ModifiedEmblemHealthPolicy MG.MM.PH.368

Zynteglo (betibeglogene autotemcel)

Defines medical necessity criteria, administration, and coding for one-time gene therapy Zynteglo for patients with transfusion-dependent beta‑thalassemia; applies to EmblemHealth/ConnectiCare members and treating providers seeking coverage.

Policy Summary

PayerEmblemHealth

PolicyZynteglo (betibeglogene autotemcel)

Policy CodePolicy MG.MM.PH.368

Change TypeMultiple material and operational revisions

Effective Date

Next Review DateJun 20, 2025

Key ActionSubmit prior authorization with documentation verifying no prior gene therapy and labs within 30 days showing WBC >=3 x10^9/L and platelets >=100 x10^9/L.

SourceLink

POLICY UPDATE CHANGES

Removed criterion requiring verification in claims history that the patient has not received prior gene therapy for beta‑thalassemia.

Added requirement that patient has received or is planning to receive prophylaxis for hepatic veno‑occlusive disease/HSOS before myeloablative conditioning with busulfan.

Updated procedure billing code to J3393 for betibeglogene autotemcel per treatment.

Requirement to avoid myelosuppressive iron chelators for 6 months after infusion of Zynteglo.

Added requirement that the patient has not received a gene therapy for beta-thalassemia in the past and verification in claims history is required; if no claims history, prescribing physician must confirm no prior receipt of Zynteglo or Casgevy.

Updated J-code for administration to J3393.

Added Hepatitis B and Hepatitis C to required negative screening prior to collection of cells for manufacturing.

Removed requirement for avoidance of myelosuppressive iron chelators for 6 months after infusion and removed stated prophylaxis requirement for hepatic VOD before busulfan conditioning.

Replaced wording 'plans to' with 'will' for directive that the patient undergoes mobilization, apheresis, and myeloablative conditioning; and replaced 'recent' with 'within 30 days before intended receipt of Zynteglo' for lab thresholds.

Added current patient body weight to required information.

Changed hematologic requirement from meeting either WBC >=3x10^9/L OR platelets >=100x10^9/L to requiring BOTH thresholds within 30 days before receipt of Zynteglo and absence of hypersplenism.

Added 'significant immunodeficiency disorder' to the list of conditions addressed in prior or current malignancy/myeloproliferative disorder exclusions.

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oneallowed courses per patient

≥5.0e6 CD34+/kgminimum Zynteglo dose

≥12e6 CD34+/kgmobilization/apheresis target

J3393billing code

HBV, HCVrequired infectious screens

claims checkverify no prior gene therapy

Coverage Criteria for Zynteglo (betibeglogene autotemcel)

Initial Therapy (one‑time dose)

Approve for a one‑time (lifetime) dose if the patient meets ALL of the following (A through O):

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Initial Therapy

Covered when ALL of the following are met

Overall coverage prerequisites: Patient has not received a prior gene therapy for beta-thalassemia (verification via claims history or physician attestation if claims are unavailable); patient will undergo mobilization, apheresis, and myeloablative conditioning; negative screening for Hepatitis B and Hepatitis C prior to cell collection; current patient body weight documented; patient does not have significant immunodeficiency disorder or active malignancy/myeloproliferative disorder as specified.see child nodes

Derived from revision history and documentation requirements.

Hematologic and timing criteria: Patient does not have hypersplenism AND within 30 days before intended receipt of Zynteglo has white blood cell count ≥ 3 x 10^9/L AND platelet count ≥ 100 x 10^9/L.WBC >= 3 x10^9/L; Platelets >=100 x10^9/L; timeframe: within 30 days

Stricter requirement changed from OR to AND per revisions.

Coverage is not permitted for concurrent administration of Zynteglo with Reblozyl (luspatercept‑aamt); concurrent use is listed as an exclusion under the policy and will not be authorized. Additionally, patients who have previously undergone a hematopoietic stem cell transplantation are excluded from coverage for Zynteglo. Prior receipt of any gene therapy for beta‑thalassemia (including Zynteglo or other gene therapies) also excludes the patient from receiving another infusion under this policy.

The policy excludes patients with a history of prior or current malignancy or a myeloproliferative disorder, and it now explicitly includes significant immunodeficiency disorders among the comorbidity/exclusion considerations. These conditions should be documented and assessed as part of the preauthorization review; presence of any of these exclusionary conditions will generally render the patient ineligible under the criteria.

Prior hematopoietic stem cell transplantation is a stated exclusion and will render Zynteglo not medically necessary under this policy. Similarly, any documentation or claims evidence of prior gene therapy for beta‑thalassemia (for example, prior administration of Zynteglo or Casgevy) will preclude coverage for a subsequent infusion; the policy requires verification of no prior gene therapy via claims history or physician attestation where claims are unavailable.

This policy specifically excludes patients who have previously received a gene therapy for beta‑thalassemia, including prior treatment with Zynteglo or Casgevy (exagamglogene autotemcel). Verification of absence of prior gene therapy is required during prior authorization—either by claims history or, if claims are unavailable, by the prescribing physician's attestation.

