FDA Approves Beti-Cel in Transfusion-Dependent β-Thalassemia in Pediatrics and Adults

Betibeglogene Autotemcel for Transfusion-Dependent Beta-Thalassemia

Pediatric and adult patients who have β -thalassemia and need regular red blood cell infusions may now receive betibeglogene autotemcel, which has been approved by the FDA.

The FDA has approved betibeglogene autotemcel (beti-cel; Zynteglo) for adult and pediatric patients with β-thalassemia who need regular red blood cell infusions, according to a press release from the FDA.1

Patients will receive beti-cel as a 1 times gene therapy that is administered as a single dose. The approval comes after an FDA extension of the application review period by 3 months.2 The extension was needed for the FDA to review additional data submitted. While the data were a major amendment to the application, this did not impact safety.

“Beti-cel is a gene therapy for transfusion-dependent β-thalassemia. This product is the combination of the patient's autologous stem cells that have been transduced with a lentiviral vector that expresses the β-globin gene and allows for the production of normal human β-globin. This will allow for the production of hemoglobin A or normal adult hemoglobin which by and large patients with transmission-dependent thalassemia cannot make,” Alexis A. Thompson, MD, MPH, chief of the Division of Hematology, and Elias Schwartz, MD, Endowed Chair in Hematology at Children’s Hospital of Philadelphia, and a member of the American Society of Hematology (ASH) CONSA Steering Committee and former ASH president, said in an interview with CancerNetwork®.

Results from various trials relating to beti-cel’s efficacy in the indicated patient population supported the approval. Beti-cel was designed as one-time gene therapy to add functional copies of a modified form of the β-globin gene in hematopoietic stem cells. Once the gene is established, the hematopoietic stem cells may produce HbAT87Q which can eliminate or reduce the need for transfusions.


In the phase 3 HGB-207/Northstar-2 trial (NCT02906202), 20 out of 23 adult or pediatric patients with transfusion-dependent β-thalassemia and a non–β0/β0 genotype achieved transfusion independence (TI) with 6 patients being younger than 12.3 The average hemoglobin level during TI was 11.7 g/dL. The median duration of TI was 20.4 months, and at 12 months the average hemoglobin level was 8.7 g/dL.

Four patients experienced AEs relating to treatment. Grade 4 serious hepatic veno-occlusive disease was observed in 3 patients, and 1 had grade 2 nonserious hepatic veno-occlusive disease.


Following either the phase 1/2 HGB-205 (NCT02151526) or the phase 3 HGB-207 trials, patients were invited to enroll to the 13-year long-term LTF-303 study (NCT02633943).4

Achievement of transfusions independence occurred in 40 out of 51 patients, with rates of 68% in all patients treated on phase 1/2 trials and 86% in those on the phase 3 trials. At median post-infusion follow-up of 44.2 months, all patients who had TI remained free of transfusions. Median duration of ongoing TI was 57.1 months in those treated on phase 1/2 trials and 26.3 months in those on phase 3 trial.

Pediatric Studies

The phase 3 Northstar-2 and Northstar-3 (NCT03207009) studies included pediatric patients, of whom 16 were younger than 12 years and 11 were between 12 to 18 years of age. At a median follow-up of 25.5 months, TI was achieved in 91% of patients with a median weighted hemoglobin level during TI of 10.0 g/dL for those under 12 years and 11.7 g/dL for those 12 to 18 years.

The occurrence of AEs related to treatment was low in both studies, with 1 patient experiencing grade 3 thrombocytopenia post-infusion. No patients died during treatment.


  1. FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions. News Release. FDA. August 17, 2022. Accessed August 17, 2022. https://bit.ly/3Qv5KQd
  2. FDA extends decision dates on bluebird bio’s gene therapy drugs beti-cel and eli-cel by 3 months. News Release. January 18, 2022. Accessed August 11, 2022. https://bit.ly/3K2gFih
  3. 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(5):415-427. doi:10.1056/NEJMoa2113206
  4. Betibeglogene autotemcel (beti-cel) one-time tene Therapy for β-thalassemia continues to demonstrate durable efficacy across pediatric and adult patient populations and all genotypes in data presented at EHA2021 virtual. News Release. June 11, 2021. Accessed August 11, 2022. https://bit.ly/3vTk8JN

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