ModifiedCentenePolicy CP PHAR.545

Betibeglogene Autotemcel (Zynteglo)

Coverage policy governing one-time administration of Zynteglo for adult and pediatric members with transfusion-dependent B-thalassemia who meet specified clinical, laboratory, and documentation criteria; applies to Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyBetibeglogene Autotemcel (Zynteglo)

Policy CodePolicy CP PHAR.545

Change TypeMaterial clinical and operational updates

Effective Date11.01.22

Next Review Date

Key ActionSubmit prior authorization with required clinical documentation including transplant specialist attestation, recent negative HIV test (within 6 months), and member weight.

SourceLink

POLICY UPDATE CHANGES

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/year.

Approval duration extended from 3 months to 6 months to allow member preparation and gene therapy manufacture; clarified one-time dose only for continued authorization.

Added requirement for transplant specialist involvement/attestation and documentation of negative HIV test within last 6 months and member body weight measurement.

Added HCPCS code J3393 and removed prior miscellaneous HCPCS codes (J3590, C93991).

one-timedose limit per lifetime

6 monthsapproval duration

≥5 x10^6minimum CD34+ cells/kg

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Coverage Criteria

Initial Approval Criteria

Covered when ALL of the following are met for initial treatment (one-time dose only):

Eligibility: Diagnosis of B-thalassemia with genetic confirmation; prescribed by or in consultation with a hematologist and transplant specialist; member has not previously received gene therapy or allogeneic HSCT; member does not have current malignancy; member does not have advanced liver disease; dose contains a minimum of ≥ 5 x 10^6 CD34+ cells/kg; approval duration 6 months (one-time infusion per lifetime).

Transfusion-dependence: Documentation of either: (a) receipt of ~2,100 mL/kg packed red blood cells (pRBC) per year for the previous two years (unit conversion guidance in Appendix D) OR (b) receipt of ≥ 8 transfusions of pRBC per year for the previous two years (unit conversion guidance in Appendix D).measurement over previous two years

Unit conversion: 1 RBC unit ≈ 200–350 mL; see Appendix D for conversion guidance.

Transplant specialist attestation: Attestation from transplant specialist that member understands risks and benefits of alternative therapeutic options (e.g., allogeneic HSCT) and that member is clinically stable and eligible to undergo myeloablative conditioning and HSCT.

Required as part of initial criteria.

Laboratory and administrative: Documentation from within the last 6 months of a negative HIV-1/2 test; documentation of member's body weight in kg; member does not have current malignancy; member does not have advanced liver disease.HIV test within 6 months

Body weight needed to verify dose calculations.

Continued Therapy

Continued Therapy: Continued therapy will not be authorized as Zynteglo is indicated to be dosed one time only.

Therapy is a one-time infusion per lifetime; continuation/renewal requests are not authorized.

High-level eligibility and authorization criteria

Covered when ALL of the following are met (high-level items reflected in these chunks):

age: Member is age >= 4 years>= 4 years

Lower age limit revised in 3Q 2024

transfusion_history: Transfusion history consistent with transfusion-dependent B-thalassemia (e.g., receipt of ≥ 8 transfusions/year or equivalent volume per year measured over the prior two years); age qualifier removed for this transfusion criterion.>= 8 transfusions/year

Age qualifier (≥ 12 years) removed

HIV_test: Negative HIV test documented within the last 6 monthswithin 6 months

Diagnoses/Indications that are not FDA‑approved for betibeglogene autotemcel (Zynteglo) are not authorized under this policy unless the provider submits sufficient documentation of efficacy and safety consistent with the referenced off‑label use policies (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other applicable evidence of coverage.

There are no explicit clinical exclusions listed in the portions of the policy provided. Operational and eligibility requirements (age, transfusion history, laboratory testing, prior therapies, and documentation requirements) are outlined elsewhere in the policy and govern authorization decisions.

Requests for use of Zynteglo for indications that are not FDA‑approved will be considered not authorized (not covered) unless the request includes adequate off‑label supporting documentation of efficacy and safety per the referenced off‑label use policies. Absent that documentation, such requests may be denied.

Not specified in the provided portions of the document.

Coding

Covered HCPCS CodesHCPCSCovered

J3393

Injection, betibeglogene autotemcel, per treatment

Covered HCPCS Codes (updated)HCPCSCovered

J3393

HCPCS code added for betibeglogene autotemcel

Removed HCPCS CodesHCPCSNot Covered

J3590	HCPCS code removed
C93991	HCPCS code removed

Minimum CD34+ cells/kg

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

Dose contextMinimum dose per FDA labeling for B‑thalassemia; no maximum dose specified

Documentation sourceDose requirement documented in policy dosing and administration and clinical criteria sections

Minimum age

Minimum age for therapy>= 4 years

Change noteLower age limit revised to ≥ 4 years (3Q 2024 annual review)

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zynteglo (HCPCS J3393). Providers must obtain prior authorization before administration. Approval duration: 6 months to allow for member preparation and gene therapy manufacture. This is a one-time dose only; continued authorization will not be granted for additional doses.

