Document Number: IC-0156

Last Review Date: 01/05/2023

Date of Origin: 02/07/2013

Dates Reviewed: 11/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 05/2018, 01/2019, 01/2020, 01/2021, 01/2022, 01/2023

1. Length of Authorization

Coverage will be provided for 6 months and may be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

Synribo 3.5 mg for injection single-dose vial:

• Induction: 28 vials every 28 days (until hematologic response is achieved, then begin maintenance)
• Maintenance: 14 vials every 28 days

2. Max Units (per dose and over time) [HCPCS Unit]:

Induction:

• 9,800 billable units every 28 days until hematologic response is achieved, then begin maintenance

Maintenance:

• 4,900 billable units every 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND
• Patient’s disease is confirmed by either a Philadelphia chromosome-positive (Ph+) or BCR::ABL1 positive laboratory test result; AND

Chronic Myeloid Leukemia (CML) † Ф ^1-3

• Used as single agent therapy; AND
• Patient is resistant, intolerant, or had an inadequate response after at least 3 months of therapy with at least TWO tyrosine kinase inhibitor (TKI) therapies (e.g., bosutinib, imatinib, dasatinib, ponatinib, or nilotinib); AND
  • Patient has chronic phase disease; OR
  • Patient has advanced disease that has progressed to accelerated phase; OR
  • Used as post-allogeneic hematopoietic stem cell transplant (HSCT) follow-up therapy in patients with molecular relapse (BCR::ABL1 transcript positive) following complete cytogenetic response (CCyR); OR
  • Used as post-allogeneic HSCT follow-up therapy in patients with relapse or less than CCyR; OR
  • Patient has T315I mutation positive disease

† FDA Approved Indication(s); ‡ Compendia recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1-3

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the indication-specific relevant criteria identified in section III; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: myelosuppression (e.g., severe neutropenia, thrombocytopenia, or anemia), hemorrhage (including cerebral and gastrointestinal), uncontrolled hyperglycemia, etc.; AND
• Treatment response as indicated by one of the following BCR::ABL1 (IS) transcript levels:

• ≤ 10% at 3 months; OR
• ≤ 10% at 6 months; OR
• ≤ 0.1% or a ≥ 3-log reduction in BCR-ABL1 mRNA from the standardized baseline, if qPCR (IS) is not available

Note: cytogenetic assessment of response may be used if quantitative RT-PCR (QPCR) using International Scale (IS) for BCR::ABL1 is not available

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS:

• J9262 – Injection, omacetaxine mepesuccinate, 0.01 mg; 1 billing unit = 0.01 mg

NDC:

• Synribo 3.5 mg single-dose vial for injection: 63459-0177-xx

7. References

1. Synribo [package insert]. North Wales, PA; Teva Pharmaceuticals USA, Inc.; May 2021. Accessed December 2022.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for omacetaxine. National Comprehensive Cancer Network, 2022.  The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed December 2022.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Chronic Myeloid Leukemia 1.2023. National Comprehensive Cancer Network, 2022. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed December 2022.
4. Cortes J, Digumarti R, Parikh M, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. Am J Hematol. 2013 May;88(5):350-4. doi: 10.1002/ajh.23408. Epub 2013 Mar 7.
5. Cortes J, Lipton J, Rea D, et al. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-80.doi: 10.1182/blood-2012-03-415307. Epub 2012 Aug 15.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A