OBJECTIVES: Exagamglogene autotemcel (exa-cel) is a one-time potentially curative gene-edited therapy being evaluated for patients with transfusion-dependent β-thalassemia (TDT). The standard of care (SOC) for TDT includes regular red blood cell transfusions (RBCTs) and iron chelation therapies from early childhood. A model was developed to assess the potential long-term clinical outcomes of exa-cel versus SOC in the United Kingdom for patients with TDT.

METHODS: A Markov cohort model was developed to compare clinical outcomes of exa-cel versus SOC over a lifetime horizon. The modeled population had a baseline age of 21.8 years with 17.2 RBCTs/year based on published trial data. Clinical efficacy of exa-cel was informed from published trial data; time to iron normalization was varied from 2 to 5 years. Patients receiving SOC were assumed to continue RBCTs at the baseline rate and maintain baseline iron levels. Mortality was estimated based on transfusion status and presence of TDT-related complications. Complication risks and mortality inputs were derived from published literature. Modeled outcomes included survival, number of RBCTs over a lifetime, and proportion of patients developing complications.

RESULTS: The model projected that patients treated with exa-cel had substantial increases in survival ranging from 17.8-20.5 years compared to SOC, depending on time to iron normalization (mean predicted age at death: exa-cel: 68.2-70.8 vs. SOC: 50.3). Patients treated with exa-cel received 465-466 fewer RBCTs over a lifetime compared to SOC (exa-cel: 25-26 vs SOC: 491). Over a lifetime, exa-cel substantially lowered the proportion of patients developing complications compared to SOC, including hypogonadism (exa-cel: 9.7-12.0% vs SOC: 69.1%), diabetes (exa-cel: 4.4-5.0% vs SOC: 45.9%), and osteoporosis (exa-cel: 4.9-5.3% vs SOC: 39.8%).

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