ModifiedCentenePolicy CP.PHAR.545

Clinical Policy: Betibeglogene Autotemcel (Zynteglo)

Criteria and administrative requirements for coverage of a single-dose autologous hematopoietic stem cell-based gene therapy (Zynteglo) for patients with transfusion-dependent β-thalassemia; applies to Centene-affiliated health plans and providers requesting authorization. PDAC review is required for all requests.

Policy Summary

PayerCentene

PolicyBetibeglogene Autotemcel (Zynteglo) coverage criteria

Policy CodePolicy CP.PHAR.545

Change TypeMaterial revisions and coding updates

Effective DateNov 1, 2022

Next Review Date

Key ActionSubmit prior authorization requests with transplant specialist attestation, recent negative HIV test (within 6 months), body weight for dosing, transfusion history, and supporting clinical documentation for PDAC review.

SourceLink

POLICY UPDATE CHANGES

Criteria updated per FDA labeling to add transplant specialist involvement, clarify transfusion-dependence options, revise HSCT eligibility attestation, remove hepatitis B/C exclusion, and set minimum dose.

Revised lower age limit to age ≥ 4 years and removed accompanying age < 5 criteria; removed age qualifier of ≥ 12 years for receipt of ≥ 8 transfusions of pRBC per year.

Approval duration extended from 3 months to 6 months to allow for member preparation and adequate time for gene therapy manufacture.

Added HCPCS code J3393 and removed HCPCS codes J3590 and C9399.

Added transplant specialist involvement requirement and clarified multidisciplinary team involvement per FDA labeling.

Added requirement for documentation of member's body weight for verification of weight-based dose.

Redirected prior authorization reviews to Precision Drug Action Committee (PDAC) Utilization Management Review.

Added clarification for time component and documentation within the last 6 months for negative HIV test.

Added clarification that therapy is a one-time dose only for continued authorization.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

one-timeinfusion per lifetime

4–50approved patient age range

≥5×10^6 CD34+/kgminimum dose

≥100 mL/kg or ≥8transfusion requirement

6 monthsauthorization period

J3393HCPCS code

Coverage Criteria

Initial Therapy (β-thalassemia)

Covered when ALL of the following are met

Initial Approval - B-thalassemia: 1) Diagnosis of β-thalassemia with genetic confirmation (see Appendix E); 2) Prescribed by or in consultation with a hematologist and transplant specialist; 3) Age ≥ 4 years and ≤ 50 years; 4) Documentation of ONE of the following measured per year for the previous two years: (a) receipt of ≥ 100 mL/kg packed red blood cells (pRBC) per year OR (b) receipt of ≥ 8 transfusions of pRBC per year; 5) Attestation from a transplant specialist that: (a) the member understands the risks and benefits of alternative therapeutic options such as hematopoietic stem cell transplantation (HSCT), and (b) the member is clinically stable and eligible to undergo myeloablative conditioning and HSCT; 6) Member has not received prior allogeneic HSCT; 7) Member has not received prior gene therapy; 8) Member does not have advanced liver disease; 9) Documentation within the last 6 months that the member is negative for HIV-1/2; 10) Member does not have any prior or current malignancy; 11) Documentation of member's body weight in kg; 12) Dose contains a minimum of 5 x 10^6 CD34+ cells/kg.see nodes

Approval duration: 6 months (one-time infusion per lifetime)

Initial therapy (summary)

Covered when ALL of the following are met (summary from document updates):

Eligibility summary: Member meets revised minimum age (≥ 4 years); meets transfusion‑dependence criteria per policy (either ≥ 100 mL/kg pRBC/year or ≥ 8 transfusions/year measured per year for the prior two years); transplant specialist involvement and attestation documented that member understands alternative options (e.g., HSCT) and is clinically stable; required testing documented including negative HIV within the last 6 months; body weight documented for weight‑based dosing; therapy is administered as a one‑time dose; minimum cellular dose ≥ 5 x 10^6 CD34+ cells/kg; prior allogeneic HSCT or prior gene therapy absent; no advanced liver disease or active malignancy.see individual criteria in full policy

Approval duration: 6 months (one-time administration)

Coverage is limited to FDA-approved indications. Non‑FDA approved indications are not authorized unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for the marketplace, CP.PMN.53 for Medicaid) or evidence of coverage documents demonstrating medical necessity.

