CurrentHealth NetPolicy CP.PHAR.108

CLINICAL POLICY Omacetaxine

Defines clinical coverage criteria, initial and continued therapy requirements, dosing limits, prior authorization documentation, exclusions, coding implications, and approval durations for omacetaxine (Synribo) across Commercial, HIM and Medicaid lines of business.

Policy Summary

PayerHealth Net

PolicyCLINICAL POLICY Omacetaxine

Policy CodePolicy CP.PHAR.108

Change TypeMaterial and administrative updates (2021-2025)

Effective DateApr 1, 2013

Next Review Date

Key ActionProvider must submit documentation (office chart notes, lab results, or other clinical information) supporting that member meets all approval criteria, including prior TKI therapy trials and evidence of response or intolerance.

POLICY UPDATE CHANGES

Added requirement that member has experienced resistance, toxicity, or intolerance to two or more TKIs.

Clarified dosing to allow 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle; maximum dose specified.

Added additional therapy requirement previously for T315I mutation that the member has received treatment with ponatinib (Iclusig) and asciminib (Scemblix) when other TKIs are contraindicated (later removed).

Removed off-label use in T315I mutation as this is no longer supported by NCCN Compendium.

2Q2023 and 2Q2024 annual reviews noted 'no significant changes'; references reviewed and updated.

1FDA-approved indication (CML accelerated phase with resistance/intolerance to >=2 TKIs)

>=2Required prior TKIs failed/intolerant

J9262Primary billing code

Coverage Summary

Coverage stance: covered with criteria for the FDA-approved indication of omacetaxine (Synribo). The policy (policy_number: CP.PHAR.108) is current (status: CURRENT) and defines clinical criteria for use.

FDA approval (background/scope): Synribo is indicated for the treatment of adult patients with accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). Dosing limits and schedule are specified in the policy (maximum 2.5 mg/day; induction 14 consecutive days of each 28-day cycle; maintenance 7 consecutive days of each 28-day cycle).

Key thresholds

Maximum daily dose2.5 mg/day (1.25 mg subcutaneous twice daily)

Induction dosing duration14 consecutive days of each 28-day cycle

Maintenance dosing duration7 consecutive days of each 28-day cycle

Minimum prior therapy requirementResistance, toxicity, or intolerance to >= 2 TKIs

Minimum prior Synribo exposure for continuation>= 30 days

Initial Therapy Criteria

Initial Approval Criteria

Synribo is medically necessary when ALL of the following are met:

CML-specific requirements

Diagnosis of Philadelphia chromosome (BCR-ABL1)-positive chronic myeloid leukemia (CML).
Prescribed by or in consultation with an oncologist or hematologist.
Patient age >= 18 years.
Member has experienced resistance, toxicity, or intolerance to therapy with two or more tyrosine kinase inhibitors (TKIs) (e.g., imatinib, bosutinib, dasatinib, nilotinib, ponatinib).Minimum prior TKIs failed/intolerant = >= 2

Continuation Therapy Criteria

Continued Therapy Criteria

Continued therapy is medically necessary when ALL of the following are met:

CML-specific requirements for continuation

Member is currently receiving medication via Centene benefit, or documentation supports at least 30 days of current Synribo therapy.Minimum prior Synribo exposure for continuation = >= 30 days
Diagnosis: Chronic Myeloid Leukemia.
Member is responding positively to therapy.
New dose does not exceed 2.5 mg per day (1.25 mg subcutaneous twice daily) for 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle.

Other Indications and Exclusions

Diagnoses/Indications NOT authorized

Coverage is NOT authorized for:

Non-FDA approved indications that are not addressed in this policy, unless sufficient documentation of efficacy and safety is provided per off-label use policies (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid).

Applicable Codes

HCPCS - OmacetaxineHCPCSCovered

J9262

Injection, omacetaxine mepesuccinate, 0.01 mg

Provider Actions

Prior Authorization

Documentation required for prior authorization

Provider must submit documentation (office chart notes, lab results, or other clinical information) that demonstrates the member meets all approval criteria, including documentation of prior TKI therapy trials (resistance, toxicity, or intolerance to two or more TKIs) and evidence of response or intolerance to those therapies.

