Betibeglogene autotemcel (Zynteglo) — Coverage Criteria for Transfusion-Dependent Beta-Thalassemia
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Defines medical necessity, eligibility criteria, and authorization details for coverage of betibeglogene autotemcel (Zynteglo) intravenous infusion for members with transfusion-dependent beta-thalassemia in North Carolina.
Added requirement to discontinue any disease-modifying therapies for TDT (e.g., mitapivat) prior to planned HSC mobilization and myeloablative conditioning.
Added requirement that patient has no available willing and healthy 10/10 HLA-matched related hematopoietic-cell donor.
Added applicable revenue codes 0891 and 0892 associated with policy HCPCS code(s).
Medical Necessity and Eligibility Criteria
Medical necessity - eligibility criteria
Covered when ALL of the following are met:
medical record documentation required
Age-based cohort and transfusion history
- Pediatrics (<12): If <5 years: weight ≥6 kg AND prescriber documents ability to provide minimum number of cells; AND documented transfusion history: ≥100 mL/kg/year of pRBCs OR ≥8 pRBC transfusions in prior 12 months
medical record documentation required
- Adolescents/Adults (12–50): Documented transfusion history: ≥100 mL/kg/year of pRBCs OR ≥8 pRBC transfusions in prior 12 months; AND clinically stable and able to undergo HSCT; AND candidate for allogeneic HCT but NO available willing and healthy 10/10 HLA-matched related donor
medical record documentation required
medical record documentation required
medical record documentation required
medical record documentation required
medical record documentation required
In addition to the core eligibility criteria, the policy specifies several exclusions and clinical considerations that must be documented in the medical record. Prior gene therapy for the requested diagnosis disqualifies the member from coverage for this therapy. Patients with advanced liver dysfunction (ALT, bilirubin, or alkaline phosphatase ≥ 3x ULN, or INR ≥ 1.4), active infections, HIV positivity, or other conditions the treating provider judges as severe iron overload that would warrant exclusion are not eligible. Specific infection and serology requirements include acceptable hepatitis B and C testing results and no other active infections. These exclusions and required laboratory/imaging assessments must be clearly documented to support medical necessity.
Any request that does not meet ALL of the listed medical necessity criteria is considered not medically necessary and will not be covered. This includes failure to document the transfusion history thresholds (≥100 mL/kg/year pRBC or ≥8 pRBC transfusions in the prior 12 months where applicable), absence of required laboratory or imaging results (e.g., WBC ≥3 x 10^9/L, platelets ≥100 x 10^9/L, cardiac T2* ≥10 ms, liver tests within specified limits), lack of documentation regarding donor availability (no willing healthy 10/10 HLA-matched related donor when required), or missing evidence of planned mobilization and conditioning or discontinuation of disease‑modifying therapies. Requests with these documentation deficiencies may be denied.
Billing Codes, Clinical Thresholds, and Key Values
| J3393 | betibeglogene autotemcel (Zynteglo) intravenous infusion |
| 0891 | Special Processed Drugs - FDA Approved Cell Therapy (revenue) |
| 0892 | Special Processed Drugs - FDA Approved Gene Therapy (revenue) |
Prior Authorization, Documentation, and Billing Instructions
Prior Authorization Required
Prior authorization is required for betibeglogene autotemcel (Zynteglo) prior to administration. Use HCPCS code J3393. Maximum units = 1 (single-dose, single-course per lifetime). Distribution from a specialty pharmacy provider may be required (distribution channel restriction) — contact Blue Cross NC to coordinate.
- HCPCS: J3393
- Maximum units: 1 (single-dose)
- Distribution channel restriction: specialty pharmacy/provider coordination may be required
Step Therapy
No step therapy requirements are specified for this gene therapy product.
Required Medical Record Documentation
Medical record documentation must include: diagnosis of transfusion-dependent beta‑thalassemia (β‑thalassemia major/TDT); detailed transfusion history (e.g., ≥100 mL/kg/year pRBC or ≥8 pRBC transfusions in prior 12 months); labs and imaging supporting eligibility (CBC with WBC and platelet counts, liver enzymes, bilirubin, INR, cardiac T2* MRI), hepatitis B/C testing results, HIV status, iron overload assessment, and documentation of candidacy/absence of 10/10 HLA‑matched related donor. Also document planned mobilization (G‑CSF and plerixafor), full myeloablative conditioning with busulfan, discontinuation of disease‑modifying therapies prior to mobilization, and that the requested dose is within FDA‑labeled dosing.
- Diagnosis documentation: transfusion‑dependent beta‑thalassemia (TDT)
- Transfusion history: ≥100 mL/kg/year pRBC OR ≥8 pRBC transfusions in prior 12 months
- CBC with WBC and platelet counts
- Liver tests: ALT, bilirubin, alkaline phosphatase, INR
- Cardiac MRI T2* result
- Hepatitis B and C serologies and HBV DNA/HCV RNA as applicable
- HIV status
- Documentation of no active infection or uncorrected bleeding disorder
- Documentation of mobilization plan (G‑CSF + plerixafor) and myeloablative conditioning (busulfan)
- Documentation patient is candidate for HSCT and lacks available 10/10 HLA‑matched related donor
- If prior gene therapy: documentation that none received
Documentation Deficiencies That May Trigger Denial
Missing or incomplete documentation may result in denial of the request. Common deficiencies that can trigger denial include absent or insufficient transfusion history, missing lab or imaging results (e.g., cardiac T2*, liver tests, CBC), lack of documentation regarding donor availability or HSCT candidacy, failure to document planned conditioning and mobilization, or absence of hepatitis/HIV test results.
- Absent transfusion history or insufficient detail
- Missing CBC, platelet, liver panel, INR, or cardiac T2* MRI
- No documentation of lack of 10/10 HLA‑matched related donor or HSCT candidacy
- No plan or documentation for G‑CSF/plerixafor mobilization and busulfan conditioning
- No documentation of discontinuation of disease‑modifying therapies prior to mobilization
Therapy Background
Betibeglogene autotemcel (Zynteglo) is a CD34+ stem cell–based gene therapy administered as a single-course, one-time treatment to members with transfusion-dependent beta-thalassemia (TDT). Treatment involves mobilization of hematopoietic stem cells with G-CSF and plerixafor, collection and infusion of autologous CD34+ cells, and full myeloablative conditioning with busulfan prior to infusion. Extensive eligibility screening and documentation are required because the therapy is a one-time, high-cost intervention with specific laboratory, imaging, infectious disease, donor-availability, and prior-therapy exclusions.
Key Definitions
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