The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of the first gene therapy for transfusion-dependent β-thalassemia (TDT), a rare inherited blood condition that causes chronic severe anemia. Autologous CD34+ cells encoding β A-T87Q-globin gene (Zynteglo, Bluebird Bio) is for people 12 years and older with TDT who do not have a β0/β0 genotype, for whom hematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen–matched related HSC donor is not available. TDT is a severe genetic disease caused by mutations in the β-globin gene that result in reduced or absent hemoglobin, necessitating lifelong blood transfusions and iron chelation therapy. "The goal of treatment with Zynteglo is to enable patients with transfusion-dependent β-thalassemia to produce hemoglobin at sufficient levels to allow lifelong independence from blood transfusions," David Davidson, MD, chief medical officer, Bluebird Bio, said in a news release. "The positive CHMP opinion for Zynteglo is a crucial step toward providing what would be the first one-time gene therapy for people living with TDT." Using a lentiviral viral vector, Zynteglo (formerly called LentiGlobin) adds functional copies of a modified β-globin gene into a patient's own stem cells, thereby addressing the underlying genetic cause of the disease. In multiple clinical trials of patients with TDT without a β0/β0 genotype, the majority who were treated with Zynteglo achieved transfusion independence and maintained a hemoglobin of 9 g/dL or higher. The most common side effects were thrombocytopenia, abdominal pain, non-cardiac chest pain, pain in the extremities, dyspnea, and hot flush. Zynteglo should only be administered in a qualified treatment center by a physician with experience in stem cell transplantation and in the treatment of patients with β-thalassemia. Zynteglo had orphan drug designation and received priority review since it addresses an unmet medical need, the EMA said. The positive CHMP opinion will now be reviewed by the European Commission, which will make the final decision on marketing authorization in the European Union. A final decision is expected in the second quarter of 2019. Source
