(47) Payer policies and access restrictions for CRISPR-based gene therapy in sickle cell disease and beta-thalassemia: A systematic review of U.S. coverage frameworks

Background: : Exagamglogene autotemcel (Casgevy), a one-time CRISPR/Cas9 gene therapy, received FDA approval in December 2023 for sickle cell disease (SCD) and in January 2024 for transfusion-dependent beta-thalassemia (TDT). Although the therapy shows clinical promise, access has been constrained by high costs, limited treatment sites, and uncertain reimbursement. As availability expands, payer policies increasingly influence patient access.

Objective: : To examine how U.S. payers, including Medicaid programs, Medicare contractors, and commercial insurers, define coverage for Casgevy in SCD and TDT. Areas of focus included eligibility requirements, prior authorization, dosing restrictions, site-of-care policies, and reimbursement models.

Methods: : A systematic review was conducted from January 2023 through May 2025 following PRISMA 2020 guidelines. Sources included PubMed, Embase, CMS.gov, Medicaid websites, Medicare Administrative Contractor (MAC) portals, and commercial payer documents. Of 119 records identified, 89 full texts were screened and 28 were included. These comprised peer-reviewed articles, 13 Medicaid bulletins, 4 Medicare MAC coverage determinations from Palmetto GBA and Novitas, and 11 commercial policies. Two reviewers independently screened and extracted data using a structured tool. Discrepancies were resolved by consensus. Findings were grouped by payer type and coverage characteristics.

Results: : All 28 policies required patients to be at least 12 years old with documented severe disease. For SCD, most criteria included two or more vaso-occlusive crises annually, prior hospitalization, and failure or contraindication to hydroxyurea. For TDT, transfusion requirements ranged from 8 to 12 units per year. Twenty-six policies (93%) allowed a single lifetime dose. Twenty policies (71%) required administration at certified gene therapy or transplant centers. All prior authorization protocols required genetic confirmation and review by a specialist. Ten of 13 Medicaid programs referenced the Cell and Gene Therapy Access Model launched in January 2025. Five commercial payers reported piloting outcomes-based or milestone-based contracts. As of early 2025, an estimated 40 to 50 patients had started treatment, reflecting limited uptake and operational barriers.

Conclusions: : Coverage for Casgevy remains highly restrictive. Narrow criteria, constrained capacity, and uneven payment model adoption continue to limit access. Broader implementation will require coordination between payers and providers, expanded site readiness, and more consistent reimbursement approaches.

Sponsorship:: None