression or unacceptable . The Yonsa micronized , approved in 2018, allows for a lower dose compared to non-micronized versions due to enhanced dissolution and absorption.

Safety and adverse effects

Contraindications

Abiraterone acetate has no absolute contraindications per FDA labeling. However, per EMA guidelines, it is contraindicated in women who are or may become pregnant due to the risk of fetal harm, as demonstrated by showing adverse developmental effects including reduced fetal weight, decreased survival, and alterations in external genitalia such as decreased ano-genital distance. It is also contraindicated in patients with to abiraterone acetate or any of its excipients, given reports of anaphylactic reactions including difficulty , swollen face, or . Additionally, use is contraindicated in patients with severe baseline hepatic impairment (Child-Pugh Class C), as the drug's hepatic increases the risk of in this population. It is contraindicated in combination with radium 223 dichloride due to increased risks of fractures and mortality observed in clinical trials. Warnings and precautions include uncontrolled , severe , and a of QT interval prolongation, as abiraterone acetate can exacerbate these conditions through mineralocorticoid excess leading to fluid retention, , and potential cardiac arrhythmias. Strong CYP3A4 inducers should be avoided or require dose adjustments due to reduced efficacy and altered . The drug is not indicated for use in women, except for female healthcare professionals handling it under appropriate precautions, owing to its mechanism of androgen suppression and lack of clinical data in this population. In pediatric patients, abiraterone acetate is not indicated due to the absence of safety and efficacy data. For elderly patients, while there are no specific contraindications, caution is advised due to higher rates of comorbidities that may amplify risks such as cardiovascular events or hepatic issues. Regarding pregnancy and fertility, abiraterone acetate is teratogenic in animal models at exposures as low as 0.03 times the clinical exposure, causing embryo-fetal toxicity without confirming . Males of reproductive potential must use effective contraception during treatment and for three weeks after the last dose to prevent exposure to partners who could become . Animal studies also indicate potential effects on , including reduced counts, decreased motility, altered morphology, and decreased weights of reproductive organs, suggesting possible impairment of male .

Common and serious side effects

Abiraterone acetate commonly causes side effects in more than 10% of patients, primarily due to mineralocorticoid excess from elevated adrenocorticotropic hormone (ACTH) levels, including fatigue (up to 39% incidence), joint pain (arthralgia, 30%), peripheral edema (25-27%), hypertension (8.5-37%), hypokalemia (17-28%), diarrhea (10-18%), and urinary tract infections (12%). Other frequent effects (>10%) encompass nausea, hot flushes, cough, and headache. Serious side effects include , with grade 3-4 elevations in (ALT) or aspartate aminotransferase (AST) occurring in approximately 6% of patients across five randomized clinical trials, and rare cases of fulminant hepatitis, , or death reported postmarketing. may arise, particularly if co-administration is inadequate, leading to symptoms like and . Cardiac events, including arrhythmias, , and (2.6% incidence versus 0.9% ), are also notable, with QT prolongation and observed postmarketing. Bone fractures occur at higher rates with long-term use, especially alongside glucocorticoids or in contraindicated combinations such as with 223 dichloride (e.g., 28.6% vs. 11.4% in the ERA-223 trial for mCRPC), contributing to risk; monitoring is recommended in mCSPC settings like the trial. Frequency data from pivotal trials highlight these risks: in the COU-AA-301 trial for post-chemotherapy metastatic castration-resistant , hypertension affected 8.5% and 28% of patients (all grades); in the trial for high-risk metastatic castration-sensitive , reached 37% and 20% (all grades). has identified rare allergic reactions, such as allergic alveolitis causing and . Management strategies focus on monitoring and intervention: monthly assessment of , serum , and fluid retention is recommended, with potassium supplementation and antihypertensives used for excess symptoms. (ALT, AST, ) should be performed prior to initiation, every two weeks for the first three months, and monthly thereafter, with dose interruption for grade 3-4 and discontinuation if levels exceed five times the upper limit of normal (ULN) for ALT/AST or three times ULN for . Concomitant (5-10 mg daily) mitigates some and ACTH-related effects but may exacerbate bone loss, necessitating monitoring and consideration of bisphosphonates or for fracture prevention in at-risk patients. For cardiac risks, patients with preexisting conditions require close electrocardiographic surveillance.

Overdose

Human experience with overdose of abiraterone acetate is limited, and there is no specific antidote available. Symptoms of overdose are expected to be an exaggeration of the drug's known adverse effects, potentially including severe hypokalemia, hypertension, elevated liver enzymes, fast or irregular heartbeat, lightheadedness, dizziness, fainting, shortness of breath, muscle weakness, and upper abdominal pain or tenderness. Additional risks may involve cardiac arrhythmias due to electrolyte imbalances or mineralocorticoid excess, and in severe cases, potential for adrenal crisis from disrupted steroidogenesis. Management of abiraterone acetate overdose focuses on supportive care, including immediate discontinuation of the drug, intravenous fluids for hydration, electrolyte correction (particularly potassium supplementation for ), and monitoring for arrhythmias, cardiac failure, and liver function abnormalities. may be administered if ingestion was recent to reduce absorption, but is ineffective due to the drug's high protein binding (>99% to and alpha-1 acid glycoprotein). Patients should be observed for at least 48-72 hours post-overdose to detect delayed complications such as hepatic injury or cardiovascular events. Reported cases of abiraterone acetate overdose are rare and primarily accidental, with post-marketing surveillance indicating mostly transient effects such as liver enzyme elevations that resolve upon discontinuation. For instance, isolated reports describe high-dose ingestions leading to reversible hepatic injury without long-term sequelae when promptly managed. The for abiraterone acetate overdose is generally favorable with early intervention, as effects are typically reversible following drug cessation and supportive . To prevent overdose, abiraterone acetate is administered as a once-daily dose, and on proper storage (at , away from children) and adherence to prescribed regimens is essential.

