Betibeglogene Autotemcel Form

Betibeglogene autotemcel (Zynteglo®) is an autologous hematopoietic stem cell-based gene therapy. FDA Approved Indication(s)
Zynteglo is indicated for the treatment of adult and pediatric patients with β-thalassemia who require regular red blood cell (RBC) transfusions. 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 Zynteglo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
*Only for initial treatment dose; subsequent doses will not be covered. A. β-Thalassemia (must meet all):

1. Diagnosis of β-thalassemia with genetic confirmation (see Appendix E);
   2. Prescribed by or in consultation with a hematologist and transplant specialist;
   3. Member meets one of the following (a or b): a. Age ≥ 5 years and ≤ 50 years; b. If age < 5 years, member meets both of the following (i and ii): i. Weight ≥ 6 kg; ii. Provider submits medical rationale that member is anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process;
2. Documentation of one of the following (a or b): a. Receipt of ≥ 100 mL/kg packed red blood cells (pRBC) per year for the previous two years (see Appendix D); b. For age ≥ 12 years: Receipt of ≥ 8 transfusions of pRBC per year for the previous two years (see Appendix D);

3. Attestation from transplant specialist for both of the following (a and b): a. Member understands the risks and benefits of alternative therapeutic options such as allogeneic hematopoietic stem cell transplantation (HSCT); b. Member is clinically stable and eligible to undergo myeloablative conditioning and HSCT; Page 1 of 6

   CLINICAL POLICY Betibeglogene Autotemcel

4. Member has not received prior allogeneic HSCT or gene therapy;
   7. Member does not have advanced liver disease (see Appendix D);
   8. Member is not positive for the presence of HIV type 1 or 2;
   9. Member does not have any prior or current malignancy;
   10. Dose contains a minimum of 5 x 106 CD34+ cells/kg.
       Approval duration: 3 months (one time infusion per lifetime)
       B. Other diagnoses/indications (must meet 1 or 2):
5. 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
6. 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. β-Thalassemia
7. Re-authorization is not permitted. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1, 2, or 3):

8. Currently receiving medication via Centene benefit and documentation supports positive response to therapy.
   Approval duration: Duration of request or 6 months (whichever is less); or

   2. 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 Betibeglogene Autotemcel

9. 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 2 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 FDA: Food and Drug Administration HIV: human immunodeficiency virus Appendix B: Therapeutic Alternatives
   Not applicable
   HSCT: hematopoietic stem cell transplantation pRBC: packed red blood cells Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information
   • Conversion of RBC units from mL: 1 RBC unit in these criteria refers to a quantity of pRBC approximately 200-350 mL.
   o For sites who use transfusion bags within this range, or ≥ 350 mL, the conversion in units should be done by dividing the volume transfused to the patient by 350 mL. o For sites who use transfusion bags < 200 mL, the conversion in units should be done by dividing the volume transfused to the patient by 200 mL. • Examples of advanced liver disease include, but are not limited to, the following: o Cirrhosis o Active hepatitis o Bridging fibrosis o Fatty liver disease Appendix E: Genetic Confirmation of β-Thalassemia
   β-Thalassemia Genotype Examples β0/β0 β0/β+ β+ IVS1-110/β+ IVS1-110 ΒE/β0 V. Dosage and Administration
   Indication β-thalassemia
   Dosing Regimen Minimum dose: 5 × 106 CD34+ cells/kg Maximum Dose No maximum dose Page 3 of 6

   CLINICAL POLICY Betibeglogene Autotemcel VI. Product Availability
   Single-dose cell suspension: up to four infusion bags of transduced CD34+ cells in cryopreservation solution labeled for the specific recipient VII.