Positive Interim Data Published for Transfusion-Dependent Β-Thalassemia Gene Therapy

Drug company bluebird bio, Inc, has announced the publication of positive interim data for its gene therapy to eliminate or reduce chronic blood transfusions in patients with transfusion-dependent β-thalassemia (TDT).

TDT, a severe genetic disease caused by mutation in the HBB gene, is characterized by reduced or absent hemoglobin levels that result in severe anemia treated with lifelong, chronic blood transfusions to enable survival and control the symptoms of the disease. Allogenic hematopoietic stem cell transplantation is the only option currently available to address the genetic cause of β-thalassemia, but donor availability and transplantation-related risk limit the broad use of this therapeutic approach.

The therapy, which bluebird bio proposes to market as LentiGlobin, uses a lentiviral transfer of a marked β-globin, and is also being investigated for potential use in patients with sickle cell disease.

The study results, published in The New England Journal of Medicine, are from two phase 1 and 2 studies in which researchers obtained mobilized autologous CD34+ cells from 22 patients with TDT and transduced the cells ex vivo with LentiGlobin BB305 vector. After patients underwent myeloablative busulfan conditioning, the cells were reinfused into the patients.

At a median of 26 months (range, 15-42) after infusion of the gene-modified cells, in 9 patients with a β⁰/β⁰ genotype (which results in 0% relative percentage of adult hemoglobin), the median annualized transfusion volume was decreased by 73%, and 3 patients were able to discontinue transfusions entirely. In 13 patients with a non—β⁰/β⁰ genotype, all but 1 were able to discontinue transfusions.

Treatment-related adverse events were consistent with those associated with autologous stem-cell transplantation, and no clonal dominance related to vector integration was observed.

“These interim data demonstrate the potential of LentiGlobin gene therapy to address the underlying genetic cause of TDT and increase production of functional red blood cells,” said Dave Davidson, MD, chief medical officer of bluebird bio, in a statement. “We hope the refined manufacturing process implemented in our ongoing pivotal trials of LentiGlobin will translate into further normalization of total hemoglobin levels across genotypes.”

bluebird bio says that it plans to file for regulatory approval of the drug in the European Union this year.

Reference

Thompson AA, Walters MC, Kwiatkowski J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. NEJM. 2018;378:1479-1493. doi: 10.1056/NEJMoa1705342.