Study Design and Population:

This open-label, single-group, phase 3 trial investigated the efficacy of exagamglogene autotemcel (exa-cel), a nonviral CRISPR-Cas9 gene-edited cell therapy, in patients aged 12 to 35 with transfusion-dependent β-thalassemia. Various genotypes were included, and participants underwent myeloablative conditioning followed by exa-cel infusion. The primary endpoint was to achieve and maintain transfusion independence.

Main Findings:

Of the 52 patients treated, 35 with sufficient follow-up showed that 32 (91%) achieved transfusion independence for at least 12 months, significantly surpassing the study’s efficacy threshold. The average total hemoglobin during this period was 13.1 g/dL, with fetal hemoglobin averaging 11.9 g/dL and widely distributed across red cells. The treatment’s safety profile was compatible with the expected outcomes of myeloablative conditioning and autologous hematopoietic stem cell transplantation, with no reported deaths or cancer developments.

Implications for Practice:

The successful achievement of transfusion independence in a high percentage of patients suggests that exa-cel is a promising treatment option for transfusion-dependent β-thalassemia. This study supports the potential for gene-edited cell therapies to significantly improve outcomes in genetic blood disorders. Continued monitoring and further research are recommended to fully understand the long-term implications and safety of such treatments.

Reference: 

Reference: Locatelli, F. et al. (2024). Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia. New England Journal of Medicine. doi: 10.1056/NEJMoa2309673.