Drug interactions

Drug-drug interactions

Abiraterone acetate, a substrate of , exhibits pharmacokinetic interactions primarily with modulators of this enzyme. Strong inhibitors such as result in only a modest 15% increase in abiraterone exposure, with no clinically meaningful impact on its . Similarly, , another strong inhibitor, is expected to have minimal effects based on and analogous data, though coadministration should be monitored for potential subtle increases in exposure. In contrast, strong inducers like rifampin significantly decrease abiraterone exposure by 55%, potentially reducing efficacy; such combinations should be avoided, or if unavoidable, the abiraterone dose may be increased to twice daily during coadministration. As a potent inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase), abiraterone acetate alters steroidogenesis, leading to interactions with other agents affecting this pathway. Concomitant use with other strong CYP17 inhibitors should be avoided to prevent excessive suppression of synthesis and heightened risk of excess. Caution is advised with substrates like dexamethasone, which is commonly coadministered to mitigate -related adverse effects; while effective in , preclinical data suggest dexamethasone may slightly reduce abiraterone plasma levels, warranting clinical monitoring for . Specific drug combinations can exacerbate toxicity or compromise therapeutic outcomes. Early case reports suggested potential pharmacodynamic interactions between and abiraterone, including androgenic effects at high doses leading to elevated PSA and shortened PFS. However, a 2024 retrospective study in veterans found no compromise in efficacy or survival with coadministration, with possibly better outcomes. Since was excluded from pivotal trials, monitoring is advised if used concomitantly. Additionally, abiraterone's induction of increases the risk of prolongation, particularly when combined with other QT-prolonging agents such as ; electrolyte monitoring and ECG assessment are recommended in such cases to mitigate cardiac risks. Clinical recommendations emphasize proactive management in settings. Dose adjustments or alternative therapies are preferred for strong inducers, while may guide use with inhibitors or CYP17-related agents. Abiraterone also inhibits and CYP2C8, necessitating caution or dose reductions for substrates like or pioglitazone to prevent . As of 2025, recent developments include warnings in combinations like Akeega (niraparib/abiraterone acetate), a dual-action tablet approved for BRCA-mutated metastatic castration-resistant . No significant pharmacokinetic interaction occurs between niraparib (a ) and abiraterone, but strong inducers remain contraindicated due to reduced abiraterone efficacy, and monitoring for additive effects on and myelosuppression is advised.

Food and other interactions

Abiraterone acetate must be administered on an empty stomach to ensure consistent drug exposure, with no food consumed for at least two hours before and one hour after the dose, as food significantly increases its bioavailability. High-fat meals can elevate the area under the curve (AUC) by up to 10-fold, while low-fat meals increase it approximately fivefold, potentially leading to higher plasma concentrations and increased risk of toxicity. This food effect arises from enhanced absorption in the gastrointestinal tract when taken with meals, necessitating fasting administration to avoid variability in exposure and adverse events. Grapefruit juice should be avoided during treatment with abiraterone acetate, as it acts as a inhibitor and can increase drug levels, mimicking certain drug-drug interactions and raising the risk of . Alcohol consumption may exacerbate associated with abiraterone acetate by adding stress to the liver, potentially worsening liver enzyme elevations and related side effects. Smoking has minimal documented impact on abiraterone acetate metabolism, though it is generally advised to avoid use, as it can intensify overall treatment-related side effects without specific pharmacokinetic alterations. Herbal supplements such as St. John's wort should be avoided, as it induces and may decrease abiraterone acetate concentrations, reducing efficacy. Patients receiving abiraterone acetate require counseling on proper meal timing to optimize absorption and minimize risks, including instructions to avoid over-the-counter supplements or herbals without consulting a healthcare provider to prevent unintended interactions. Due to potential side effects such as or , patients should be advised to refrain from or operating machinery if these symptoms occur, ensuring safety during daily activities. When co-administered with , as is standard, additive gastrointestinal effects may arise, including increased risk of ulcers or irritation, warranting monitoring and possible use of protective agents like inhibitors.

Pharmacology

Pharmacodynamics

Abiraterone acetate is a that undergoes rapid deacetylation to form abiraterone, its . Abiraterone acts as an irreversible inhibitor of the enzyme cytochrome P450 17A1 (), also known as 17α-hydroxylase/17,20-lyase, which catalyzes key steps in . By binding to the of , abiraterone blocks the conversion of and progesterone to dehydroepiandrosterone (DHEA) and , respectively, thereby suppressing production in the testes, adrenal glands, and intratumoral sites within cells. The antiandrogenic effects of abiraterone stem from this inhibition of synthesis, leading to a profound reduction in serum testosterone levels, typically to castrate levels below 1 ng/dL in patients with castration-resistant . This suppression extends to extragonadal production, including intratumoral sources, without direct antagonism of the (AR). Unlike AR antagonists, abiraterone does not bind to or block the AR itself, relying instead on depleting availability to inhibit AR signaling. CYP17A1 inhibition also results in estrogenic activity due to the accumulation of upstream steroid such as and progesterone. These can be shunted toward synthesis via aromatase-mediated pathways, potentially elevating levels and contributing to side effects like hot flashes. Additionally, the blockade promotes excess by increasing levels of deoxycorticosterone () and , which can cause , , and fluid retention; these effects are mitigated by co-administration of low-dose to replace glucocorticoids and suppress (ACTH) drive. Abiraterone demonstrates high affinity for , with an IC50 of approximately 2-4 nM for both the 17α-hydroxylase and 17,20-lyase activities, indicating potent inhibition. It exhibits minimal off-target effects on other enzymes, underscoring its selectivity for pathways.