Prior authorization required for HCPCS code J3393
Approval duration: 6 months (one-time infusion per lifetime)

Documentation Required

Submit Supporting Clinical Documentation

Provider must submit supporting clinical documentation (such as office notes, lab results, or other relevant clinical information) demonstrating that the member meets all approval criteria. All requests will require medical director review.

Include office chart notes, relevant lab results, and any specialty consult notes (e.g., transplant specialist)

Definitions

Zynteglo

ProductBetibeglogene autotemcel (Zynteglo): autologous hematopoietic stem cell–based gene therapy

IndicationFor treatment of adult and pediatric patients with B‑thalassemia who require regular RBC transfusions

Dosing approachOne-time infusion following myeloablative conditioning; requires adequate CD34+ cell dose

pRBC unit conversion

Definition of 1 RBC unitApproximately 200–350 mL per RBC unit

Conversion for 350 mL bagsDivide transfused volume (mL) by 350 to convert to RBC units

Conversion for 200 mL bags

Background

Betibeglogene autotemcel (Zynteglo) is an autologous hematopoietic stem cell–based gene therapy indicated for adult and pediatric patients with transfusion‑dependent B‑thalassemia. The therapy is administered as a one‑time infusion following myeloablative conditioning and requires collection of an adequate CD34+ cell dose. The policy reflects recent updates including a revised minimum age threshold (now ≥ 4 years), documentation requirements such as a negative HIV test within the last 6 months and verification of member body weight, and operational changes to allow an authorization period of up to 6 months to permit member preparation and manufacture of the gene therapy.

Revision History

2024-08-24annual_review/material_changeLatest

3Q 2024 annual review: revised lower age limit to ≥4 years; removed age qualifier of ≥12 years for the ≥8 transfusions/year option; clarified negative HIV test must be within the last 6 months; extended approval duration from 3 months to 6 months to allow for member preparation and gene therapy manufacture; clarified therapy is authorized as a one-time dose for continued authorization.

2024-06-03coding_update

Added HCPCS code J3393 and removed HCPCS codes J3590 and C93991.

2022-11-22approval/criteria_update

Policy Summary

PayerCentene

PolicyBetibeglogene Autotemcel (Zynteglo)

Policy CodePolicy CP PHAR.545

Change TypeMaterial clinical and operational updates

Effective Date11.01.22

Next Review Date

Key ActionSubmit prior authorization with required clinical documentation including transplant specialist attestation, recent negative HIV test (within 6 months), and member weight.

SourceLink

On This Page

Required prior to therapy

authorization_duration: Authorization granted for up to 6 months to allow for member preparation and therapy manufacture6 months

Changed from 3 months to 6 months

dose_limit: One-time dose only for continued authorizationone-time

Clarified in 3Q 2024

ApplicabilityApplies to both adult and pediatric patients meeting other clinical criteria

Documentation Required

Required Recent Labs and Weight

Documentation must include a recent (within the last 6 months) negative HIV-1/2 test result and documentation of the member's body weight in kilograms for dose verification. Providers should ensure these items are present at time of submission.

Negative HIV-1/2 test within the last 6 months
Member body weight in kg documented

Denial Risk

Documentation-Related Denial Risks

Requests that lack required documentation (for example, missing the negative HIV test within the last 6 months, missing body weight, or failure to obtain required transplant specialist attestations) or requests for non–FDA‑approved indications without sufficient off‑label evidence per applicable off‑label policies may be denied.

Missing HIV-1/2 test within 6 months may result in denial
Missing body weight documentation may result in denial
Insufficient documentation for off‑label use may result in denial

Divide transfused volume (mL) by 200 to convert to RBC units

continued authorization

Continued authorization policyTherapy authorized as a one-time dose only (no continued/maintenance dosing)

Authorization lifetimeOne-time infusion per member lifetime

Operational clarificationContinued therapy will not be authorized as Zynteglo is indicated to be dosed one time only

HIV testing requirement

HIV testing requirementDocumentation of negative HIV-1/2 test within the last 6 months

Documentation timeframeHIV test must be from within 6 months prior to therapy

Associated requirementsNegative HIV test is required along with other pre-treatment documentation (e.g., body weight) for prior authorization

P&T Approval Date 11.22: minimum dose criteria updated per FDA labeling and transplant specialist involvement added; transfusion-dependence options clarified to be measured per year for the previous two years.

2021-07-13policy_creation

Policy created pre-emptively (pre-FDA approval) with initial creation date and subsequent P&T activity through 2021–2022 as documented.