OBJECTIVES: Exagamglogene autotemcel (exa-cel) is a one-time potentially curative gene-edited therapy being evaluated for patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs). The standard of care (SOC) for these patients includes hydroxyurea and red blood cell transfusions. In this study, we assessed the potential cost-effectiveness of exa-cel versus SOC in the United States (US) for patients with SCD with recurrent VOCs.

METHODS: A Markov cohort model was developed to compare clinical and cost outcomes of exa-cel versus SOC over a lifetime horizon from a US payer perspective. The base-case modeled population had a mean age of 22.5 years with 3.9 VOCs/year. Modeled outcomes included proportion of patients developing chronic complications, number of VOCs and acute complication events, life years (LYs), quality-adjusted life years (QALYs), costs, and cost-effectiveness using a $150,000/QALY willingness-to-pay (WTP) threshold. Clinical efficacy was informed from published exa-cel clinical trial data; SOC inputs were derived from published literature. Complication risks, utility, mortality, and cost inputs were also derived from published literature. Costs and outcomes were discounted 3% annually. Mean age and number of VOCs were varied to provide a range of outcomes.

RESULTS: Compared to SOC, exa-cel is projected to improve patient survival (undiscounted) by 20.1–22.5 years and lower the number of VOC events by 56–175 over a lifetime. Exa-cel results in improved discounted LYs (+7.2–9.1) and discounted QALYs (+11.0–12.9), as well as reduced undiscounted disease management costs ($2,340,000–$3,790,000) versus SOC. At a $150,000/QALY WTP threshold, exa-cel would be cost-effective at prices ranging from $2,880,000 to $4,510,000.

CONCLUSIONS: Model projections suggest that exa-cel could considerably improve survival and quality-of-life and reduce disease management costs and the incidence of VOCs and complications in patients with SCD with recurrent VOCs compared to SOC.