bluebird bio’s ZYNTEGLO™ (autologous CD34⁺ cells encoding β A-T87Q-globin gene) will be the first gene therapy to treat transfusion-dependent β-thalassemia if approved.

Transfusion-dependent β-thalassemia (TDT) is a genetic disease resulting from mutations in the β-globin gene. The mutations lead to negatively impact hemoglobin production, which can be reduced or completely absent. As a result, patients suffering from TDT require regular blood transfusions throughout their lifetimes, which can cause progressive multi-organ damage due to iron overload, which is managed to some extent with daily iron chelation therapy.

People in Europe with TDT may have a new treatment option soon. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recently recommended conditional marketing authorization for bluebird bio’s ZYNTEGLO™ (autologous CD34⁺ cells encoding the β A-T87Q-globin gene; previously LentiGlobin™) gene therapy for patients 12 years and older with TDT who do not have a β₀/β₀ genotype and for whom hematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related hematopoietic stem cell (HSC) donor is not available.

The new gene therapy adds functional copies of a modified form of the β-globin gene (β A-T87Q-globin) into a patient’s own HSCs, avoiding the need for allogeneic HSC transplantation (allo-HSCT) of donor HSCs from another person. Apheresis is used to collect the patient’s HSCs, into which a lentiviral vector carrying the β A-T87Q-globin gene is then inserted. The patient receives chemotherapy to prepare his/her bone marrow for the modified HSCs, which are then administered via infusion. After treatment and incorporation of the β A-T87Q-globin gene, the patient has the potential to produce HbAT87Q, a form of hemoglobin, in quantities sufficient to reduce or eliminate the need for transfusions.

ZYNTEGLO was reviewed under an accelerated assessment timeline as part of the EMA’s Priority Medicines (PRIME) and Adaptive Pathways programs. The CHMP’s recommendation was based on data from phase I/II, III and long-term follow-up studies. The European Commission will review the CHMP’s decision and determine whether it will grant marketing authorization for ZYNTEGLO in the European Union (EU), with a decision expected in the second quarter of 2019.