Ponatinib

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title: "Ponatinib" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["non-receptor-tyrosine-kinase-inhibitors", "drugs-developed-by-takeda-pharmaceutical-company", "alkyne-derivatives", "benzanilides", "imidazopyridazines", "4-methylpiperazin-1-yl-compounds", "(trifluoromethyl)benzene-derivatives"] description: "Medication" topic_path: "general/non-receptor-tyrosine-kinase-inhibitors" source: "https://en.wikipedia.org/wiki/Ponatinib" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Medication ::

::data[format=table title="Infobox drug"]

Field	Value
image	Ponatinib2DACS.svg
image_class	skin-invert-image
width	275
image2	Ponatinib molecule ball.png
image_class2	bg-transparent
pronounce
tradename	Iclusig
Drugs.com
MedlinePlus	a613029
DailyMedID	Ponatinib
pregnancy_AU	D
routes_of_administration	By mouth
ATC_prefix	L01
ATC_suffix	EA05
legal_AU	S4
legal_AU_comment
legal_BR
legal_CA	Rx-only
legal_CA_comment
legal_DE
legal_NZ
legal_UK
legal_US	Rx-only
legal_US_comment
legal_EU	Rx-only
legal_EU_comment
legal_UN
legal_status
bioavailability	Unknown
protein_bound	99% (in vitro)
metabolism	Liver (CYP3A4, 2C8, 2D6, 3A5)
elimination_half-life	12–66 hours
excretion	Feces (87%), urine (5%)
CAS_number	943319-70-8
PubChem	24826799
DrugBank	DB08901
ChemSpiderID	24747381
UNII	4340891KFS
KEGG	D09950
ChEBI	78543
ChEMBL	1171837
synonyms	AP24534
IUPAC_name	3-(2-Imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide
C	29
SMILES	Cc1ccc(cc1C#Cc2cnc3n2nccc3)C(=O)Nc4ccc(c(c4)C(F)(F)F)CN5CCN(CC5)C
StdInChI	1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39)
StdInChIKey	PHXJVRSECIGDHY-UHFFFAOYSA-N
::

| image = Ponatinib2DACS.svg | image_class = skin-invert-image | width = 275 | alt = | image2 = Ponatinib molecule ball.png | image_class2 = bg-transparent | width2 = | alt2 =

| pronounce =
| tradename = Iclusig | Drugs.com = | MedlinePlus = a613029 | DailyMedID = Ponatinib | pregnancy_AU = D | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = By mouth | class = | ATC_prefix = L01 | ATC_suffix = EA05 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = | legal_BR = | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = | legal_DE = | legal_DE_comment = | legal_NZ = | legal_NZ_comment = | legal_UK = | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = | legal_EU = Rx-only | legal_EU_comment = | legal_UN = | legal_UN_comment = | legal_status =

| bioavailability = Unknown | protein_bound = 99% (in vitro) | metabolism = Liver (CYP3A4, 2C8, 2D6, 3A5) | metabolites = | onset = | elimination_half-life = 12–66 hours | duration_of_action = | excretion = Feces (87%), urine (5%)

| CAS_number = 943319-70-8 | CAS_supplemental = | PubChem = 24826799 | IUPHAR_ligand = | DrugBank = DB08901 | ChemSpiderID = 24747381 | UNII = 4340891KFS | KEGG = D09950 | ChEBI = 78543 | ChEMBL = 1171837 | NIAID_ChemDB = | PDB_ligand = | synonyms = AP24534

| IUPAC_name = 3-(2-Imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide | C=29 | H=27 | F=3 | N=6 | O=1 | SMILES = Cc1ccc(cc1C#Cc2cnc3n2nccc3)C(=O)Nc4ccc(c(c4)C(F)(F)F)CN5CCN(CC5)C | StdInChI = 1S/C29H27F3N6O/c1-20-5-6-22(16-21(20)8-10-25-18-33-27-4-3-11-34-38(25)27)28(39)35-24-9-7-23(26(17-24)29(30,31)32)19-37-14-12-36(2)13-15-37/h3-7,9,11,16-18H,12-15,19H2,1-2H3,(H,35,39) | StdInChI_comment = | StdInChIKey = PHXJVRSECIGDHY-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation =

Ponatinib, sold under the brand name Iclusig, is a medication used for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia. It was developed by Ariad Pharmaceuticals. It is a multi-targeted tyrosine-kinase inhibitor. Some forms of chronic myeloid leukemia, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors.

Ponatinib was approved for medical use in the United States in December 2012, and in the European Union in July 2013.

Medical uses

Ponatinib is indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia.

In March 2024, the FDA expanded the indication to include the treatment, with chemotherapy, for adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

Adverse effects

The US Food and Drug Administration (FDA) issued a partial clinical hold on new trial enrollment for ponatinib in October 2013, due to an increased number of blood clots observed in patients taking the drug. The EPIC trial was later canceled in October 2013. Subsequent studies of 449 patients treated during 4 years with ponatinib for chronic phase chronic myelogenous leukemia found the following adverse reactions. 150 Patients experienced cardiac vascular (21% of patients), peripheral vascular (12%), and cerebrovascular (9%) arterial occlusive events. Venous thromboembolic events occurred in 6% of patients. The most common all-grade adverse events included hypertension (69%), rash (63%), abdominal pain (48%), fatigue (47%), headache (43%), arterial ischemia (42%), dry skin (42%), constipation (41%), arthralgia (32%), nausea (28%), pyrexia (26%), peripheral neuropathy (24%), myalgia (24%), pain in extremity (23%), back pain (21%), and diarrhea (20%). In addition, there have been reported cases of the posterior reversible encephalopathy syndrome. Recently, an analogue of ponatinib was developed that retained anti-tumor efficacy but had reduced cardiovascular toxicity in experimental models.

