Cost-effectiveness of exagamglogene autotemcel gene-edited therapy in patients with transfusion-dependent <b><i>β</i></b>-thalassemia in the United States

Exagamglogene autotemcel (exa-cel) is a one-time nonviral gene-edited therapy approved in the United States (US) for treatment of patients aged ≥12 with transfusion-dependent β-thalassemia (TDT). Standard of care (SOC) for TDT includes regular red blood cell transfusions (RBCTs) and iron chelation therapy. This study estimated long-term clinical outcomes and cost-effectiveness of exa-cel vs. SOC among patients with TDT in the US. A Markov model was developed to compare the expected lifetime costs and clinical outcomes of patients with TDT treated with exa-cel compared to SOC from the US payer and societal perspectives. The model structure is based on transfusion status, which impacts iron levels and risk of developing TDT-related complications. The model incorporated data from the phase 3 pivotal CLIMB THAL-111 trial and other inputs from literature. Model outcomes included life years (LYs) and quality-adjusted LYs (QALYs) as well as number of RBCTs and proportion of patients developing complications over a lifetime; costs and incremental cost-effectiveness ratios (ICERs) were also estimated. Costs and outcomes were discounted at 3% annually. In the eligible patient population (average age at baseline: 21 years), exa-cel was projected to improve survival by 17.6 years (mean age of death, exa-cel: 64.9 years vs. SOC: 47.3 years), reduce the number of RBCTs received by 425 (exa-cel: 26 vs. SOC: 451), and lower the proportion of patients developing TDT-related complications. Exa-cel was associated with increased discounted costs compared to SOC (exa-cel: $2.9 M vs. SOC: $1.8 M). The ICER per discounted QALY for exa-cel versus SOC was $114,100 from the payer perspective and $55,400 from the societal perspective. Compared to SOC, exa-cel was projected to considerably reduce the number of RBCTs and TDT-related complications, improve survival, and reduce disease-related costs. Exa-cel is projected to be a cost-effective treatment option for patients with TDT in the US. Transfusion-dependent beta-thalassemia (TDT) is an inherited blood disorder which requires frequent red blood cell transfusions and medicines to remove extra iron in the body. These treatments help patients live longer but come with serious side effects and high costs over time. Exagamglogene autotemcel (exa-cel) is a one-time gene-editing therapy approved in the United States (US) for patients aged 12 years and older with TDT. Patients treated with exa-cel can become transfusion independent and live without the need for transfusions. This study used an economic model to compare exa-cel with standard treatment (frequent transfusions and iron removal therapy) in the US. The model estimated survival, occurrence of complications, quality of life, and costs from the time of exa-cel treatment (average age: 21 years) until death. The model predicted that patients treated with exa-cel would live about 18 years longer than those receiving standard treatment (average life expectancy 65 vs. 47 years) and also have better quality of life. Patients treated with exa-cel were also expected to need far fewer transfusions (26 vs. 451), experience fewer disease-related complications, and cost $2.2 million less in disease-related costs over a lifetime. In summary, exa-cel has the potential to greatly improve survival and quality of life for people with TDT, while reducing long-term health care costs, making it a valuable new treatment option.