In March, Bluebird Bio received a positive opinion for its gene therapy Zynteglo for β-thalassemia from the European Medicines Agency’s advisory body. The next step, approval by the European Commission, is expected this summer. If approved, Zynteglo will be the first gene therapy approval for thalassemia. The recent decision from the agency’s Committee for Medicinal Products for Human Use was based on data from several clinical trials, in which 37 patients in total received gene-modified cells. The therapy removes bone marrow cells from the patient and transduces the CD34+ hematopoietic stem cells ex vivo with a BB305 lentiviral vector encoding a functional modified β-globin gene (βA-T87Q) under the control of the β-globin enhancer and locus control region. With the modified bone marrow cells, the body can produce functional hemoglobin, which can reduce or eliminate the need for transfusions. Patients with thalassemia, who experience severe anemia due to a mutation in their globin gene, can be treated with bone marrow transplants, but only from HLA-matched donors, which leaves many unable to receive this therapy. Absent that, patients need frequent blood transfusions, which can lead to iron overload and result in organ damage. In the phase 1/2 Northstar trial of ten patients, eight had been transfusion free for a median of 38 months at the conclusion of the trial. Yet to be announced is the likely price tag for Zynteglo. Based on other one-time curative gene therapies, such as Luxturna (Nat. Biotechnol. 36, 291–292, 2018), it is likely to be in the six figures. However, Bluebird floated the idea of annual installments in January at the J.P. Morgan Healthcare Conference. Shortly after, a rival company Sangamo announced their first results in thalassemia using their ex vivo gene editing protocol for a single patient with the most severe form of the disease.
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Thalassemia gene therapy nears approval. Nat Biotechnol 37, 493 (2019). https://doi.org/10.1038/s41587-019-0130-2
Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics
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