Exagamglogene autotemcel (Casgevy™)

Restricted Product(s)

• exagamglogene autotemcel (Casgevy™) intravenous infusion for administration by a healthcare professional

FDA Approved Use

• For treatment of patients aged 12 years and older with:
  • Sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) 
  • Transfusion-dependent β-thalassemia (TDT)

Criteria for Medical Necessity

The restricted product(s) may be considered medically necessary when the following criteria are met:

1. The patient is 12 years of age or older; AND 
2. ONE of the following: 
   1. The patient has a diagnosis of sickle cell disease (SCD) [medical record documentation required]; AND 
      1. The patient’s diagnosis has been confirmed by genetic testing demonstrating a βS /βS or βS /β0 or βS /β+ genotype [medical record documentation required]; AND 
      2. The patient has experienced at least four severe vaso-occlusive crisis (VOC) events*** in the past 24 months in the setting of appropriate supportive care measures for SCD (e.g., pain management plan) [medical record documentation required]; AND 
      3. ONE of the following: 
         1. The patient has tried and had an inadequate response to hydroxyurea [medical record documentation required]; OR 
         2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to hydroxyurea [medical record documentation required]; OR 
   2. The has a diagnosis of transfusion-dependent β-thalassemia (TDT) [medical record documentation required]; AND 
      1. The patient’s diagnosis has been confirmed by genetic testing demonstrating either homozygous β-thalassemia or compound heterozygous β-thalassemia, including β-thalassemia/hemoglobin E (HbE) [medical record documentation required]; AND 
      2. The patient has required regular red blood cell (RBC) transfusions defined as the following [medical record documentation required]:
         1. A history of at least 100 mL/kg/year of packed RBC transfusions during the past 2 years [medical record documentation required]; OR 
         2. A history of at least 10 units/year of packed RBC transfusions in the past 2 years [medical record documentation required]; AND
3. The patient is clinically fit to undergo autologous stem cell transplantation [e.g., Karnofsky performance status of ≥ 60 (16 years of age or older) or Lansky performance status of ≥ 60 (less than 16 years of age)] [medical record documentation required]; AND 
4. The patient is a candidate for an allogeneic hematopoietic cell transplantation but has NO available willing and healthy 10/10 human leukocyte antigen (HLA)-matched related hematopoietic-cell donor [medical record documentation required]; AND 
5. The patient has adequate bone marrow function, as defined by a white blood cell count of 3,000/µL or greater or a platelet count of 50,000/µL or greater [medical record documentation required, including lab tests within the past 3 months]; AND 
6. The patient does NOT have associated α-thalassemia nor presence of greater than one alpha chain deletion [medical record documentation required]; AND 
7. The patient is able to receive red blood cell (RBC) transfusions [medical record documentation required]; AND 
8. The patient does NOT have severe cerebral vasculopathy, including ONE or more of the following [medical record documentation required]: 
   1. Any history of overt ischemic or hemorrhagic stroke; OR 
   2. More than 50% stenosis or occlusion in the circle of Willis; OR 
   3. Presence of Moyamoya disease; AND 
9. The patient does NOT have advanced liver disease, including ONE or more of the following [medical record documentation required]: 
   1. Clear evidence of liver cirrhosis, active hepatitis, or significant fibrosis; OR 
   2. Liver iron concentration of 15 mg/g or greater unless liver biopsy shows no evidence of cirrhosis, active hepatitis, or significant fibrosis; AND 
10. The patient does NOT have any evidence of chronic kidney disease [medical record documentation required]; AND 
11. The patient does NOT have a history of iron overload demonstrated by cardiac T2* < 10 ms [medical record documentation required]; AND 
12. The patient does NOT have clinically significant pulmonary hypertension prior to starting treatment with the requested agent [medical record documentation required]; AND 
13. The patient is NOT human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2) positive [medical record documentation required, including lab tests within the past 3 months]; AND 
14. The patient’s hepatitis B surface antigen is negative [medical record documentation required, including lab results within the past 3 months]; AND 
15. ONE of the following:
    1. The patient’s hepatitis C virus (HCV) antibody is negative [medical record documentation required, including lab results within the past 3 months]; OR 
    2. The patient’s HCV antibody is positive AND the patient’s HCV RNA is negative [medical record documentation required, including lab results within the past 3 months]; AND
16. The patient does NOT have any prior or current malignancy or immunodeficiency disorder, with the exception or non-melanoma skin cancers, nor have any immediate family members with a known or suspected Familial Cancer Syndrome [medical record documentation required]; AND 
17. The patient does NOT have any clinically significant and active bacterial, viral, fungal, or parasitic infection [medical record documentation required]; AND 
18. The patient does NOT have any contraindications to use of plerixafor during the mobilization of hematopoietic stem cells nor any contraindications to use of busulfan and any other medications required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients [medical record documentation required]; AND 
19. The patient has NOT received prior allogeneic hematopoietic stem cell transplantation [medical record documentation required]; AND 
20. The patient has NOT received any previous gene therapy, including the requested agent [medical record documentation required]; AND 
21. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist, SCD or TDT specialist, transplant specialist) or has consulted with a specialist in the area of the patient’s diagnosis [medical record documentation required]; AND 
22. The requested dose is within FDA labeled dosing for the requested indication, and the requested quantity does NOT exceed the maximum units allowed for the duration of approval (see table below) [medical record documentation required].
    
    Duration of Approval: 365 days (1 year); one-time, single-dose treatment per lifetime

**Please note, for certain identified gene and cellular therapies such as exagamglogene autotemcel (Casgevy™), when coverage is available and the individual meets medically necessary criteria, distribution from a specialty pharmacy provider due to cost (distribution channel restriction) may be required in order for coverage to be provided. Please contact BCBS NC to coordinate this therapy.

***A severe VOC event is defined as an acute episode of pain with no medically determined cause other than a vaso-occlusion, requiring a medical facility visit and treatment with pain medications (i.e., oral or parenteral opioids, or parenteral NSAIDs) or red blood cell (RBC) transfusions. Severe VOC events may include acute chest syndrome, acute hepatic sequestration, acute splenic sequestration, and/or acute priapism lasting more than 2 hours and requiring care at a medical facility.

References

All information referenced is from FDA package insert unless otherwise noted below.

1. Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia. N Engl J Med. 2021;384(3):252-260.

Policy Implementation/Update Information

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

February 2024: Original medical policy criteria issued.