Pharmacokinetics

Abiraterone acetate, a , is rapidly hydrolyzed by esterases in the intestinal mucosa and liver to its active form, abiraterone, following . The median time to reach maximum plasma concentration (Tmax) of abiraterone is approximately 2 hours (range: 1-3 hours), with steady-state concentrations achieved within 3 days of daily dosing. The absolute oral of abiraterone acetate has not been determined due to the absence of an intravenous , but systemic exposure is low and highly variable under fasted conditions, with a marked effect that can increase abiraterone area under the curve (AUC) by up to 10-fold; therefore, it is recommended to administer on an empty at least 1 hour before or 2 hours after a to minimize variability. Abiraterone exhibits extensive distribution throughout the body, with a mean of approximately 19,669 L following intravenous administration in healthy subjects, indicating wide tissue penetration. It is highly bound to plasma proteins (>99%), primarily to and alpha-1 acid glycoprotein. Abiraterone crosses the blood-brain barrier only minimally, limiting its exposure. Metabolism of abiraterone occurs predominantly in the liver, where it is converted via 3A4 () and sulfotransferase 2A1 (SULT2A1) to inactive metabolites, including abiraterone sulfate and N-oxide abiraterone sulfate, which together account for the majority of circulating metabolites. An , Δ4-abiraterone, is also formed through a minor pathway and contributes approximately 10% to the overall pharmacological activity by inhibiting additional steroidogenic enzymes. The mean terminal of abiraterone is 12 ± 5 hours. Excretion of abiraterone and its metabolites occurs primarily via the fecal route (88% of the dose), with unchanged abiraterone acetate and abiraterone comprising about 55% and 22% of the fecal content, respectively, while only 5% is eliminated in , mostly as metabolites. Following a single oral dose, clearance is consistent with hepatic elimination. In special populations, are altered in hepatic impairment: mild impairment increases abiraterone AUC by 1.1-fold with a of 18 hours, moderate impairment by 3.6-fold with a of 19 hours, and severe impairment by 7-fold overall (with a 2-fold increase in unbound fraction), necessitating dose adjustments or avoidance. No clinically significant changes in abiraterone exposure occur in patients with renal impairment, including end-stage renal disease on dialysis. In elderly patients, abiraterone exposure tends to be higher due to age-related reductions in clearance, though no specific dose adjustment is required.

Chemistry

Chemical structure

Abiraterone acetate has the molecular C26_{26}H33_{33}NO2_{2} and a molecular weight of 391.6 g/mol. It is a white to off-white, non-hygroscopic, crystalline powder that is highly lipophilic, with an (logP) of 5.12, and practically insoluble in water. The pKa of the pyridyl nitrogen is 5.19. Abiraterone acetate features a steroidal scaffold derived from , consisting of an core with a Δ5^{5}- between carbons 5 and 6, an at the 3β-position, and a 17-(3-pyridyl) attached at the 17β-position. The includes 3S,8R,9S,10R,13S,14S configuration, with the hydroxy equivalent at 3β and the at 17β. The pyridyl group at C17 is essential for binding to CYP17 ( 17A1). The acetate ester at C3 functions as a moiety, which undergoes to yield the active form abiraterone (C24_{24}H31_{31}NO). A minor , Δ4^{4}-abiraterone, can form through metabolic of the in the A-ring.

Synthesis

Abiraterone acetate is synthesized primarily from dehydroepiandrosterone (DHEA), a readily available steroidal precursor, through a multi-step process that introduces the characteristic 3-pyridyl at the C-17 position while protecting functional groups to ensure selectivity. The original synthesis, developed in the , proceeds via organometallic addition to the 17-ketone, followed by to form the Δ^{16} essential for the molecule's structure and activity. The process begins with protection of the 3β-hydroxy group in DHEA as the , typically achieved by reaction with in the presence of a base like or , yielding dehydroepiandrosterone 3- in high yield (over 90%). This protection prevents unwanted side reactions at the 3-position and facilitates purification in later steps. The 17-ketone of this intermediate then undergoes with 3-pyridylmagnesium bromide, a prepared from 3-bromopyridine and magnesium in or , to form the tertiary alcohol at C-17. The occurs stereoselectively due to the steric hindrance of the steroidal framework, predominantly yielding the (17R)-. Subsequent of this alcohol under acidic conditions (e.g., using in ) eliminates water to generate the 17-(3-pyridyl)-Δ^{16} unsaturation, affording crude abiraterone , which is purified by or recrystallization to achieve pharmaceutical grade. The overall yield for this route is approximately 20-30%, limited by the step's potential for side products like over-oxidation. Industrial-scale production, optimized by Janssen Pharmaceutica following their acquisition of rights in the early , favors palladium-catalyzed cross-coupling reactions to enhance efficiency, scalability, and impurity control. A representative method involves first preparing 17-haloandrosta-5,16-dien-3β-ol (e.g., the 17-iodo derivative) from dehydroepiandrosterone via allylic or enol formation followed by halide exchange. This vinyl then couples with 3-pyridylboronic acid or its pinacol ester via Suzuki-Miyaura reaction, using a catalyst like Pd(dppf)Cl_2 in the presence of a base such as in a of and at elevated temperature (80-100°C). This stereospecific coupling directly installs the Δ^{16}-pyridyl moiety without an intermediate alcohol, achieving yields of 70-85% for the key step and overall process yields of 40-50%. Alternative couplings, such as Negishi (zinc-mediated) or Stille (stannane-based), have been explored for specific advantages in reagent stability. Quality control in synthesis emphasizes monitoring impurities, particularly the Δ^4-isomer arising from migration of the Δ^5 under basic or thermal conditions, which is limited to below 0.5% through optimized and controls during . Chiral purity at the steroidal centers, inherited from enantiopure DHEA, exceeds 99% as verified by HPLC and NMR. The final , if not performed earlier, confirms the , which improves oral absorption by enhancing and passive diffusion across membranes compared to the free alcohol. Recent innovations include process intensifications using (DoE) and (QbD) principles to minimize solvent use and maximize throughput, with patents post-2020 addressing micronized crystalline forms for better without altering the core synthetic route.