Per the FDA labeling updates incorporated into this policy, exclusion criteria for hepatitis B and hepatitis C viruses have been removed and are no longer listed as disqualifying conditions.

Zynteglo is authorized as a single course therapy. Therapy is one‑time only and continued maintenance dosing is not covered; approval is granted to support the single administration and associated preparation activities.

Repeated administration beyond the single, one‑time infusion is not permitted. No additional or subsequent administrations are authorized (continued authorization is limited to the one‑time dose as specified in this policy).

Initial Therapy Criteria (Drug-Specific)

Initial Therapy (drug-specific)

Initial treatment dose — one-time infusion only; all criteria must be met.

Drug-specific initial criteria: 1) Indication: transfusion‑dependent β‑thalassemia with genetic confirmation (Appendix E); 2) Prescribed by or in consultation with a hematologist and transplant specialist; 3) Age ≥ 4 and ≤ 50 years; 4) Transfusion history: either ≥ 100 mL/kg pRBC/year OR ≥ 8 transfusions/year for each of the previous 2 years (measured per year); 5) Transplant specialist attestation that member understands risks/benefits of alternatives (including HSCT) and is clinically stable and eligible for myeloablative conditioning; 6) No prior allogeneic HSCT; 7) No prior gene therapy; 8) No advanced liver disease; 9) HIV‑1/2 negative within last 6 months; 10) No prior or current malignancy; 11) Body weight documented in kg for dose verification; 12) Dose contains minimum of 5 x 10^6 CD34+ cells/kg; 13) Quantity limit: up to four infusion bags (single‑dose cell suspension) labeled for the recipient; administered as a one‑time course per lifetime.

Initial therapy (summary)

Initial authorization requirements (summarized):

Initial authorization summary: Member meets age criteria (≥ 4 years); transfusion‑dependence criteria met per policy (≥ 100 mL/kg pRBC/year or ≥ 8 transfusions/year measured per year for prior two years); transplant specialist involvement and attestation provided; required testing documented including negative HIV within last 6 months; member body weight documented for weight‑based dosing; HCPCS J3393 to be billed for the one‑time treatment; therapy is a single administration (one‑time dose).

Continuation / Maintenance Criteria

Continuation Therapy

Continuation/maintenance therapy policy

Continuation Therapy: Not applicable for ongoing dosing: Zynteglo (betibeglogene autotemcel) is indicated as a one‑time administration and continued/maintenance therapy will not be authorized.

Continuation therapy

Continued authorization rules

Continued authorization: Only a single‑administration (one‑time) dose is allowed; repeated administration beyond the one‑time dose is not authorized. Approval duration for the initial/only administration may be granted for up to 6 months to accommodate preparation and manufacture.one-time

Medical director review template and continued therapy template adjusted elsewhere in policy.

Coding and Dose Thresholds

HCPCS Codes referencedHCPCS

J3393

Injection, betibeglogene autotemcel, per treatment

Referenced HCPCS CodesHCPCS

J3393	Injection, betibeglogene autotemcel, per treatment
J3590	Removed (previously used HCPCS code)
C9399	Removed (previously used HCPCS code)

inv-09: Minimum CD34+ cell dose

Minimum CD34+ cell dose≥ 5 x 10^6 CD34+ cells/kg

Source sectionV. Dosage and Administration - minimum dose for β-thalassemia

Policy noteDose requirement confirmed in initial approval criteria and dosing appendix

inv-10: Transfusion-dependence threshold

Transfusion-dependence thresholdReceipt of ≥ 100 mL/kg pRBC per year for each of the previous two years

Alternative thresholdReceipt of ≥ 8 transfusions of pRBC per year for each of the previous two years

Provider Actions, Documentation & Review Routing

Prior Authorization

Prior Authorization and PDAC Review Required

Prior authorization and PDAC review are required for all requests. Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member meets all approval criteria. All requests reviewed under this policy require Precision Drug Action Committee (PDAC) Utilization Management Review. Refer to CC.PHAR.21 for process details.

Prior authorization (PA) required for betibeglogene autotemcel
All PA requests will be routed to PDAC Utilization Management Review
Refer to CC.PHAR.21 for PDAC submission process

Note

Prior Authorization Routing to PDAC Utilization Management Review

PA routing has been updated to route prior authorization reviews to the PDAC Utilization Management Review for operational review and determination. Ensure submissions follow the PDAC routing process and include all required documentation to avoid routing delays.

