Drug product attributes predict clinical efficacy in betibeglogene autotemcel gene therapy for β-thalassemia

Ex vivo autologous hematopoietic stem cell lentiviral-based gene therapy with betibeglogene autotemcel has been studied in patients with transfusion-dependent β-thalassemia in Phase III clinical trials (HGB-207 and HGB-212), with 90% of patients reaching transfusion independence (TI). Here, we explore manufacturing parameters, drug product quality attributes, and limited patient characteristics that had an impact on clinical efficacy in HGB-207 and HGB-212. Retrospective analysis revealed that the peripheral blood vector copy number (VCN) was related to TI, with a strong correlation between peripheral blood VCN at 6 months and gene therapy–derived therapeutic protein (HbAT87Q) expression at 6 months (correlation coefficient, 0.8681; p