History

Discovery and development

Abiraterone acetate was discovered in the early at the Institute of Cancer Research (ICR) in , , by a team led by Mike Jarman, along with and Gerry Potter. The compound, initially known as CB7598, emerged from a screening of analogs aimed at identifying potent inhibitors of the enzyme cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17), which catalyzes key steps in biosynthesis. This effort was inspired by earlier observations that the antifungal drug could suppress but lacked specificity, prompting the search for a targeted alternative to treat by blocking testosterone production. Preclinical studies demonstrated abiraterone's high potency as a CYP17 inhibitor, with in vitro values of 2-4 nM against the enzyme's hydroxylase and lyase activities in testicular microsomes. In models, led to greater than 90% suppression of plasma testosterone levels, alongside reductions in androgen-dependent organ weights, confirming its ability to disrupt steroidogenesis without significant off-target effects on other enzymes at therapeutic doses. To improve due to abiraterone's poor aqueous , the acetate form was developed, enhancing absorption while maintaining the parent compound's selectivity. Early clinical development began with Phase I trials in the mid-2000s at the ICR and , led by investigators including Ian Judson and Johann de Bono, which confirmed the drug's safety profile and biological activity in patients with castration-resistant (CRPC). These studies showed rapid and profound reductions in serum testosterone and (PSA) levels in castrate men, validating CYP17 inhibition as a viable strategy even in advanced disease. In 2004, Cougar Biotechnology licensed the compound from BTG plc (which had acquired rights from the ICR), enabling accelerated progression into larger trials. Key milestones included the initiation of Phase II trials in 2006, which expanded on Phase I findings by demonstrating clinical responses in chemotherapy-naïve CRPC patients, and Phase III trials starting in 2009, including the pivotal COU-AA-301 study in post-chemotherapy settings. That same year, acquired Cougar Biotechnology for approximately $1 billion, providing resources to complete global development and support regulatory submissions. These efforts culminated in approvals in 2011, marking abiraterone acetate as the first CYP17 inhibitor for clinical use. Development faced challenges, notably a pronounced food effect where meals increased abiraterone exposure by 5- to 10-fold, leading to initial recommendations for administration under conditions to ensure consistent and minimize toxicity risks like and from mineralocorticoid excess. As of 2025, abiraterone acetate remains foundational for the design of next-generation CYP17 inhibitors, influencing ongoing efforts to develop agents with improved selectivity and reduced side effects.

Regulatory approvals

Abiraterone acetate, marketed as Zytiga, received initial approval from the on April 28, 2011, for the treatment of patients with metastatic castration-resistant (mCRPC) who had previously received , in combination with . The granted marketing authorization for Zytiga on September 5, 2011, for the same indication in adult men. In December 2012, the FDA expanded the indication for Zytiga to include patients with mCRPC who had not received prior , based on data from the COU-AA-302 demonstrating improved overall . Further expansion occurred on February 8, 2018, approving abiraterone acetate with for high-risk metastatic castration-sensitive (mCSPC), supported by the and trials showing benefits in radiographic and overall . On May 23, 2018, the FDA approved Yonsa, a fine-particle formulation of abiraterone acetate, in combination with for mCRPC, allowing for reduced tablet burden due to enhanced . The fixed-dose combination of abiraterone acetate and niraparib, branded as Akeega, was approved by the EMA on April 19, 2023, with prednisone or prednisolone for BRCA-mutated mCRPC in adults, following results from the MAGNITUDE trial indicating improved radiographic progression-free survival. The FDA approved Akeega on August 11, 2023, for the same indication in patients with deleterious or suspected deleterious BRCA mutations, also based on MAGNITUDE data. Abiraterone acetate was added to the World Health Organization's Model List of in 2019 as a complementary for mCRPC and remains listed in the 23rd edition (2023) and subsequent updates through 2025. It is approved in over 100 countries worldwide, including , , , and the . Generic versions began entering markets starting around 2019 in the United States following patent resolutions, with approvals for abiraterone acetate tablets in 2020 by companies such as ; in , generics were available shortly after branded launch in 2012; and in the , multiple generics like Abiraterone Accord and Abiraterone Mylan received EMA authorization in 2021. Labeling for abiraterone acetate includes warnings for , with monitoring recommendations for liver function; these emphasize the risk of severe , including rare cases of fulminant , requiring discontinuation if ALT or AST exceed 20 times the upper limit of normal. No pediatric exclusivity has been granted, as the drug lacks indications for pediatric use. There have been no major withdrawals or restrictions, though post-marketing continues to monitor adverse events such as cardiac toxicities and globally.

