OnCo
drugsProductApproved2012🇪🇺🇬🇧🇯🇵🇦🇺

Ponatinib

Ponatinib is the only BCR::ABL1 inhibitor that covers the T315I resistance mutation. In 2024 it became the preferred pill for newly diagnosed Ph-positive ALL.

PhALLCON (n=245): ponatinib vs imatinib with reduced-intensity chemotherapy in newly diagnosed Ph+ ALL, MRD-negative CR at end of induction 34.4% vs 16.7%; accelerated approval March 2024. Also approved in CML (T315I and resistant disease) since 2012, with a 2013 temporary market suspension for arterial occlusive events that led to dose-reduction strategies (OPTIC). Ponatinib + blinatumomab chemotherapy-free regimens (MD Anderson) report near-universal molecular remission without transplant.

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Ponatinib
PubChem
Mechanism, step by step
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1.Ponatinib binds the ATP pocket of BCR::ABL1, including T315I mutants

Modality
Small-molecule kinase inhibitor (pan-BCR::ABL1 incl. T315I)
Mechanism
Type II TKI binding inactive ABL1 with a carbon-carbon triple bond that accommodates the T315I gatekeeper; also inhibits FGFR, VEGFR, SRC.
Brand / code
Iclusig
Dosing & schedule
Route
Oral
Schedule
Ph+ ALL: 30 mg daily with chemotherapy, reduced to 15 mg once MRD-negative CR is achieved; CML: 45 mg daily reducing to 15 mg on response (OPTIC)
Monitoring
Arterial occlusive events, venous thromboembolism, heart failure, hepatotoxicity (boxed warnings); blood pressure; lipase

Source: US prescribing information (DailyMed). Doses are for orientation; the current label governs.

Medicare
Part D (self-administered)

Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026).

Commercial insurance
covered with prior authorisation

Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. T315I mutation or failure/intolerance of two prior TKIs, per the label.

Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.

Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.

NICE recommendedNICE TA451 · 2017SMC: accepted
Appraised for
CML or Ph-positive ALL resistant to dasatinib or nilotinib, or with T315I
NHS England
Routinely funded for the appraised indication (or via managed access)

Sources: NICE TA451 · SMC advice: ponatinib. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.

Regulatory

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  1. 14 Dec 2012ApprovalUS

    Resistant CML/Ph+ ALL

  2. 31 Oct 2013WithdrawalUS

    Temporary marketing suspension for arterial occlusion; returned with narrowed label December 2013

  3. 19 Mar 2024ApprovalUS

    Frontline Ph+ ALL (PhALLCON), accelerated

Approvals

RegionYearIndication
US2012CML and Ph+ ALL resistant to prior TKIs or with T315I
US2024Newly diagnosed Ph+ ALL with chemotherapy (accelerated)

Safety

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Toxicity profile
Adverse eventAny gradeGrade 3+
Arterial occlusive events
CML long-term data at 45 mg; lower with response-based dose reduction
26%
Hypertension
68%
Pancreatitis / lipase elevation
40%
Hepatotoxicity
Boxed warning

Rates read from the US prescribing information. Blank cells mean the figure was not sourced, not that it is zero.

Trials

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ClinicalTrials.gov · phase 2/3
refreshed 2026-09-09
61 studies11 recruiting56 Phase 28 Phase 3
Search “Ponatinib” on ClinicalTrials.gov →
Counts are from a name search and may include unrelated studies; up to 100 studies are summarised.

Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Ponatinib
intervention: Ponatinib
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

Latest papers

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Literature trend146 papers in the last 12 months+8% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this drug: (TITLE:"Ponatinib" OR ABSTRACT:"Ponatinib" OR TITLE:"Iclusig" OR ABSTRACT:"Iclusig") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Ponatinib, not a curated reading list.

Connected

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