SYNRIBO, Omacetaxine Mepesuccinate Form

Omacetaxine (Synribo®) is 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(s) Synribo is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Synribo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Myeloid Leukemia (must meet all):

1. Diagnosis of Ph+ (BCR-ABL1-positive) CML;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Request meets one of the following (a or b): a. Member has experienced resistance, toxicity, or intolerance to prior therapy with two or more TKIs (e.g., imatinib, Bosulif®, Sprycel®, Tasigna®, Iclusig®); b. Member has T315I mutation and has received prior treatment with Iclusig and Scemblix®;

2. Request meets one of the following (a or b): 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. b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). 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, whichever is longer Page 1 of 6

   CLINICAL POLICY Omacetaxine B. Other diagnoses/indications (must meet 1 or 2):

3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Chronic Myeloid Leukemia (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Synribo for CML and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. If request is for a dose increase, request meets one of the following (a or b): a. New 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; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). 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, whichever is longer B. Other diagnoses/indications (must meet 1 or 2):

7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY Omacetaxine

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CML: chronic myelogenous leukemia FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose Adult: 800 mg/day 600 mg/day Adults: 180 mg/day Adults: 600 mg/day 45 mg/day 200 mg/day imatinib
   (Gleevec®)
   Bosulif®
   (bosutinib) Sprycel®
   (dasatinib)
   Tasigna®
   (nilotinib)
   Iclusig®
   (ponatinib) Scemblix® (asciminib) Adult: • 400-600 mg/day PO for chronic phase • 600-800 mg/day PO for accelerated phase or blast crisis (800 mg given as 400 BID)
   400 mg PO QD Adults: • Chronic phase: 100-140 mg/day PO • Accelerated, myeloid phase, or lymphoid blast phase: 140-180 mg/day PO
   Adults: 300 mg PO BID Starting dose 45 mg PO QD 200 mg PO BID Appendix C: Contraindications/Boxed Warnings None reported Page 3 of 6

   CLINICAL POLICY Omacetaxine V. Dosage and Administration
   Indication Dosing Regimen CML Induction dose: 1.25 mg/m2 subcutaneous twice daily for 14 consecutive days of a 28-day cycle Maintenance dose: 1.25 mg/m2 subcutaneous twice daily for 7 consecutive days of a 28-day cycle Maximum Dose 2.5 mg/m2 per day VI. Product Availability
   Single-use vial: 3.5 mg of omacetaxine mepesuccinate as a lyophilized powder VII.