Five-year durability in cell and gene therapy: evidence review and implications for payer coverage

INTRODUCTION: Cell and gene therapies (CGTs) offer the potential for durable clinical benefit following a single administration. Although early regulatory approvals were often based on limited follow-up, an increasing number of U.S. Food and Drug Administration (FDA)-approved CGTs now report extended durability data from clinical trials and real-world evidence (RWE) studies. AREAS COVERED: This report synthesizes publicly available long-term follow-up (LTFU) evidence for FDA-approved CGTs in the United States, with a focus on durability of clinical benefit and the implications for payer coverage and reimbursement. Long-term efficacy and safety data for marketed CGTs were identified through a review of peer-reviewed publications and publicly available conference abstracts and presentations. As of December 2025, 21 therapies (62%) report follow-up extending to 5 years or longer. The review examines the available durability evidence and explores its relevance to ongoing discussions around durability-related uncertainty and the role of LTFU and real-world evidence in assessing CGT outcomes. EXPERT OPINION: Growing LTFU evidence suggests that durable clinical benefit can be achieved across multiple CGT platforms and disease settings. While uncertainties remain, accumulating data may help reduce durability-related uncertainty and inform payer coverage, reimbursement, and value assessment discussions.