CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Iclusig (ponatinib) therapy

Defines accepted indications, continuation and exclusion criteria, dosing limits, safety warnings, and billing code for Iclusig (ponatinib) across commercial, CHIP, Exchange, Medicaid, and Medicare Advantage lines of business. Specifies evidentiary standards for off-label uses and continuation rules for previously authorized therapy.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyIclusig (ponatinib) therapy

Policy CodePolicy N/A

Change TypeTemplate conversionclinical updates (ALL indications)

Effective Date

Next Review Date

Key ActionProviders must supply evidence from FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature to support medication use and off-label requests.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template (April 2025).

April 2024 updates to ALL indication and exclusion criteria.

5Covered Indication Lines (ALL/CML variants + continuation rules)

4Exclusion Criteria Items

1Billing HCPCS Code

Coverage Summary

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Scope: Defines accepted indications for Iclusig (ponatinib) including FDA-approved and selected off-label uses supported by recognized compendia/guidelines. Covered uses include: Philadelphia chromosome/BCR‑ABL positive Acute Lymphoblastic Leukemia (ALL) — Iclusig may be used in combination with chemotherapy for adult members with newly diagnosed Ph+ ALL, and as single agent for Ph+ ALL with documented intolerance/contraindication/progression on imatinib or for T315I mutation–positive disease. For Chronic Myeloid Leukemia (CML), Iclusig may be used as a single agent for subsequent‑line therapy after documented intolerance/contraindication/progression on imatinib and one other TKI (nilotinib or dasatinib), or for T315I mutation–positive CML.

Continuation rules: Continuation requests for a not‑approvable medication are exempt provided all conditions are met: member has not experienced disease progression on Iclusig, the medication was used within the last year without a lapse of more than 30 days of active authorization, and no additional medications are being added to the continuation request.

Coverage stance and lines of business: Coverage stance = covered_with_criteria. Applicable lines of business: Commercial, CHIP, Exchange/Marketplace, Medicaid, and Medicare Advantage.

Initial Therapy Criteria (Covered Uses)

Acute Lymphoblastic Leukemia (ALL) - Covered Uses

Iclusig (ponatinib) may be used when ANY of the following conditions are met:

ANY of the following

Alternative when imatinib intolerance/progression
- The member has Philadelphia chromosome/BCR-ABL positive ALL
- Documented intolerance, contraindication, or disease progression on generic imatinib
T315I mutation
- Member has T315I mutation positive Philadelphia chromosome/BCR-ABL positive ALL
- Ponatinib may be used as a single agent

Chronic Myeloid Leukemia (CML) - Covered Uses

Iclusig (ponatinib) may be used when ANY of the following conditions are met:

ANY of the following

Subsequent-line therapy after intolerance/progression
- Documented intolerance, contraindications, or disease progression on generic imatinib
- AND documented intolerance, contraindications, or disease progression on one other TKI: Tasigna (nilotinib) or Sprycel (dasatinib)
T315I mutation
- Member has T315I mutation positive CML
- Ponatinib may be used as a single agent

Continuation Therapy Criteria

General Continuation Exception

Continuation requests for a not-approvable medication shall be exempt provided ALL conditions are met:

ALL of the following

The member has not experienced disease progression on the requested medication
The requested medication was used within the last year without a lapse of more than 30 days of having an active authorization
Additional medication(s) are not being added to the continuation request

Exclusion Criteria / Not Covered

Iclusig (ponatinib) is excluded when ANY of the following are present:

ANY of the following

Disease progression while taking Iclusig (ponatinib)
Use for treatment of members with newly diagnosed CML without the T315I mutation
Concurrent use with other anticancer therapies for the treatment of CML
Use of T315I mutation negative ALL if used as monotherapy
Monthly maximum tablet quantity exceeded
- Treatment exceeds the maximum limit of 30 (10 mg) tablets/month
- Treatment exceeds the maximum limit of 30 (15 mg) tablets/month
- Treatment exceeds the maximum limit of 30 (30 mg) tablets/month
- Treatment exceeds the maximum limit of 30 (45 mg) tablets/month
Dosing exceeds single dose limit of Iclusig (ponatinib) 45 mg45 mg
Investigational use for an off-label indication that lacks sufficient evidence or is not accepted by the medical community (not supported by CMS recognized compendia or acceptable peer-reviewed literature)

Safety exclusions and warnings: Iclusig includes US boxed warnings for arterial occlusive events (AOEs) — including fatal myocardial infarction, stroke, large arterial stenosis, severe peripheral vascular disease, and need for urgent revascularization — as well as venous thromboembolic events (VTEs), heart failure (including fatalities), and hepatotoxicity (including liver failure and death). Monitoring and interruption/discontinuation guidance is recommended based on severity.

