Betibeglogene autotemcel

Betibeglogene autotemcel is an autologous gene therapy that adds functional copies of the β-globin (HBB) gene to hematopoietic stem cells to treat β-thalassemia. β-thalassemia is a hereditary disease caused by more than 200 mutations in HBB, a gene responsible for encoding the β-subunit of hemoglobin A. In patients with β-thalassemia, β-globin production is abolished (β0) or reduced (β+), leading to intracellular hemichrome precipitation, ineffective erythropoiesis, chronic hemolysis, and profound anemia. Long-term red cell transfusions are needed for survival and the prevention of serious complications in patients with the most severe form of this disease.

Betibeglogene autotemcel is a gene therapy consisting of autologous CD34+ cells. A patient’s hematopoietic stem cells are collected and enriched for CD34+ cells and transduced ex vivo with BB305 LVV, a self-inactivating lentiviral vector (LVV). BB305 LVV has a functional copy of HBB with an amino acid substitution of threonine (T) to glutamine (Q) at position 87 (βA-T87Q-globin). After betibeglogene autotemcel is infused into a patient, CD34+ hematopoietic stem cells engraft in the bone marrow and differentiate to produce βA-T87Q-globin that will combine with α-globin to form functional hemoglobin A. The expression of βA-T87Q-globin corrects the imbalance between α- and β-globin in patients with β-thalassemia, and may lead to normal hemoglobin levels. The use of betibeglogene autotemcel has the potential to eliminate the need for red blood cell transfusions.