CurrentCignaPolicy N/A

Cigna Gene Therapy Prior Authorization for Zynteglo

Form and criteria governing prior authorization requests for the gene therapy product Zynteglo for patients with beta-thalassemia; applies to providers submitting requests to Cigna's Gene Therapy Program.

Policy Summary

PayerCigna

PolicyCigna Gene Therapy Prior Authorization for Zynteglo

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionComplete and fax the Gene Therapy Prior Authorization form with required supporting clinical documentation to 833-910-1625.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

ZyntegloProduct

≥4 yrsMin age

≥100 mL/kg or ≥8/yrTransfusion-def

≥11.0 g/dLHemoglobin

Coverage Criteria for Zynteglo

Initial Therapy — Zynteglo

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Zynteglo is considered medically necessary when ALL of the following groups and nested conditions are met.

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)
- Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)
Iron overload assessment: Patient has been evaluated for severe iron overload (documentation required) AND does not have evidence of severe iron overload (examples: myocardial T2* < 10 msec; liver iron concentration ≥ 15 mg/g; liver biopsy abnormalities; or clinical evidence of organ damage)
Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection
Malignancy/immunodeficiency exclusion: No prior or current malignancy, myeloproliferative disorder, or significant immunodeficiency disorder (note: adequately treated cone‑biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin are not considered exclusions)
Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning
Mobilization and conditioning plan: Per prescriber: patient will undergo mobilization, apheresis, and myeloablative conditioning; a G-CSF product and a hematopoietic stem cell mobilizer (e.g., plerixafor) will be used for mobilization; busulfan will be used for myeloablative conditioning; total hemoglobin ≥ 11.0 g/dL at BOTH timepoints: (a) prior to mobilization and (b) prior to myeloablative conditioning
Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2
Reproductive risk mitigation
- Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
- Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration
Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

Overall requirements

Basic eligibility: Patient is ≥ 4 years of age; patient has not received prior gene therapy for beta-thalassemia; hematopoietic stem cell transplantation is appropriate per the prescribing physician
Genotype
- Non-β0/β0 genotype with documentation (examples: β0/β+, βE/β0, β+/β+)
- β0/β0 genotype with documentation (examples include β0/β+(IVS-I-110) and β+(IVS-I-110)/β+(IVS-I-110))
Transfusion dependence
- Volume-based: Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years (documentation required)

The policy clarifies that certain localized, adequately treated skin and cervix lesions are not considered exclusions for Zynteglo. Specifically, adequately treated cone‑biopsied carcinoma in situ of the cervix uteri and basal or squamous cell carcinoma of the skin are explicitly not included among the malignancy exclusions noted on the form. Providers should document treatment history for these conditions as part of the submission when relevant.

Patients with certain active or historical conditions do not meet medical necessity for Zynteglo unless appropriate documentation and justification are provided. The form requires that the patient have no prior or current malignancy, myeloproliferative disorder, or significant immunodeficiency disorder, and that they do not currently have an active bacterial, viral, fungal, or parasitic infection. Additionally, the policy requires negative infectious disease screening (including HIV‑1/2 and hepatitis B and C) and documentation that the patient has been evaluated for and does not have evidence of severe iron overload.

Coding and Clinical Thresholds

Cell collection CPT codesCPT

96372	Therapeutic, prophylactic, or diagnostic injection; subcutaneous or intramuscular
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous

Mobilization agents (J/Q codes)HCPCS

J2562	Injection, plerixafor, 1 mg (Mozobil)
J1442	Injection, filgrastim, excludes biosimilar, 1 mcg
J1447	Injection, tbo-filgrastim, 1 mcg
Q5101	Injection, filgrastim-sndz, biosimilar, (Zarxio), 1 mcg
Q5110	Injection, filgrastim-aafi, biosimilar, (Nivestym), 1 mcg
Q5125	Injection, filgrastim-ayow, biosimilar, (Releuko), 1 mcg

Conditioning agentHCPCS

J0594

Injection, busulfan, 1 mg

inv-07: Hemoglobin threshold

Hemoglobin thresholdTotal hemoglobin ≥ 11.0 g/dL at both timepoints: (a) prior to mobilization and (b) prior to myeloablative conditioning

Applicable timepointsPrior to mobilization; Prior to myeloablative conditioning

Measurement unitsgrams per deciliter (g/dL)

inv-08: Transfusion dependence definition

Transfusion-dependence (volume-based)Receipt of ≥100 mL packed red cells per kg of body weight per year in the previous 2 years

Transfusion-dependence (frequency-based)Receipt of transfusions eight or more times per year in the previous 2 years

Documentation timeframePrior 2 years (documentation required)

Provider Actions and Submission Requirements

Prior Authorization

Prior authorization required — fax completed form to 833-910-1625

Complete and fax the Gene Therapy Prior Authorization form with all required supporting clinical documentation to the Gene Therapy Program at Fax# 833-910-1625 to initiate coverage review for Zynteglo.