Investigational/off‑label exclusion rationale: Off‑label uses that are not supported by sufficient evidence or not generally accepted by the medical community may be excluded. Sufficiency is defined by representation of relevant patient and regimen characteristics, clinically meaningful outcomes per ASCO definitions (e.g., HR < 0.80 and recommended survival benefits), appropriate study design, and reliance on CMS‑recognized compendia or acceptable peer‑reviewed literature per the Medicare Benefit Policy Manual.

Provider Actions & Authorization Requirements

Prior Authorization

Evidence requirements for coverage

Medication use must be supported by FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements. Providers must supply such evidence for off-label uses to obtain coverage.

J8999
Accepted sources: FDA labeling; CMS-recognized compendia; NCCN/ASCO guidelines; peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15

Documentation Required

Document intolerance/contraindication/progression

When ponatinib is requested after prior TKIs or as a substitute for imatinib, document the member’s intolerance, contraindication, or disease progression on the prior agent(s) (generic imatinib and, where applicable, nilotinib or dasatinib).

Documentation Required

Mutation status required for certain indications

For indications permitting single‑agent ponatinib use, providers must document T315I mutation positivity (e.g., T315I mutation positive CML or ALL) in the medical record.

Billing Rule

Dose and quantity limits

Claims exceeding the single‑dose limit of 45 mg or exceeding monthly tablet quantity limits are excluded and may be denied. Adhere to single‑dose 45 mg maximum and monthly tablet limits by strength.

Monthly limits: 30 tablets per month for each strength — 10 mg, 15 mg, 30 mg, 45 mg
Affected billing code: J8999

Denial Risk

Exclusion for investigational/off-label insufficient evidence

Requests for investigational or off‑label uses that lack sufficient evidence or are not accepted by the medical community — i.e., not supported by CMS‑recognized compendia or acceptable peer‑reviewed literature meeting CMS standards — may be denied as investigational.

Clinical Evidence & References

Evidence:

• Jabbour E et al. Ponatinib vs Imatinib in Frontline Philadelphia Chromosome‑Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA 2024.

• Iclusig prescribing information. Takeda Pharmaceuticals America, Inc. 2024.

• NCCN Cancer Guidelines and Drugs & Biologics Compendium 2025; ASCO guidance and other CMS‑recognized compendia references (2025).

Background

Background and policy scope: This policy defines accepted uses of Iclusig (ponatinib), including FDA‑approved indications and selected off‑label uses supported by CMS‑recognized compendia, NCCN/ASCO guidelines, or acceptable peer‑reviewed literature. Evolent is responsible for processing medication requests and authorizations; medication use must be supported by FDA labeling, CMS‑recognized compendia, NCCN/ASCO guidance, or peer‑reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.

Safety warnings summary: Iclusig carries US boxed warnings for arterial occlusive events (AOEs), venous thromboembolic events (VTEs), heart failure, and hepatotoxicity. Patients should be monitored and therapy interrupted or discontinued based on severity.

Operational note: Evolent processes all medication requests from ordering providers; medications not authorized by Evolent may be deemed not approvable and not reimbursable. Continuation exemption criteria apply when no progression, no authorization lapse > 30 days in the prior year, and no additional medications are added to the continuation request.

Revision History

2024-04material_change

Updated ALL indication section to include use with chemotherapy for adult members with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); updated verbiage and added reference; updated exclusion criteria.

2025-04conversion_noteLatest

Converted to new Evolent guideline template; updated maximum dosage form quantities in exclusion criteria.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyIclusig (ponatinib) therapy

Policy CodePolicy N/A

Change TypeTemplate conversionclinical updates (ALL indications)

Effective Date

Next Review Date

Key ActionProviders must supply evidence from FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature to support medication use and off-label requests.

SourceLink

On This Page

OpenPayer

Iclusig (ponatinib) therapy

Coverage Summary

Initial Therapy Criteria (Covered Uses)

Continuation Therapy Criteria

Exclusion Criteria / Not Covered

Applicable Codes

Provider Actions & Authorization Requirements

Clinical Evidence & References

Background

Revision History