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.
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.