CurrentBlue Cross Blue Shield - IowaPolicy 05.05.34

Casgevy (exagamglogene autotemcel)

Prior authorization policy for Casgevy (exagamglogene autotemcel) for treatment of sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) in patients 12 years and older, including required documentation, prescriber specialty, clinical eligibility and exclusion criteria, dosing, quantity limits, continuation policy, and billing codes.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyCasgevy (exagamglogene autotemcel)

Policy CodePolicy 05.05.34

Change TypeRevised; clarified; billing code added

Effective DateOct 11, 2025

Next Review Date

Key ActionSubmission of required documentation (molecular/genetic testing, relevant chart notes/medical records) and prescriber specialty verification is necessary to initiate prior authorization review.

POLICY UPDATE CHANGES

Added HCPCS J3392 effective 1/1/25 for Injection, exagamglogene autotemcel, per treatment.

Policy lists FDA-approved indications for SCD and TDT in patients 12 years and older and establishes specific clinical eligibility and exclusion criteria.

Continuation of therapy limited to one lifetime treatment; repeat dosing considered investigational.

2Covered Indications

1Lifetime treatment limit (per member)

>=12Minimum age (years)

>=100 mL/kg or >=10 units

TDT transfusion threshold (per year)

Coverage Summary

Coverage stance: covered_with_criteria. Scope: prior authorization policy for Casgevy (exagamglogene autotemcel) for treatment of sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT) in patients >= 12 years, including required documentation, prescriber specialty, clinical eligibility and exclusion criteria, dosing, quantity limits, continuation policy, and billing codes. FDA indications: Casgevy is indicated for treatment of SCD and TDT in patients >= 12 years. Authorization is for a single dose with a 3-month authorization period (initial authorization). Policy limits therapy to one lifetime treatment.

Initial Therapy — Sickle Cell Disease (single dose, 3 months)

Sickle Cell Disease - Initial Authorization (single dose, 3 months)

Authorization of 3 months for a single dose may be granted when ALL of the following criteria are met:

ALL of the following

Member is 12 years of age or older
ONE of
- Bs/Bs
- Bs/Bo
- Bs/+
- Additional genotypes may be considered on a case-by-case basis based on disease severity
Member has a documented history of at least 2 severe vaso-occlusive events (VOEs) per year during the previous two years (see Appendix A for examples)>= 2 severe VOEs per year during the previous two years
See Appendix A for examples (acute pain event requiring medical facility visit and administration of pain medications or RBC transfusion; acute chest syndrome; priapism >2 hours requiring medical visit; splenic or hepatic sequestration)
Member has either experienced hydroxyurea (HU) failure or has intolerance or inability to tolerate HU
ABSENCE of the following (all must be absent)
- A known 10/10 HLA matched related donor willing to participate in an allogeneic HSCT
- Persistent AST or ALT greater than 3 times the upper limit of normal> 3x ULN
- Advanced liver disease (any one of: direct bilirubin > 2.5x ULN; MRI evidence of cirrhosis)direct bilirubin > 2.5x ULN
- Baseline prothrombin time greater than 1.5 times the upper limit of normal> 1.5x ULN
- Liver biopsy demonstrating cirrhosis, any evidence of bridging fibrosis, or active hepatitis
Member has a negative serologic test for HIV infection
Member has not received a prior hematopoietic stem cell transplant (HSCT)
Member has not received Casgevy or any other gene therapy previously

Initial Therapy — Transfusion-Dependent Beta-Thalassemia (single dose, 3 months)

Transfusion-Dependent B-Thalassemia - Initial Authorization (single dose, 3 months)

Authorization of 3 months for a single dose may be granted when ALL of the following criteria are met:

ALL of the following

Member is 12 years of age or older
Member has a diagnosis of transfusion-dependent B-thalassemia with a non-BO/BO OR BO/BO genotype confirmed via molecular or genetic testing (see Appendix B)
See Appendix B for example genotypes
Member has received at least 100 mL/kg or 10 units of packed red blood cells (pRBCs) per year during the previous two years>= 100 mL/kg or >= 10 units pRBCs per year during the previous two years
ABSENCE of the following (all must be absent)

Continuation of Therapy and Repeat Treatment

Continuation of Therapy

Policy for repeat treatment

ALL of the following

Repeat treatment of Casgevy for any indication is considered investigational as safety and efficacy beyond one dose has not been studied
Approval is limited to one treatment course per lifetime