Society and culture

Names and formulations

Abiraterone acetate is the (INN) and (USAN) for the acetate ester prodrug of abiraterone, the active moiety that inhibits 17A1 (). The compound's systematic IUPAC name is [(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(pyridin-3-yl)-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopentaphenanthren-3-yl] , and it is also known by the developmental CB-7630 (with CB-7598 referring to the parent abiraterone). Pharmaceutical formulations of abiraterone acetate are designed for to enhance of the poorly soluble active moiety. The original is a 250 mg film-coated tablet, containing excipients such as lactose monohydrate (198.65 mg per tablet), , , croscarmellose sodium, colloidal , and for coating. A micronized tablet , with particle sizes reduced to 200–800 nanometers for improved dissolution and reduced food effect, is available as 125 mg tablets (typically dosed at 500 mg daily as four tablets). This micronized form addresses limitations in the conventional tablet by allowing administration without regard to meals while maintaining at lower doses. A fixed-dose combination tablet incorporates abiraterone with the niraparib, providing 500 mg abiraterone and 100 mg niraparib per tablet (starting dose of two tablets daily for 1,000 mg abiraterone and 200 mg niraparib). Excipients in these tablets include and , consistent with standalone formulations to ensure stability and compatibility. An investigational oral suspension formulation (e.g., 250 mg granules for reconstitution) has been developed using micronized powder to further improve and suit patients with swallowing difficulties, though it remains in clinical evaluation as of 2023. All approved tablet formulations are stored at controlled (20–25°C, with excursions permitted to 15–30°C) and have a of 24 months when protected from moisture. The micronized powder in specialized formulations enhances dissolution rates without alcohol content, supporting compliance in suspension-like preparations.

Brand names and availability

Abiraterone is primarily marketed under the brand name Zytiga by , which is available worldwide for the treatment of metastatic . Another key brand is Yonsa, developed by as a fine-particle (micronized) tablet formulation specifically approved for use . Additionally, Akeega, a dual-action tablet combining abiraterone with niraparib, is marketed by Janssen and approved in both the and the for patients with BRCA-mutated metastatic castration-resistant . Generic versions of abiraterone acetate became available in the United States following patent expirations and approvals starting in late 2018, with launches by manufacturers including and (now part of ). In the , generics such as Abiraterone Accord and Abiraterone received marketing authorizations starting in 2021, with broader market entry after the expired in September 2022. However, availability remains limited in many low- and middle-income countries due to regulatory and barriers. litigation continues regarding formulations, potentially affecting generic entry for those products. The drug is widely accessible in and through both branded and generic channels, while in regions like and , generics dominate the market, with multiple local manufacturers offering affordable 250 mg tablet alternatives such as Abirapro (Glenmark), Xbira (Cipla), Samtica (Samarth), Abirakast (Aprazer Healthcare), and Zelgor (Sun Pharma), and formulations from Dr. Reddy's. To support access , Janssen offers the CarePath program, which provides assistance including copay savings and free medication for eligible uninsured patients.

Economics and access

Abiraterone acetate was introduced in the United States in 2011 under the brand name Zytiga at a wholesale acquisition of approximately $5,000 per month, equating to roughly $60,000 annually for a typical treatment course. By 2025, the availability of generic versions has significantly lowered prices, with some suppliers offering a month's supply (120 tablets of 250 mg) for as low as $120 to pharmacies, though average out-of-pocket without or assistance programs can reach retail prices exceeding $7,000 per month ($80,000+ annually); with , copays, or discount programs, annual often range from $10,000 to $20,000 depending on coverage, dosage, and location. The combination product Akeega (niraparib and abiraterone acetate), approved in 2023, carries a higher of about $147 per tablet, resulting in an annual exceeding $100,000 for standard dosing. Prior to widespread generic entry in late 2018, Zytiga achieved peak annual global sales of approximately $2.5 billion in 2017, driven by its role in metastatic castration-resistant treatment. By 2025, amid competition from alternatives like , abiraterone's market share in the global therapeutics sector has stabilized at around 19-20%, reflecting a mature but competitive landscape valued at approximately $19 billion overall. Sales have declined post-patent expiry, with 2023 revenues for Zytiga at $887 million globally. Cost-effectiveness analyses indicate that abiraterone acetate provides quality-adjusted life-year (QALY) gains of 0.5 to 1.0 compared to standard in metastatic settings, with incremental cost-effectiveness ratios (ICERs) ranging from $38,000 to $58,000 per QALY gained in high-income countries, rendering it favorable under typical willingness-to-pay thresholds like $ per QALY. Generic formulations further improve affordability, yielding ICERs as low as $57,000 per QALY. The Institute for Clinical and Economic Review (ICER) has assessed abiraterone as providing adequate value in advanced when used appropriately in resource-rich environments. Access to abiraterone acetate remains uneven globally, with high out-of-pocket costs posing barriers in low- and middle-income countries (LMICs), where financial strain on patients and health systems limits uptake despite improved survival benefits. In the United States, insurance coverage varies; under , the (IRA) of 2022 imposes an out-of-pocket cap of $2,000 annually starting in 2025, easing burdens for eligible beneficiaries, though and step therapy requirements persist. High-income countries account for the majority of availability, with estimates suggesting over 70% of global distribution concentrated there due to regulatory approvals and reimbursement structures. Recent developments include enhanced generic penetration in LMICs through initiatives like the World Health Organization's essential medicines list—in which abiraterone acetate has been included since 2019—and voluntary licensing agreements, which have facilitated affordable supply in resource-limited settings since 2020. In the , the IRA's Medicare Drug Price Negotiation Program, with selections announced in 2024 for implementation in 2027, has not yet targeted abiraterone due to generic competition, but it continues to influence broader pricing dynamics for therapies.