Clinical trials

In 2010, Ariad announced result from a phase I study of ponatinib in patients with resistant and refractory chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). The study demonstrated that in chronic-phase chronic myeloid leukemia patients treated with ponatinib, 66 percent of patients in the trial achieved a major cytogenetic response, including 100 percent of patients who also had a T315I mutation.

The PACE (Ponatinib Ph+ ALL and chronic myeloid leukemia Evaluation) pivotal phase II trial started enrolling patients in September 2010 and is designed to provide definitive clinical data for regulatory approval in this setting. Good results were reported in December 2012.

The EPIC (Evaluation of Ponatinib versus Imatinib in chronic myeloid leukemia) phase-III trial began in June 2012 and was halted on October 18, 2013.

Mechanism of action

The primary target for ponatinib is BCR-ABL, an abnormal tyrosine kinase that is the hallmark of chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Chronic myeloid leukemia is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, chronic myeloid leukemia typically evolves to more aggressive phases such as accelerated or blast crisis. Philadelphia-positive acute lymphoblastic leukemia is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than chronic myeloid leukemia and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. Because both of these diseases express the BCR-ABL protein, this would render them potentially susceptible to treatment with ponatinib. BCR-ABL is detected in 95% of patients with chronic myeloid leukemia.

Society and culture

Legal status

Ponatinib was approved by the US FDA in December 2012, for people with resistant or intolerant chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia, based on results of the PACE phase II trial. Based on additional studies, the FDA granted full approval in 2016, and updated the label to include people with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia for whom no other tyrosine kinase inhibitor therapy is indicated. Approval was also granted for T315I-positive and T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia.

Economics

The medication costs $138,000 per year.

As of 2015, ponatinib is available in England for the treatment of chronic myeloid leukemia (chronic phase, accelerated phase or blast phase) and Philadelphia-positive acute lymphoblastic leukemia in patients with documented T315I mutation under the Cancer Drugs Fund, and has not been appraised by the National Institute for Health and Care Excellence (NICE), who noted the small expected patient population. NICE estimated that ponatinib would cost approximately £61,000 per year, but the price paid under the Cancer Drugs Fund is confidential and may be different. Ponatinib has generic drug available in some countries like Bangladesh and that are manufactured by some reputed Bangladeshi pharmaceuticals companies under the brand names such as Ponaxen and Ponatinix.{{Cite web |title= Ponatinib Price & Cost |url=https://emergencydrug.com/generic/ponatinib/ |website=EmergencyDrug |publisher=Emergency Drug |access-date=28 August 2025}}

References

References

1. (21 June 2022). "Prescription medicines: registration of new chemical entities in Australia, 2014".
2. (7 July 2016). "Product monograph brand safety updates".
3. (4 May 2016). "Health Canada New Drug Authorizations: 2015 Highlights".
4. (10 November 2022). "Iclusig- ponatinib hydrochloride tablet, film coated".
5. (2 February 2010). "Iclusig EPAR".
6. (June 2010). "Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant". Journal of Medicinal Chemistry.
7. (November 2009). "AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance". Cancer Cell.
8. (21 December 2012). "Drug Approval Package: Iclusig (ponatinib) 15 mg and 45 mg Tablets NDA #203469".
9. (19 March 2024). "FDA grants accelerated approval to ponatinib with chemotherapy for new".
10. (1 October 2024). "Cancer Accelerated Approvals".
11. Carroll J. (9 October 2013). "UPDATED: Ariad hammered on toxicity concerns for leukemia drug Iclusig". FierceBiotech.
12. "Ariad Announces Discontinuation of the Phase 3 Epic Trial of Iclusig in Patients with Newly Diagnosed Chronic Myeloid Leukemia".
13. (August 2022). "Reengineering Ponatinib to Minimize Cardiovascular Toxicity". Cancer Research.
14. Gever J. (Dec 10, 2012). "Ponatinib Retains Luster in Leukemia". MedPageToday.com.
15. (5 November 2014). "Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia".
16. Gever J. (Dec 14, 2012). "Ponatinib Wins Early FDA Nod". MedPageToday.com.
17. (29 November 2016). "FDA Grants Ponatinib Full Approval for Rare Leukemias".
18. Pollack A. (April 25, 2013). "Doctors Denounce Cancer Drug Prices of $100,000 a Year". The New York Times.
19. (May 2013). "The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts". Blood.
20. (May 2025). "National Cancer Drugs Fund list Ver4.3". NHS England.
21. "Consultation on Batch 33 draft remits and draft scopes and summary of comments and discussions at scoping workshops". National Institute for Health and Care Excellence..

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