Coding and Dose Information

Applicable CPT/HCPCS CodesHCPCSCovered

J3393

Injection, betibeglogene autotemcel, per treatment

Applicable NDCsNDC

73554-3111-xx

Zynteglo, 20 mL/infusion bag, overwrap, and metal cassette

Applicable ICD-10 DiagnosesICD-10Covered

D56.1

Beta thalassemia

Covered HCPCS CodesHCPCSCovered

J3393

Injection, betibeglogene autotemcel (Zynteglo), per billing update

CD34+ cell dose collection and product dose

Target collection (mobilization/apheresis)Collect ≥ 12 ×10^6 CD34+ cells/kg

Minimum product dose (single IV infusion)Product contains a minimum of 5.0 ×10^6 CD34+ cells/kg of body weight

If minimum not metAdditional cycles of mobilization and apheresis separated by ≥14 days may be performed; up to two drug product lots may be administered to meet target dose

Hematologic thresholds before infusion

White blood cell (WBC) thresholdWBC ≥ 3 × 10^9/L measured within 30 days before intended receipt of Zynteglo

Platelet threshold

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for a one-time, lifetime administration of Zynteglo (HCPCS J3393). Coverage is limited to one dose and will not be renewed.

HCPCS J3393 — Injection, betibeglogene autotemcel, per treatment
One-time (lifetime) dose coverage only
Prior authorization required before administration

Documentation Required

Documentation Submission Required

The treating physician must submit clinical evidence that the member meets all policy criteria for treatment to EmblemHealth (or ConnectiCare as applicable). Failure to submit required documentation will prevent proper preauthorization review or post-payment review.

Submit full clinical documentation demonstrating all policy criteria are met

Background

Zynteglo is an autologous hematopoietic stem cell‑based gene therapy indicated for treatment of beta‑thalassemia in patients who require regular red blood cell transfusions. Treatment consists of mobilization and apheresis to collect CD34+ cells, ex vivo gene modification of the patient’s hematopoietic stem cells, full myeloablative conditioning (commonly with busulfan), and a single intravenous infusion of the modified product. Coverage under this policy is limited to a one‑time (lifetime) dose per patient.

Definitions and Key Terms

Zynteglo (definition)

DefinitionAutologous hematopoietic stem cell–based gene therapy indicated for treatment of beta‑thalassemia in patients who require regular red blood cell (RBC) transfusions

Product typeSingle intravenous infusion following HSC mobilization, apheresis, ex vivo gene modification, and myeloablative conditioning

Indication populationAdults and pediatric patients with transfusion‑dependent beta‑thalassemia

Backup collection (definition and thresholds)

Backup collection definitionCryopreserved backup collection of patient cells prior to myeloablative conditioning

Apheresis threshold≥ 1.5 × 10^6 CD34+ cells/kg collected by apheresis

Policy Summary

PayerEmblemHealth

PolicyZynteglo (betibeglogene autotemcel)

Policy CodePolicy MG.MM.PH.368

Change TypeMultiple material and operational revisions

Effective Date

Next Review DateJun 20, 2025

Key ActionSubmit prior authorization with documentation verifying no prior gene therapy and labs within 30 days showing WBC >=3 x10^9/L and platelets >=100 x10^9/L.

SourceLink

On This Page

Platelet count ≥ 100 × 10^9/L measured within 30 days before intended receipt of Zynteglo

Timing and hypersplenismBoth hematologic thresholds must be met within 30 days before intended receipt and patient must not have hypersplenism

If documentation is not provided, preauthorization or post-payment review cannot be completed

Prior Authorization

Clinical Evidence for Medical Necessity

Clinical evidence submitted with the prior authorization must demonstrate medical necessity and that the member meets all specific eligibility criteria in the policy (including age, transfusion dependence, genotype confirmation, infection status, appropriateness for hematopoietic stem cell transplantation, and required treatment steps). If claims history does not verify prior therapy status, a physician attestation is required to confirm no prior gene therapy for beta-thalassemia.

Provide documentation of age, transfusion history, genotype (DNA analysis), infection screening, and treating physician assessment that HSCT is appropriate
Include evidence that patient will undergo mobilization, apheresis, and myeloablative conditioning
If claims do not show prior gene therapy status, include prescribing physician attestation of no prior gene therapy for beta-thalassemia

Denial Risk

Concurrent Therapy Exclusion

Concurrent use with Reblozyl (luspatercept‑aamt) is excluded and will not be authorized.

Do not authorize Zynteglo if the member is receiving Reblozyl concurrently

Documentation Required

Prior Authorization Requirements and Required Documentation

Prior authorization review must include verification that the member has not previously received a gene therapy for beta-thalassemia. Verification may be done via claims history; if claims are unavailable or show no prior therapy, include a prescribing physician attestation confirming no prior receipt of Zynteglo or Casgevy. Documentation must also include current patient body weight and laboratory values (including WBC and platelet counts) obtained within 30 days before the intended receipt of Zynteglo, and negative Hepatitis B and C screening prior to collection of cells for manufacturing.

Verify no prior gene therapy for beta-thalassemia via claims history; if none or claims unavailable, include physician attestation
Include current patient body weight
Include laboratory values (WBC, platelet counts, hemoglobin as required) within 30 days before intended receipt of Zynteglo
Provide negative Hepatitis B and Hepatitis C screening results prior to cell collection

Bone marrow threshold> 1.0 × 10^8 Total Nucleated Cells (TNC)/kg if collected by bone marrow harvest

Timing for laboratory thresholds

Defined timing windowLaboratory values must be obtained within 30 days before intended receipt of Zynteglo

Applies to hematologic thresholdsWBC and platelet counts referenced in policy must be measured in this timeframe

Documentation requirementCurrent patient body weight and labs within this 30‑day window must be included in prior authorization documentation