Research directions

Ongoing clinical trials

As of November 2025, numerous clinical trials involving abiraterone acetate remain active or in follow-up on , exceeding 50 studies globally, with a focus on optimizing its use in metastatic through combinations and stratification. The phase 3 AMPLITUDE trial (NCT04497844) is a major ongoing randomized, double-blind, placebo-controlled study evaluating niraparib combined with abiraterone acetate plus versus abiraterone acetate plus alone in patients with metastatic castration-sensitive (mCSPC) and alterations in repair (HRR) genes. The primary endpoint is radiographic (rPFS), with secondary endpoints including overall survival and safety. Sponsored by Janssen Research & Development, the trial began recruitment in 2020 and is estimated to complete in 2027, with interim results from 2025 showing a significant rPFS benefit for the combination ( 0.65), positioning it as a potential new standard for HRR-altered mCSPC. Safety profiles were consistent with known effects, including manageable rates of and . Combination studies with are exploring abiraterone acetate alongside inhibitors in metastatic castration-resistant (mCRPC). For instance, cohort D of the phase 1b/2 KEYNOTE-365 trial (NCT02861573) assessed plus abiraterone acetate and in chemotherapy-naïve mCRPC patients, with ongoing follow-up through 2026 demonstrating antitumor activity, including a 25% objective response rate and median rPFS of 6.3 months, alongside acceptable toxicity dominated by immune-related adverse events. The primary endpoints were safety and objective response rate. Beyond the approved niraparib-abiraterone combination (Akeega), trials are investigating abiraterone acetate with other like in mCRPC. The phase 1 study of pocenbrodib (a ) alone or combined with abiraterone acetate, , or 177Lu-PSMA-617 (NCT06785636) is recruiting, focusing on safety and preliminary antitumor activity in metastatic castration-resistant , with primary endpoints of dose-limiting toxicities and recommended phase 2 dose; estimated completion is 2028. Sponsored by Pathos AI, it targets patients progressed on prior therapies. Biomarker-focused trials are incorporating advanced for selection. Limited phase 1/2 explorations in rare pediatric applications, such as , are also active but represent a small of trials. Studies with a global scope include those addressing ethnic variations, such as the phase 3 trial in Asian populations (NCT06768255) comparing generic abiraterone (300 mg) to branded formulations in mCRPC, with primary endpoint of steady-state testosterone suppression; recruiting in , estimated completion 2027, to assess efficacy and across ethnicities. Interim 2024-2025 data from arms indicate 15-25% reductions in progression risk compared to abiraterone monotherapy, with profiles aligning with established risks like excess, though combinations show slightly higher rates of and gastrointestinal events.

Investigational uses

Abiraterone acetate, through its inhibition of , has been explored in preclinical and early-phase clinical studies for applications in -driven or steroid-dependent conditions outside its established indications. These investigations aim to harness the drug's ability to suppress in contexts where hormonal dysregulation contributes to disease progression, such as certain hormone receptor-positive cancers and endocrine disorders. In breast cancer, phase II trials have evaluated abiraterone acetate in (AR)-positive, triple-negative subtypes, where androgen signaling may drive tumor growth. A multicenter, single-arm study in women with AR-positive (≥10% by immunohistochemistry), estrogen receptor-negative, progesterone receptor-negative, and HER2-negative metastatic or locally advanced disease reported a clinical benefit rate of 20% at 6 months, including one complete response and five cases of stable disease lasting at least 6 months, with a median of 2.8 months. Objective response rates were modest at 6.7%, and the treatment was generally well-tolerated with grade 1-2 adverse events like and predominating. Similar exploratory efforts in receptor-positive metastatic , often combined with or , have shown preliminary activity in postmenopausal patients progressing after nonsteroidal inhibitors, though benefits remain limited to subsets with AR pathway activation. For , particularly recurrent platinum-resistant cases, abiraterone acetate has been tested in combination with to target potential AR pathway involvement. The phase II trial, evaluating abiraterone plus in heavily pretreated patients, demonstrated an overall response rate of approximately 10%, with 14% progression-free at 6 months and a subset achieving sustained partial responses lasting over 12 months, suggesting a benefit in AR-expressing tumors from a 2016 analysis. However, the trial was halted early due to overall low efficacy, highlighting challenges in broader application. Beyond oncology, abiraterone acetate shows promise in non-malignant steroid-dependent disorders. In (CAH), phase II explorations and case series have assessed its role in controlling excess precursors by further inhibiting adrenal steroidogenesis alongside replacement. A 2024 case report in a patient with classic CAH reported significant reductions in 11-oxygenated s and levels with low-dose abiraterone acetate, enabling better hormonal balance without excessive accumulation when combined appropriately. Similarly, limited preclinical and early human data indicate potential for modulation in (PCOS), where overactivity contributes to ; models and small cohorts of women with excess demonstrated suppressed testosterone and 11-ketotestosterone production, though clinical translation remains exploratory due to sparse phase II evidence. Investigational combinations seek to enhance abiraterone acetate's efficacy in resistant settings. Pairing with AKT inhibitors addresses compensatory PI3K/AKT pathway activation post-androgen deprivation; a randomized phase II trial of ipatasertib plus abiraterone in metastatic castration-resistant with PTEN loss showed improved radiographic (11.5 months vs. 4.6 months; 0.39), though overall tolerability was moderate with grade ≥3 events like in 39%. Earlier phase I studies with dual PI3K/ like BEZ235 confirmed feasibility but noted dose-limiting toxicities at higher levels, limiting advancement without refinements. Abiraterone acetate has also been probed for radiosensitization in localized , where androgen suppression may augment radiotherapy effects on tumor proliferation. A phase II trial combining abiraterone with short-term androgen deprivation and achieved profound prostatic suppression (testosterone <0.7 nmol/L in 95% of patients) and was deemed safe, with no excess genitourinary or gastrointestinal toxicities beyond standard radiation effects. These expansions leverage CYP17 inhibition's broad impact on steroidogenesis in androgen- or glucocorticoid-dependent pathologies, but face hurdles including mixed efficacy in non-prostate malignancies (e.g., failure to progress to phase III in ovarian trials) and heightened toxicity risks like hypokalemia or hypertension in non-androgen-driven contexts without prednisone co-administration. Preclinical data up to 2024 suggest potential in neuroendocrine-differentiated prostate tumors via sustained androgen blockade, though human translation awaits further validation.

