OBJECTIVES: Exagamglogene autotemcel (exa-cel) is an autologous gene edited therapy with the potential to provide a functional cure for patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs). In Canada, standard of care (SOC) for SCD includes hydroxyurea and red blood cell transfusions. A model was developed to project survival and long-term clinical outcomes of exa-cel versus SOC in Canada for patients with SCD with recurrent VOCs.

METHODS: A Markov cohort model driven by disease response-based health states, which determined occurrence of VOCs and SCD-related complications, projected survival and clinical outcomes over a lifetime. Modeled population baseline characteristics and efficacy assumptions were based on an interim analysis of the CLIMB SCD-121 Phase 3 trial in patients 12 years and older published in Frangoul et al. 2024 N Engl J Med (data as of June 2023). Approximately 97% of patients treated with exa-cel were assumed to achieve a curative health state. Patients in the curative health state were assumed to experience no additional VOCs or SCD-related complications beyond those present at baseline. Patients receiving SOC were assumed to maintain the baseline VOC rate. Complication risks and mortality inputs were derived from published literature. Modeled outcomes included projected survival and long-term clinical outcomes.

RESULTS: In Canada, exa-cel was projected to increase survival by 24.6 years compared to SOC (mean age of death: 74.3 vs 49.7). Patients receiving exa-cel experienced 100.4 fewer VOCs (7.4 vs 107.8) and fewer acute complication events over a lifetime. Exa-cel lowered the proportion of patients with chronic complications compared to SOC, including avascular necrosis (34.2% vs 77.5%) and retinopathy (8.7% vs 32.7%).

CONCLUSIONS: Model projections suggest exa-cel could substantially improve survival and lower the incidence of VOCs and complications over a lifetime in patients with SCD with recurrent VOCs in Canada compared to treatment with SOC.