Ponatinib (Iclusig)

General information

Class/mechanism: Tyrosine kinase inhibitor with multiple targets, including Bcr-Abl tyrosine kinase, the constitutively active tyrosine kinase resulting from the Philadelphia chromosome abnormality in CML, as well as VEGFR, PDGFR, FGFR, the SRC kinases, KIT, EPH receptors, RET, TIE2, and FLT3. Ponatinib is active against the Bcr-Abl T315I mutation.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Toxicity management

• 2013-10-31: Suspended by FDA because of the risk of life-threatening blood clots and severe narrowing of blood vessels.
• 2013-12-20: REMS program put in place and medication is once again available; REMS was discontinued in August 2018.

Diseases for which it is used

• Chronic myeloid leukemia
• Ph+ B-cell ALL

Patient drug information

• Ponatinib (Iclusig) package insert
• Ponatinib (Iclusig) patient drug information (Chemocare)
• Ponatinib (Iclusig) patient drug information (UpToDate)

History of changes in FDA indication

• 2012-12-14: Accelerated approval for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy (Based on OPTIC)
• 2012-12-14: Accelerated approval for the treatment of adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy. (Based on PACE)
• 2016-11-29: Granted full approval for the treatment of adult patients with chronic-phase, accelerated-phase, or blast-phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) for whom no other tyrosine kinase inhibitor therapy is indicated. (Based on PACE)
• 2016-11-29: Granted full approval for the treatment of adult patients with T315I­-positive CML (chronic phase, accelerated phase, or blast phase). (Based on PACE)
• 2016-11-29: Granted full approval for the treatment of adult patients with T315I­-positive, Philadelphia chromosome-positive ALL. (Based on PACE)
• 2024-03-19: Granted accelerated approval in combination with chemotherapy for adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). (Based on PhALLCON)

History of changes in EMA indication

• 2013-07-01: Initial authorization

History of changes in Health Canada indication

• 2015-04-02: Initial notice of compliance with conditions
• 2022-10-03: Conditions were met

History of changes in PMDA indication

• 2016-09-28: New approval for the treatment of chronic myelogenous leukemia with resistance or intolerance to prior drug therapies.
• 2016-09-28: New approval for the treatment of recurrent or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Also known as

• Code name: AP-24534
• Generic name: ponatinib hydrochloride
• Brand name: Iclusig