References

  1. https://medlineplus.gov/druginfo/meds/a611046.html
  2. https://www.cancer.gov/about-cancer/treatment/drugs/abirateroneacetate
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC3267518/
  4. https://www.drugs.com/history/zytiga.html
  5. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-abiraterone-acetate-combination-prednisone-high-risk-metastatic-castration-sensitive
  6. https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA5078
  7. https://www.nature.com/articles/s41591-025-03961-8
  8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202379s031s033lbl.pdf
  9. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca-mutated-metastatic-castration
  10. https://pubmed.ncbi.nlm.nih.gov/22995653/
  11. https://www.nejm.org/doi/full/10.1056/NEJMoa1704174
  12. https://pubmed.ncbi.nlm.nih.gov/35411939/
  13. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210308s000lbl.pdf
  14. https://www.yonsarx.com/dosing
  15. https://www.drugs.com/dosage/abiraterone.html
  16. https://www.ema.europa.eu/en/documents/product-information/zytiga-epar-product-information_en.pdf
  17. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202379s035lbl.pdf
  18. https://www.ema.europa.eu/en/documents/rmp/zytiga-epar-risk-management-plan_en.pdf
  19. https://www.zytigahcp.com/efficacy-and-safety/
  20. https://www.ema.europa.eu/en/medicines/human/EPAR/zytiga
  21. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=88d05db3-8bdc-47f1-bb00-6b4a71f98609
  22. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202379orig1s000clinpharmr.pdf
  23. https://www.hiv-druginteractions.org/interactions/2104/all
  24. https://go.drugbank.com/drugs/DB05812
  25. https://pmc.ncbi.nlm.nih.gov/articles/PMC10053955/
  26. https://pubmed.ncbi.nlm.nih.gov/35037798/
  27. https://pubmed.ncbi.nlm.nih.gov/39465560/
  28. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216793s000lbl.pdf
  29. https://www.mayoclinic.org/drugs-supplements/abiraterone-oral-route/description/drg-20074889
  30. https://www.cancercareontario.ca/en/drugformulary/drugs/infosheet/44251
  31. https://www.chemoexperts.com/abiraterone-zytiga-prednisone.html
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC3047603/
  33. https://pmc.ncbi.nlm.nih.gov/articles/PMC4023364/
  34. https://pmc.ncbi.nlm.nih.gov/articles/PMC2935850/
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC8169043/
  36. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202379lbl.pdf
  37. https://pmc.ncbi.nlm.nih.gov/articles/PMC3405235/
  38. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781616
  39. https://www.jci.org/articles/view/98319
  40. https://www.mdpi.com/1422-0067/25/11/6058
  41. https://pubchem.ncbi.nlm.nih.gov/compound/Abiraterone-Acetate
  42. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202379Orig1s000ChemR.pdf
  43. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=be29365a-ed25-44c0-9818-e9016dc95ba6
  44. https://pmc.ncbi.nlm.nih.gov/articles/PMC8582395/
  45. https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00442
  46. https://pmc.ncbi.nlm.nih.gov/articles/PMC4506215/
  47. https://pubs.acs.org/doi/10.1021/acs.oprd.6b00215
  48. https://patents.google.com/patent/CN105713063A/en
  49. https://patents.google.com/patent/CN104558091A/en
  50. https://patents.google.com/patent/CN103242410A/en
  51. https://pmc.ncbi.nlm.nih.gov/articles/PMC11238291/
  52. https://www.sciencedirect.com/science/article/abs/pii/S0039128X22000265
  53. https://www.icr.ac.uk/about-us/icr-news/detail/a-new-way-to-treat-prostate-cancer-the-story-of-abiraterone
  54. https://encyclopedia.pub/entry/34436
  55. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/202379Orig1s000PharmR.pdf
  56. https://link.springer.com/article/10.1007/s00280-012-1916-9
  57. https://pmc.ncbi.nlm.nih.gov/articles/PMC2849769/
  58. https://www.biospace.com/b-btg-b-licenses-new-prostate-cancer-drug-to-cougar-biotechnology
  59. https://pubmed.ncbi.nlm.nih.gov/18645193/
  60. https://www.nejm.org/doi/full/10.1056/NEJMoa1014618
  61. https://www.fiercebiotech.com/biotech/j-j-buys-cougar-biotech-for-1b
  62. https://www.sciencedirect.com/science/article/pii/S0928098722001397
  63. https://onlinelibrary.wiley.com/doi/10.1038/clpt.2011.275