Operational routing: PA -> PDAC Utilization Management Review

Step Therapy and Attestation

Requirement	Detail
Transplant specialist attestation that member understands risks and benefits of alternative therapeutic options (e.g., HSCT)	Attestation from the transplant specialist that the member understands the risks and benefits of alternative therapeutic options such as hematopoietic stem cell transplantation (HSCT).
Transplant specialist attestation of clinical stability and HSCT eligibility	Attestation that the member is clinically stable and eligible to undergo myeloablative conditioning and HSCT.
Prescriber involvement	Prescribed by or in consultation with a hematologist and transplant specialist.

Documentation Element	Required Content / Evidence
Discussion of alternative therapeutic options	Documentation that alternatives (including allogeneic HSCT) were discussed with the member, as attested by the transplant specialist.
Transplant specialist eligibility attestation	Transplant specialist attestation that the member is clinically stable and eligible to undergo myeloablative conditioning and HSCT.
Prescriber specialty involvement	Evidence that the request was prescribed by or in consultation with a hematologist and transplant specialist.

Quantity Limits

inv-30: Betibeglogene autotemcel (Zynteglo)

Quantity limitUp to four infusion bags of transduced CD34+ cells in cryopreservation solution labeled for the specific recipient

Product formSingle-dose cell suspension (cryopreserved)

Per-policy contextDefined under Product Availability for betibeglogene autotemcel (Zynteglo)

inv-31: betibeglogene autotemcel

Administration frequencyOne-time administration (single-dose) — quantity limit: one-time

Continuation policyContinued therapy will not be authorized; repeated administrations are not covered

Authorization implication

Site of Care Requirements

Note

Hospital outpatient: multidisciplinary team and single‑dose cell suspension

Administration must occur in a hospital outpatient setting with a multidisciplinary team that includes hematology and transplant specialists; the product is provided as a single‑dose cell suspension (up to four infusion bags) labeled for the recipient.

Product format: single‑dose cell suspension (up to four infusion bags) of transduced CD34+ cells labeled for the recipient.
Site of care requires multidisciplinary team including hematology and transplant specialists.

Note

Transplant specialist required for hospital outpatient administration

Transplant specialist involvement is required for site-of-care planning and authorization; the policy reiterates that multidisciplinary and transplant specialist participation is needed though exact site specifics are not further detailed in this excerpt.

Prescribing must be by or in consultation with a hematologist and transplant specialist.
Policy emphasizes transplant specialist role but does not specify additional site requirements in the provided text.

Definitions and Supporting Terms

inv-21: pRBC definition

pRBC unit volumeApproximately 200–350 mL per pRBC unit

Conversion guidance (≥350 mL)For sites using transfusion bags ≥350 mL, divide transfused volume by 350 mL to convert to units

Conversion guidance (<200 mL)For sites using transfusion bags <200 mL, divide transfused volume by 200 mL to convert to units

inv-22: HSCT / transplant specialist attestation definition

HSCT definitionHSCT = hematopoietic stem cell transplantation; involves myeloablative conditioning as applicable

Attestation requirementTransplant specialist must attest that the member understands risks and benefits of alternative therapeutic options (including HSCT) and is clinically stable and eligible for myeloablative conditioning

Background

Background: Betibeglogene autotemcel (Zynteglo) is an autologous hematopoietic stem cell–based gene therapy indicated for patients with transfusion‑dependent β‑thalassemia. The product is manufactured ex vivo from the patient’s CD34+ hematopoietic stem/progenitor cells, formulated as a single‑dose cell suspension (up to four infusion bags labeled for the recipient), and administered as a single infusion following myeloablative conditioning. Clinical eligibility requires genetic confirmation of β‑thalassemia and other criteria (age, transfusion history, transplant specialist involvement, negative HIV within 6 months, minimum CD34+ cell dose, and absence of disqualifying comorbidities) as detailed in the coverage criteria; prior authorization and Precision Drug Action Committee (PDAC) review are required for all requests.

Policy Summary

PayerCentene

PolicyBetibeglogene Autotemcel (Zynteglo) coverage criteria

Policy CodePolicy CP.PHAR.545

Change TypeMaterial revisions and coding updates

Effective DateNov 1, 2022

Next Review Date

SourceLink

On This Page

per policy and FDA labeling

Approval duration: 6 months to allow for member preparation and product manufacture.

