Betibeglogene Autotemcel Enables Transfusion-Independence for Patients With Beta-Thalassemia

Treatment with betibeglogene autotemcel enables transfusion independence for patients with transfusion-dependent beta (β)-thalassemia, according to results from the ongoing phase 3 Northstar-2 trial.

“Betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the β-globin (βA-T87Q) gene,” explained Franco Locatelli, MD, PhD, IRCCS Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome, and colleagues.

The Northstar-2 trial explored the efficacy and safety of betibeglogene autotemcel manufactured with the use of a refined process in adult and pediatric patients with transfusion-dependent β-thalassemia and a non–β0/β0 genotype.

A total of 23 patients were enrolled on the study and underwent myeloablation with busulfan and received intravenous betibeglogene autotemcel. The primary end point was transfusion independence, defined as a weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months.

The median follow-up was 29.5 months. Overall, 20 (91%) of 22 evaluable patients achieved transfusion independence. Of these patients who achieved transfusion independence, 6 were aged younger than 12 years.

Researchers noted that the average hemoglobin level during transfusion independence was 11.7 g per deciliter. Among patients who had transfusion dependence, the median level of gene therapy–derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) 12 months after receipt of betibeglogene autotemcel was 8.7 g per deciliter.

Adverse events considered by investigators to be related to betibeglogene autotemcel were reported in 4 patients. All events were considered non-serious, with the exception of thrombocytopenia in 1 patient. Overall, the safety profile of betibeglogene autotemcel was consistent with that of busulfan-based myeloablation.

“Treatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non–β0/β0 genotype, including those younger than 12 years of age,” concluded Dr Locatelli and colleagues.

Source:

Locatelli F, Thompson AA, Kwiatkowski JL, et al. Betibeglogene Autotemcel Gene Therapy for Non–β0/β0 Genotype β-Thalassemia. N Engl J Med. 2022; 386:415-427. doi:10.1056/NEJMoa2113206