FDA Approves First Gene Therapy for Transfusion-Dependent Beta-Thalassemia

The Food and Drug Administration approved the first cell-based gene therapy for the treatment of transfusion-dependent beta-thalassemia (TDT) in pediatric and adult patients last Wednesday. Beta-thalassemia is a type of inherited blood disorder that causes a reduction of normal hemoglobin and red blood cells in the blood, leading to insufficient delivery of oxygen in the body.

The therapy, betibeglogene autotemcel (Zynteglo, bluebird bio), works by adding functional copies of a modified form of the beta-globin gene (β^A-T87Q-globin gene) into a patient’s own hematopoietic stem cells, allowing them to make normal to near normal levels of total hemoglobin without regular blood transfusions. The functional beta-globin gene is added into a patient’s cells outside of the body and then infused into the patient as a single-dose, one-time treatment.

The safety and effectiveness of betibeglogene autotemcel were established in two multicenter clinical studies that included adult and pediatric patients with TDT. Of 41 patients who received the therapy, 89% achieved transfusion independence (maintaining a pre-determined level of hemoglobin without needing any red blood cell transfusions for at least 12 months).

The most common adverse reactions associated with the therapy included reduced platelet and other blood cell levels. FDA noted in its approval that there is a potential risk of blood cancer associated with betibeglogene autotemcel; however, no cases have been seen in studies. Patients who receive the therapy should have their blood monitored for at least 15 years for any evidence of cancer. Patients should also be monitored for hypersensitivity reactions during therapy administration, for thrombocytopenia and for bleeding.

In the United States, betibeglogene autotemcel will cost $2.8 million. According to bluebird bio, the price reflects the therapy’s “robust and sustained clinical benefit” and its “potential to alleviate a lifetime of health care costs associated with regular RBC transfusions and iron management.” The company reported that patients with TDT require RBC transfusions every 2-5 weeks with lifetime health care costs than can reach $6.4 million in the U.S.