Step Therapy

Pre-infusion regimen documentation — select agents and provide dosing/directions

Document the planned mobilization and conditioning regimen on the form by selecting the applicable mobilization agent(s) (plerixafor, filgrastim or listed biosimilars) and the conditioning agent busulfan, including prescriber directions, dosing, quantity, and duration.

Select the appropriate G‑CSF or plerixafor line item and provide 'Directions for use', Dose, Quantity, and Duration of therapy.
Select the busulfan line item under Conditioning Regimen and provide 'Directions for use', Dose, Quantity, and Duration of therapy.

Documentation Required

Supporting documentation required — attach chart notes, tests, and records

Include all supporting clinical documentation as indicated on the form — examples include chart notes, genetic test results, laboratory and medical test results, claims records, and prescription receipts.

Attach chart notes documenting eligibility criteria (age, genotype, transfusion history, iron overload assessment).
Attach laboratory and diagnostic test results (e.g., genetic test reports, MRI/iron studies) and relevant claims or prescription records.

Documentation Required

Attestation and outcome‑sharing — prescriber signature and patient consent requested

Prescriber attestation and signature are required on the Agreement and Attestation section; the form also asks whether the patient agrees to share required plan‑specific outcome measures.

Complete the Attestation statement and provide Prescriber Signature and Date.
Indicate patient agreement to share outcome measures (Yes/No) as requested on the form.

Denial Risk

Incomplete submission risk — missing fields or documents may delay or result in denial

Failure to complete the form in its entirety or to include required supporting clinical documentation may delay processing or result in an adverse determination for insufficient information.

Ensure all asterisked fields are completed (fax responses cannot be returned unless these fields are filled).
Omit no required documentation — incomplete submissions risk delayed processing or denial.

Background

Zynteglo is a gene therapy indicated for patients with beta‑thalassemia who meet specific eligibility criteria. The prior authorization form captures key clinical requirements including patient age (≥4 years), genotype documentation (non‑β0/β0 or β0/β0 examples), and transfusion‑dependence as defined by either receipt of ≥100 mL packed red cells/kg/year or ≥8 transfusions per year over the prior two years. The form also requires assessment for iron overload and absence of severe iron burden (examples: myocardial T2* < 10 msec or liver iron concentration ≥ 15 mg/g), infection screening, reproductive risk mitigation, and confirmation of planned mobilization/apheresis and myeloablative conditioning with specified hemoglobin thresholds prior to mobilization and conditioning.

Key Definitions

inv-15: Transfusion-dependent definition

Volume criterionReceipt of ≥100 mL packed red cells per kg per year in the prior 2 years

Frequency criterionReceipt of ≥8 transfusions per year in the prior 2 years

Documentation requirementDocumentation of transfusion history for the previous 2 years is required

inv-16: Severe iron overload examples

Myocardial iron (T2*)Myocardial T2*-weighted MRI measurement of myocardial iron < 10 msec

Liver iron concentrationLiver iron concentration ≥ 15 mg/g

Liver biopsyLiver biopsy results suggesting abnormalities

Clinical organ damageClinical evidence of organ damage (e.g., endocrine comorbidities)

Policy Summary

PayerCigna

PolicyCigna Gene Therapy Prior Authorization for Zynteglo

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionComplete and fax the Gene Therapy Prior Authorization form with required supporting clinical documentation to 833-910-1625.

SourceLink

On This Page

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Iron overload assessment: Patient has been evaluated for severe iron overload (documentation required) AND does not have evidence of severe iron overload (examples: myocardial T2* < 10 msec; liver iron concentration ≥ 15 mg/g; liver biopsy abnormalities; or clinical evidence of organ damage)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Malignancy/immunodeficiency exclusion: No prior or current malignancy, myeloproliferative disorder, or significant immunodeficiency disorder (note: adequately treated cone‑biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin are not considered exclusions)

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Mobilization and conditioning plan: Per prescriber: patient will undergo mobilization, apheresis, and myeloablative conditioning; a G-CSF product and a hematopoietic stem cell mobilizer (e.g., plerixafor) will be used for mobilization; busulfan will be used for myeloablative conditioning; total hemoglobin ≥ 11.0 g/dL at BOTH timepoints: (a) prior to mobilization and (b) prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)

Frequency-based: Receipt of eight or more transfusions per year in the previous 2 years (documentation required)

Infection screening: Patient does not currently have an active bacterial, viral, fungal, or parasitic infection

Liver disease and chelation: Advanced liver disease must be documented when present; patient will be discontinued from iron chelation therapy at least 7 days prior to myeloablative conditioning

Infectious disease screening specifics: Negative screening documented for HIV‑1/2, hepatitis B, hepatitis C, and HTLV‑1/2

Reproductive risk mitigation

Female reproductive potential: Female: negative serum pregnancy test confirmed prior to mobilization and re‑confirmed prior to conditioning; use effective contraception from start of mobilization through at least 6 months after administration
Male reproductive potential: Male: use effective contraception from start of mobilization through at least 6 months after administration

Prescriber and documentation: Medication is prescribed by a hematologist or a stem cell transplant specialist and current patient body weight has been obtained within 30 days (documentation required)