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

ABSTRACT: 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 (HbA^T87Q) expression at 6 months (correlation coefficient, 0.8681; p < 0.0001; R²

SUBMITTER: Whitney D 

PROVIDER: S-EPMC10709156 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature