Safety and efficacy of hemobeglogene autotemcel(hemo-cel) gene therapy in five patients with transfusion-dependent β-thalassemia.

Lentiviral vector-mediated hematopoietic stem cell gene therapy (HSC-GT) has emerged as a curative alternative to allogeneic transplantation for patients with transfusion-dependent β-thalassemia (TDT). However, challenges such as delayed platelet engraftment, variable transgene expression, and limited long-term safety data have hindered its broader implementation. Here, we report the safety and efficacy outcomes from a phase 1/2 clinical study evaluating hemobeglogene autotemcel (hemo-cel), an HSC-GT product developed with an optimized lentiviral vector encoding HBBT87Q and an improved manufacturing process. Five pediatric TDT patients, including three with β0/β0 genotypes, received hemo-cel and were followed for a median of 34.7 months. Hemo-cel infusion led to rapid neutrophil (median, day 18) and platelet (median, day 13) engraftment. No unexpected adverse events, clonal dominance, or replication-competent lentivirus were observed. All patients achieved transfusion independence for over 26 months (median, 34.3 months), with sustained HbAT87Q levels and vector copy numbers. Hemo-cel also contributed to iron overload control and supported normal growth in height and weight. These findings suggest that hemo-cel is a safe and effective option for TDT patients across diverse genotypes, including the most severe β0/β0.