ModifiedmhnPolicy CP.PHAR.108

Omacetaxine (Synribo)

Covers medical necessity and prior authorization criteria for omacetaxine (Synribo) for treatment of chronic myeloid leukemia (CML) and guidance for other indications and continued therapy for members of the payer lines of business.

Policy Summary

Payermhn

PolicyOmacetaxine (Synribo)

Policy CodePolicy CP.PHAR.108

Change TypeMaterial updates (removed unsupported off‑label useclarified dosingadded prior TKI requirement)

Effective DateApr 1, 2013

Next Review Date

Key ActionPrior authorization required with supporting documentation; provider must document resistance, toxicity, or intolerance to two or more TKIs.

SourceLink

POLICY UPDATE CHANGES

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

Clarified dosing to include allowance for dosing 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle and maximum daily dose.

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

2.5 mg/m2/dayMaximum daily dose

14d induction / 7d maintenanceDosing schedule

Age ≥ 18Minimum age

≥2 TKIsPrior therapy

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Coverage Criteria

Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met:

Initial CML criteria: 1. Diagnosis of Ph+ (BCR-ABL1-positive) chronic myeloid leukemia (CML). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Age ≥ 18 years. 4. Member has experienced resistance, toxicity, or intolerance to prior therapy with two or more tyrosine kinase inhibitors (e.g., imatinib, bosutinib, dasatinib, nilotinib, ponatinib). 5. Request meets one of the following: a) Dose does not exceed 2.5 mg/m2 per day for 14 consecutive days for induction and 7 consecutive days for maintenance of each 28-day cycle; OR b) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use with supporting evidence submitted by the prescriber. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM 6 months; Commercial 6 months or to the member's renewal date.

Continuation Therapy — Covered for continuation when ALL of the following are met

Covered for continuation when ALL of the following are met:

Continued therapy CML: 1. Member is currently receiving Synribo via the Centene benefit, or documentation supports the member has received Synribo for CML for at least 30 days. 2. Member is responding positively to therapy. 3. If the request is for a dose increase, the request meets one of the following: a) New dose does not exceed 2.5 mg/m2 per day for 14 consecutive days induction and 7 consecutive days maintenance of each 28-day cycle; OR b) New dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use with supporting evidence submitted by the prescriber. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: Medicaid/HIM 12 months; Commercial 6 months or to the member's renewal date.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or unless coverage is established in the member's evidence of coverage document.

When coverage provisions in this clinical policy conflict with applicable state Medicaid coverage rules, the state Medicaid coverage provisions take precedence. Providers and reviewers should consult the relevant state Medicaid manual for any state‑specific coverage guidance.

Requests for therapy for non‑FDA approved indications that lack sufficient documentation or endorsement per the payer's off‑label use policies are considered not authorized and will be denied unless the prescriber submits acceptable supporting evidence as described in those off‑label policies.

Regimen	Dose	Schedule	Maximum daily dose
Induction
1.25 mg/m2 subcutaneous twice daily
14 consecutive days of a 28-day cycle
2.5 mg/m2 per day

Coding

HCPCS CodesHCPCS

J9262

Injection, omacetaxine mepesuccinate, 0.01 mg

inv-07: Maximum Dose — 2.5 mg/m2 per day

Maximum daily dose2.5 mg/m2 per day

Induction daily total1.25 mg/m2 twice daily (total 2.5 mg/m2) during induction days

Maintenance daily total1.25 mg/m2 twice daily (total 2.5 mg/m2) during maintenance days

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Requests must include supporting documentation demonstrating that the member meets all applicable clinical criteria (see Clinical Criteria). Providers must submit office chart notes, relevant laboratory results, and any other clinical information necessary to support that the member has met the approval requirements.

Prior authorization required with supporting documentation.
HCPCS code J9262 corresponds to omacetaxine mepesuccinate.

Step Therapy

Prior TKI Requirement

Member must have experienced resistance, toxicity, or intolerance to prior therapy with two or more tyrosine kinase inhibitors (TKIs) (e.g., imatinib, bosutinib, dasatinib, nilotinib, ponatinib) prior to approval. For specific mutations (e.g., T315I), prior treatment requirements may differ per clinical criteria and guideline-referenced exceptions.

Background

Omacetaxine (a cephalotaxine ester) inhibits protein synthesis by binding the ribosomal peptidyl‑transferase center, thereby disrupting elongation of nascent polypeptides. The agent is FDA‑approved for treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) who have resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).

Definitions and Key Terms

inv-17: Dosing regimen — Induction and maintenance dosing specifics

Induction regimen1.25 mg/m2 subcutaneous twice daily for 14 consecutive days of a 28-day cycle

Maintenance regimen1.25 mg/m2 subcutaneous twice daily for 7 consecutive days of a 28-day cycle

Cycle lengthEach regimen is described per 28-day cycle (induction = 14 days on, maintenance = 7 days on)

Maximum daily doseDose must not exceed 2.5 mg/m2 per day for the 14/7 schedule

inv-18: Ph+ CML — Definition of Philadelphia chromosome (BCR-ABL1) positive CML

DefinitionPh+ (BCR-ABL1-positive) CML: chronic myeloid leukemia positive for the Philadelphia chromosome (BCR-ABL1)

Line of Therapy

salvage — salvage therapy node

Salvage (line of therapy): Used for CML patients with resistance and/or intolerance to two or more TKIs; considered after multiple TKI failures; must be prescribed by or in consultation with an oncologist or hematologist.

Biomarker Requirements

inv-21: BCR-ABL1 (Ph+) — biomarker requirement for coverage

Required biomarkerBCR-ABL1 (Philadelphia chromosome) positivity is required to confirm CML diagnosis for coverage

PurposeMarker required for diagnosis confirmation of Ph+ CML prior to approval

Link to indicationSynribo indicated for adult patients with chronic or accelerated phase CML with resistance/intolerance to ≥2 TKIs — BCR-ABL1 positivity defines Ph+ disease

Covered Regimens

Indication	Dose and route	Administration schedule	Maximum daily dose
Chronic myeloid leukemia (chronic or accelerated phase)
1.25 mg/m2 subcutaneous, twice daily
Induction: 14 consecutive days of a 28-day cycle; Maintenance: 7 consecutive days of a 28-day cycle
2.5 mg/m2 per day