Conversion guidanceAppendix D: 1 RBC unit ≈ 200–350 mL; convert volumes by dividing transfused mL by 350 mL (or 200 mL if <200 mL bags)

inv-11: Authorization duration

Authorization duration (initial approval)6 months (to allow member preparation and time for gene therapy manufacture)

One-time infusion noteTherapy is a one-time infusion per lifetime; approval covers preparation/manufacture period

Policy changeExtended from 3 months to 6 months per 3Q 2024 annual review

Include all required documentation with initial PA submission to prevent return for missing information

Step Therapy

Step Therapy / Alternatives

No formal step therapy is required; however, a transplant specialist attestation is mandatory. The transplant specialist must document that alternative therapeutic options, including allogeneic hematopoietic stem cell transplantation (HSCT), have been discussed and that the member understands risks and benefits.

No step therapy required
Transplant specialist attestation required regarding discussion of alternatives (e.g., HSCT)

Documentation Required

Multidisciplinary Evaluation Requirement

A multidisciplinary evaluation is required. Prescriptions must be by or in consultation with a hematologist and a transplant specialist, and documentation must show transplant specialist involvement and that alternatives such as HSCT were discussed and considered.

Prescribed by or in consultation with a hematologist and transplant specialist
Documentation must show transplant specialist involvement and discussion of HSCT alternatives

Documentation Required

Required Documentation for Initial Prior Authorization

Submit all required documentation with the initial prior authorization request. Incomplete submissions may delay review or result in denial. Required documents include genetic confirmation, transfusion history, transplant specialist attestation, and recent HIV testing.

Office chart notes and consultation notes (including hematologist and transplant specialist documentation)
Genetic confirmation of β-thalassemia (see Appendix E)
Transfusion history documenting either ≥100 mL/kg pRBC per year for the previous two years OR ≥8 pRBC transfusions per year for the previous two years (see Appendix D)
Transplant specialist attestation that the member understands risks/benefits of alternatives (e.g., HSCT) and is clinically stable and eligible for myeloablative conditioning and HSCT
Documentation the member has not had prior allogeneic HSCT or prior gene therapy
Documentation within the last 6 months of negative HIV-1/2 test
Documentation that member does not have prior or current malignancy
Member body weight in kg for dose verification
Planned dose confirmation that dose contains minimum 5 x 10^6 CD34+ cells/kg

Documentation Required

Required Documentation for Prior Authorization

For prior authorization, include the transplant specialist attestation and documentation of clinical stability and eligibility. Failure to include these materials may result in incomplete review or denial.

Transplant specialist attestation (see required elements above)
Clinical notes confirming member is clinically stable and eligible for myeloablative conditioning and HSCT
Recent labs and test results referenced in criteria (e.g., HIV test within 6 months)
Weight documentation for dosing

Denial Risk

Documentation Insufficiency May Trigger Denial

Documentation insufficiency may trigger denial. If required documents are missing or incomplete, the request may be denied rather than routed for additional review.

Missing genetic confirmation, transfusion history, or transplant specialist attestation may lead to denial
Absent HIV test within the last 6 months may trigger denial
No documentation of body weight (kg) for dose verification may trigger denial

Denial Risk

Documentation-Related Denials

Specific documentation-related denials: denials may be issued when essential attestations or tests are not provided. Ensure all listed elements are included in the initial submission to avoid denial.

Denial triggers: missing transplant specialist attestation regarding alternatives and clinical stability
Denial triggers: no HIV-1/2 test result within last 6 months
Denial triggers: missing transfusion history demonstrating transfusion dependence per criteria
Denial triggers: missing body weight in kg for dose calculation
Denial triggers: evidence of prior allogeneic HSCT or prior gene therapy when criteria exclude such history

Authorization templates and duration reflect single administration policy

Provider involvementTherapy must be prescribed by or in consultation with a hematologist and transplant specialist

inv-23: Transplant specialist attestation

Attestation wordingTransplant specialist attestation that: (a) member understands risks and benefits of alternative therapeutic options such as HSCT; and (b) member is clinically stable and eligible to undergo myeloablative conditioning and HSCT

Intent of attestationDocuments that alternatives were discussed and confirms clinical stability and eligibility for conditioning required for gene therapy

Documentation placementAttestation is required as part of prior authorization submission and PDAC review