J9262

Documentation Required

Specialist prescribing requirement

Drug must be prescribed by or in consultation with an oncologist or hematologist. If prescribed in consultation, attach consult notes to support the specialist involvement.

Clinical Evidence & References

Primary reference: Synribo Prescribing Information (Teva), 2021; accessed 2025-01-16.

Guideline reference: NCCN Guidelines Chronic Myeloid Leukemia Version 3.2025; accessed 2025-02-11.

Note: These references support the described dose and regimen (induction: 1.25 mg subcutaneous twice daily for 14 consecutive days of a 28-day cycle; maintenance: 1.25 mg subcutaneous twice daily for 7 consecutive days of a 28-day cycle; maximum daily dose 2.5 mg/day).

Background

Omacetaxine (Synribo) is a cephalotaxine ester that inhibits protein synthesis by binding to the A-site in the peptidyl-transferase center of the large ribosomal subunit.

FDA-approved indication: Synribo is indicated for the treatment of adult patients with accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).

Scope/context: This policy defines clinical coverage criteria (initial and continued therapy), dosing limits (maximum 2.5 mg/day; induction 14 consecutive days per 28-day cycle; maintenance 7 consecutive days per 28-day cycle), prior authorization documentation requirements, and coding implications for omacetaxine (Synribo) across Commercial, HIM and Medicaid lines of business.

Definitions

CMLChronic myelogenous leukemia

FDAFood and Drug Administration

Revision History

05.21added

Added requirement that member has experienced resistance, toxicity, or intolerance to two or more TKIs. Added during 2Q2021 annual review; references updated. P&T Approval Date 05.21.

05.22revised

Clarified dosing to allow 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle; maximum dose specified. Clarification made in 2Q2022 annual review; P&T Approval Date 05.22.

05.22added

Policy Summary

PayerHealth Net

PolicyCLINICAL POLICY Omacetaxine

Policy CodePolicy CP.PHAR.108

Change TypeMaterial and administrative updates (2021-2025)

Effective DateApr 1, 2013

Next Review Date

On This Page

Must document prior TKI therapies; added in 2Q2021.

Dose support (choose one)

Prescribed regimen is FDA-approved or recommended by NCCN.
Dose is supported by practice guidelines or peer-reviewed literature for relevant off-label use and prescriber submits supporting evidence.

Dose limits: Dose does not exceed 2.5 mg per day (i.e., 1.25 mg subcutaneous twice daily) for 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle.Maximum daily dose = 2.5 mg/day; Induction = 14 consecutive days per 28-day cycle; Maintenance = 7 consecutive days per 28-day cycle

Dosing clarified in 2Q2022; regimen must follow induction/maintenance pattern.

Maximum daily dose = 2.5 mg/day; Induction = 14 days; Maintenance = 7 days

Dose increase justification (if applicable)

Request for dose increase meets FDA-approved or NCCN-recommended regimen.
New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use and prescriber submits supporting evidence.

Billing Rule

Dose and regimen billing constraint

Ensure billing reflects the approved dosing limits and regimen: maximum dose does not exceed 2.5 mg per day (1.25 mg subcutaneously twice daily) with induction of 14 consecutive days of each 28-day cycle and maintenance of 7 consecutive days of each 28-day cycle.

J9262
Single-use vial availability: 3.5 mg

Prior Authorization

Continued therapy verification

For continuation requests, submit evidence that the member has received at least 30 days of Synribo therapy and documentation that the member is responding positively to therapy.

J9262

05.25removedLatest

Removed off-label use in T315I mutation as this is no longer supported by NCCN Compendium. Removed in 2Q2025 annual review; P&T Approval Date 05.25.

05.23/05.24revisedLatest

Administrative/reference updates. 2Q2023 and 2Q2024 annual reviews noted no significant changes; references reviewed and updated.