Hemoglobinopathies

In an open-label phase 3 international multicenter study (ClinicalTrials.gov Identifier: NCT02906202) published in the New England Journal of Medicine, investigators evaluated the efficacy and safety of betibeglogene autotemcel (beti-cel) gene therapy in adult and pediatric patients with transfusion-dependent β-thalassemia and a non–β⁰/β⁰ genotype. Beti-cel contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (β^A-T87Q) gene. For the study, patients underwent myeloablation with busulfan and beti-cel was administered intravenously. The primary endpoint was transfusion independence (defined as a weighted average hemoglobin level of at least 9 g/dL without red-cell transfusions for 12 months or longer). A total of 23 patients were treated with beti-cell. They were evaluated over a median follow-up period of 29.5 months. Among 22 evaluable patients, 20 (91%) achieved transfusion independence, including 6 of 7 (86%) who were younger than 12 years of age. During the period of transfusion independence, the average hemoglobin level was 11.7g/dL. The safety profile of beti-cel was consistent with that of busulfan-based myeloablation. Four patients had at least 1 adverse event (AE) considered to be related or possibly related to beti-cel; all AEs were nonserious, with the exception of thrombocytopenia in 1 patient. No cases of cancer were observed. This study was funded by Bluebird Bio. An excellent visual abstract is included online.