Not Medically Necessary

Casgevy is considered not medically necessary when the following apply:

ANY of the following

Member does not meet the criteria set forth above for the relevant indication

Exclusions / Not Covered

Exclusions and investigational conditions: Authorization requires the ABSENCE of active or uncontrolled bacterial, fungal, parasitic, or viral infections, including active/uncontrolled HBV and HCV; prior or current malignancy (except basal or squamous cell carcinoma of the skin); significant immunodeficiency disorders; contraindications to conditioning agents such as plerixafor and busulfan (including hypersensitivity to active substances or excipients); advanced liver disease defined by any of: persistent AST or ALT > 3x ULN, direct bilirubin > 2.5x ULN, MRI evidence of cirrhosis, baseline PT or PTT > 1.5x ULN, or liver biopsy showing cirrhosis/bridging fibrosis/active hepatitis; abnormal coagulation (PT/PTT > 1.5x ULN); white blood cell count < 3 x 10^9/L and/or platelet count < 50 x 10^9/L not related to hypersplenism; and, for TDT, myocardial iron T2* < 10 msec is an exclusion. Repeat dosing is considered investigational and approvals are limited to one lifetime treatment.

Applicable Codes

HCPCS / J-codes and unclassified codes for CasgevyHCPCSCovered

J3490	Unclassified drugs (when specified as [Casgevy] (exagamglogene autotemcel))
J3392	Injection, exagamglogene autotemcel, per treatment (effective 1/1/25)
J3590	Unclassified biologics (when specified as [Casgevy] (exagamglogene autotemcel))
C9399	Unclassified drugs or biologics (when specified as [Casgevy] (exagamglogene autotemcel))

Provider Actions & Documentation Requirements

Prior Authorization

Prior authorization required

Submission of required documentation (molecular/genetic testing results, relevant chart notes/medical records documenting VOEs for SCD or transfusion history for TDT) is necessary to initiate prior authorization review. Prescriber must be a hematologist or transplant specialist or in consultation with one. Required documentation submission initiates the prior authorization review and prescriber specialty requirements must be met.

Documentation Required

Required documentation for SCD

Provide molecular or genetic testing results documenting sickle cell disease genotype and chart notes or medical records documenting history of severe vaso-occlusive episodes (at least 2 VOEs per year for the previous two years).

Clinical Evidence

Key evidence and guidance: primary clinical evidence cited is Frangoul et al., N Engl J Med 2021 (CRISPR–Cas9 gene editing for SCD and B-thalassemia). Product labeling is cited as Casgevy package insert, Vertex Pharmaceuticals, January 2024. The policy intent is to align coverage with FDA labeling and evidence-based guidance.

Key Clinical Thresholds

Eligibility Thresholds

Age>= 12 years

VOE frequency (SCD)>= 2 severe VOEs per year during the previous two years

Transfusion volume (TDT)>= 100 mL/kg or >= 10 units pRBCs per year during the previous two years

White blood cells (WBC)>= 3 x 10^9/L (must not be < 3 x 10^9/L unless due to hypersplenism)

Platelets>= 50 x 10^9/L (must not be < 50 x 10^9/L unless due to hypersplenism)

Myocardial T2* (TDT)>= 10 msec (exclusion if < 10 msec)

Lifetime treatment limit1

Background

Background: Casgevy (exagamglogene autotemcel) is a gene-editing therapy indicated for the treatment of sickle cell disease (SCD) and transfusion-dependent B-thalassemia (TDT) in patients >= 12 years. The policy’s intent is to provide coverage consistent with FDA labeling and evidence-based guidance; approvals are contingent on meeting the clinical criteria specified in the policy and absence of listed exclusions.

Definitions: Severe vaso-occlusive events (VOEs) — examples include acute pain events requiring a visit to a medical facility and administration of pain medications or RBC transfusion, acute chest syndrome, priapism lasting > 2 hours requiring medical visit, splenic sequestration, and hepatic sequestration.

Revision History

2025-01-01billing_code_added

HCPCS J3392 (Injection, exagamglogene autotemcel, per treatment) listed with effective date 1/1/25.