  64. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202379Orig1s005.pdf
  65. https://www.ema.europa.eu/en/medicines/human/EPAR/akeega
  66. https://list.essentialmeds.org/medicines/406
  67. https://www.drreddys.com/media/904727/press-release-_-abiraterone-acetate-tab-250mg.pdf
  68. https://www.ema.europa.eu/en/medicines/human/EPAR/abiraterone-accord
  69. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2f932015-28b2-4f44-ac04-772e982e13e9
  70. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/abiraterone-acetate
  71. https://www.yonsarx.com/
  72. https://pmc.ncbi.nlm.nih.gov/articles/PMC8705659/
  73. https://www.ema.europa.eu/en/documents/product-information/akeega-epar-product-information_en.pdf
  74. https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5052
  75. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210308Orig1s000ChemR.pdf
  76. https://www.zytiga.com/
  77. https://www.drugs.com/availability/generic-yonsa.html
  78. https://akeegahcp.com/
  79. https://www.drugpatentwatch.com/p/generic/abiraterone%2Bacetate
  80. https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0044-1782235.pdf
  81. https://www.ema.europa.eu/en/medicines/human/EPAR/abiraterone-mylan
  82. https://www.jnj.com/media-center/press-releases/court-issues-ruling-in-zytiga-patent-infringement-litigation
  83. https://synapse.patsnap.com/article/the-patent-landscape-of-abiraterone-acetate
  84. https://www.exportersindia.com/indian-suppliers/abiraterone-acetate-tablets.htm
  85. https://www.1mg.com/drugs/abirapro-250mg-tablet-161430
  86. https://www.navlindaily.com/article/9091/abiraterone-acetate-becomes-first-indian-oncology-therapy-to-be-marketed-in-china
  87. https://www.janssencarepath.com/hcp/zytiga/affordability
  88. https://www.nytimes.com/2011/06/28/health/28prostate.html
  89. https://civicarx.org/civicascript-lowers-price-of-its-generic-abiraterone-tablets/
  90. https://www.goodrx.com/abiraterone
  91. https://www.ncbi.nlm.nih.gov/books/NBK604454/
  92. https://www.biopharmadive.com/news/johnson-zytiga-q2-earnings-pharmaceutial-revenue/527966/
  93. https://www.grandviewresearch.com/industry-analysis/prostate-cancer-therapeutics-market
  94. https://www.globaldata.com/data-insights/healthcare/the-global-drug-sales-of-zytiga-1127405/
  95. https://www.valueinhealthjournal.com/article/S1098-3015%2821%2903182-X/fulltext
  96. https://ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.358
  97. https://icer.org/wp-content/uploads/2020/10/ICER_Prostate_Cancer_Evidence_Presentation_100418.pdf
  98. https://pmc.ncbi.nlm.nih.gov/articles/PMC12580529/
  99. https://www.urologytimes.com/view/inflation-reduction-act-may-lower-patients-medicare-costs-for-prostate-cancer-treatment
  100. https://www.biospace.com/abiraterone-acetate-included-in-world-health-organisation-s-essential-medicines-list-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer
  101. https://www.ijmpo.org/assets/articles/is-low-dose-abiraterone-for-prostate-cancer-an-attractive-strategy-for-limited-resource-settings.pdf
  102. https://pmc.ncbi.nlm.nih.gov/articles/PMC11522450/
  103. https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA5006
  104. https://pubmed.ncbi.nlm.nih.gov/38926066/
  105. https://www.sciencedirect.com/science/article/pii/S2588931124001457
  106. https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-02182
  107. https://www.clinicaltrials.gov/study/NCT06768255
  108. https://www.mdpi.com/2072-6694/17/17/2747
  109. https://pubmed.ncbi.nlm.nih.gov/27052658/
  110. https://ascopubs.org/doi/10.1200/jco.2014.32.15_suppl.519
  111. https://www.targetedonc.com/view/setback-for-abiraterone-acetate-in-recurrent-ovarian-cancer
  112. https://academic.oup.com/jcemcr/article/2/6/luae077/7681113
  113. https://www.sciencedirect.com/science/article/abs/pii/S0960076017302558
  114. https://pmc.ncbi.nlm.nih.gov/articles/PMC7096060/
  115. https://aacrjournals.org/clincancerres/article/25/3/928/9678/Randomized-Phase-II-Study-Evaluating-Akt-Blockade
  116. https://pubmed.ncbi.nlm.nih.gov/28314838/
  117. https://pmc.ncbi.nlm.nih.gov/articles/PMC4459893/
  118. https://www.sciencedirect.com/science/article/pii/S266700542500047X
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