OBJECTIVES: Exagamglogene autotemcel (exa-cel) is an autologous gene edited therapy with the potential to provide a functional cure for patients with transfusion-dependent beta-thalassemia (TDT). In Canada, standard of care (SOC) for TDT includes regular red blood cell transfusions (RBCTs) and iron chelation therapy. A model was developed to project survival and long-term clinical outcomes of exa-cel versus SOC in Canada for patients with TDT.

METHODS: A Markov model driven by transfusion status was developed to project survival and clinical outcomes over a lifetime. The modeled population was 21.1 years old with 17.2 RBCTs/year; approximately 91% of patients treated with exa-cel were assumed to achieve transfusion independence (TI); the remaining 9% experienced reductions in RBCTs, based on the pre-specified interim analysis of the CLIMB THAL-111 Phase 3 trial in patients ages 12 years and older published in Locatelli et al. 2024 N Engl J Med (data as of January 2023). Patients who reached TI were assumed to have no additional complications beyond those present at baseline. Patients receiving SOC were assumed to remain transfusion dependent throughout their lifetime. Complication risks and mortality inputs were derived from published literature. Modeled outcomes included projected survival, RBCT frequency, and proportion of patients developing complications.

RESULTS: In Canada, exa-cel was projected to increase survival by 18.7 years compared to SOC (mean age at death: 68.0 vs 49.3). Compared to SOC, patients treated with exa-cel received 459.8 fewer RBCTs over a lifetime (24.7 vs 484.5). Additionally, exa-cel lowered the proportion of patients with complications over a lifetime compared to SOC, including hypogonadism (12.76% vs 67.52%), diabetes (10.06% vs 47.36%), osteoporosis (13.69% vs 44.31%), and cardiac complications (6.57% vs 27.72%).

CONCLUSIONS: Model projections suggest exa-cel could substantially improve survival, lower the prevalence of TDT-related complications, and reduce disease burden in patients with TDT in Canada compared to treatment with SOC.