Hemoglobinopathies

At the 63rd Annual Meeting of the American Society of Hematology (ASH), results of a multicenter, international trial of the ex vivo gene therapy betibeglogene autotemcel (beti-cel) indicate it is potentially curative for transfusion-dependent beta thalassemia (TDT), due to its ability to yield near-normal hemoglobin levels and thus transfusion independence (TI). The developer of beti-cel, bluebird bio Inc, describes it as one-time gene therapy that adds functional copies of a modified β-globin gene (βA-T87Q-globin gene) into a patient's own hematopoietic stem cells. In 2 completed phase 1/2 studies (HGB-204, HGB-205) and 2 ongoing phase 3 studies (HGB-207, HGB-212), a total of 63 patients with TDT were treated with beti-cel, and after 2 years of follow-up, they could enroll in the long-term follow-up study TF-303 (ClinicalTrials.gov Identifier: NCT02633943) for up to 13 years. At ASH, investigators reported results from LTF-303 in patients with up to 7 years of follow-up. As of March 9, 2021, LTF-303 had 51 enrolled patients (22 from phase 1/2 trial, 29 from phase 3 trial, 55% female, median age 19 years). Median postinfusion follow-up was 44.2 months. A total of 40 patients achieved TI and all had reductions in iron burden over time. No beti-cel–related AEs were observed after 2 years postinfusion. No deaths, replication-competent lentivirus, insertional oncogenesis, or malignancies were reported. The authors concluded, "Sustained levels of HbAT87Q and effective restoration of iron homeostasis over time reduced iron management burden in [patients] treated with beti-cel."