2025-08-01policy_revision

Policy revised to include required documentation, prescriber specialty (hematologist or transplant specialist), specific dosing guidance, and explicit clinical eligibility and exclusion criteria for FDA-approved indications (SCD and TDT in patients >=12 years). Prior authorization requirements and documentation specifics for SCD and TDT were detailed.

2025-08-01policy_clarification

Clarified continuation policy: approval is limited to one treatment course per lifetime; repeat dosing is considered investigational and not covered.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyCasgevy (exagamglogene autotemcel)

Policy CodePolicy 05.05.34

Change TypeRevised; clarified; billing code added

Effective DateOct 11, 2025

Next Review Date

On This Page

Active bacterial, fungal, parasitic, or viral infection, including active/uncontrolled HBV and HCV infection

Prior or current malignancy (except basal or squamous cell carcinoma of the skin) or significant immunodeficiency disorder

Contraindication to the use of plerixafor; busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to active substances or excipients

White blood cell count < 3 x 10^9/L and/or platelet count < 50 x 10^9/L not related to hypersplenismWBC >= 3 x 10^9/L; Platelets >= 50 x 10^9/L

Exclusion applies if counts are below thresholds unless due to hypersplenism

Associated alpha-thalassemia with greater than alpha deletion or alpha multiplications
Sickle cell beta thalassemia variant
T2*-weighted MRI measurement of myocardial iron < 10 msec or other evidence of severe iron overload in the opinion of treating physicianMyocardial T2* >= 10 msec required (exclude if < 10 msec)
Availability of HLA-identical or HLA-matched donor willing to participate in allogeneic HSCT
Advanced liver disease (any one of: persistent AST or ALT > 3x ULN; MRI evidence of cirrhosis; baseline PT or PTT > 1.5x ULN; liver biopsy demonstrating cirrhosis, bridging fibrosis, or active hepatitis)AST/ALT > 3x ULN; PT/PTT > 1.5x ULN
Active bacterial, fungal, parasitic, or viral infection, including active/uncontrolled HBV and HCV infection
Prior or current malignancy (except basal or squamous cell carcinoma of the skin) or significant immunodeficiency disorder
Contraindication to the use of busulfan, or any other medicinal products required during myeloablative conditioning, including hypersensitivity to the active substances or excipients
White blood cell count < 3 x 10^9/L and/or platelet count < 50 x 10^9/L not related to hypersplenismWBC >= 3 x 10^9/L; Platelets >= 50 x 10^9/L
Exclusion applies if counts are below thresholds unless due to hypersplenism

Member has a negative serologic test for HIV infection

Member has not received Casgevy or any other gene therapy previously

Member has not received a prior hematopoietic stem cell transplant (HSCT)

Documentation Required

Required documentation for TDT

Provide molecular or genetic testing results documenting transfusion-dependent B-thalassemia genotype and chart notes or medical records documenting history of blood transfusions (at least 100 mL/kg or 10 units of packed red blood cells per year during the previous two years).

Documentation Required

Laboratory and clinical exclusions

Document baseline laboratory and clinical evaluations to confirm absence of exclusions prior to therapy: baseline AST/ALT, bilirubin, coagulation parameters (prothrombin time/partial thromboplastin time), liver imaging and/or biopsy results, HIV serology, white blood cell and platelet counts, and documentation of absence of active bacterial, fungal, parasitic, or viral infections and any contraindications to conditioning agents (e.g., plerixafor, busulfan).

AST and ALT
Total and direct bilirubin
Prothrombin time (PT) and partial thromboplastin time (PTT)
Liver imaging (MRI) and/or liver biopsy
HIV serologic test
White blood cell count and platelet count
Documentation of absence of active infections (including uncontrolled HBV/HCV)
Documentation of no contraindication to conditioning agents (plerixafor, busulfan, etc.)

Billing Rule

Limit to one treatment per lifetime

Casgevy approvals will be limited to one treatment course per lifetime; repeat treatment for any indication is considered investigational.

Affected billing codes: J3392; J3490; J3590; C9399
Repeat dosing considered investigational

2025-10-11policy_effective_dateLatest

Current policy effective; aligns coverage with FDA labeling and evidence-based guidance for Casgevy with the specified clinical criteria, documentation, dosing recommendation (3 x 10^6 CD34+ cells/kg), quantity limits (one lifetime treatment), and billing codes including J3392.