Gene therapy reduces need for transfusions in beta-thalassemia

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LentiGlobin BB305 gene therapy reduced or eliminated the need for monthly transfusions among patients with transfusion-dependent beta-thalassemia, according to results from two phase 1/phase 2 clinical trials.“These study results exceeded our expectations with clinical benefit for nearly all patients and suggest that gene therapy may be an effective treatment for thalassemia in the future,” Alexis A. Thompson, MD, MPH, head of hematology at  Lurie Children’s Hospital of Chicago, said in a press release.

       Patients with transfusion-dependent beta-thalassemia — the most severe form of the disease — require long-term red cell transfusions for survival; however, risk for transfusion-related iron toxicity and infections remains high. Allogeneic hematopoietic stem cell transplantation serves as a possible curative option for beta-thalassemia, but use is limited by high risk for graft rejection, graft-versus-host disease and other toxicities.Previous research showed a patient with severe beta-thalassemia discontinued transfusions for more than 6 years once they achieved sustainable beta-globin expression after gene therapy with LentiGlobin BB305 .

            The FDA granted breakthrough therapy designation to the gene therapy product for the treatment of transfusion-dependent patients with beta-thalassemia major in 2015.Researchers evaluated the safety and efficacy of LentiGlobin BB305 among 22 patients aged 12 to 35 years with severe beta-thalassemia enrolled in the HGB-204 and HGB-205 studies — two nonrandomized, open-label trials initiated at various clinical sites in 2013.

           All patients were transfusion dependent and had various beta-thalassemia genotypes. Red cell infusions began at a median age of 3.5 years among patients in the HGB-204 study and when aged younger than 3 years among patients in the HGB-205 study.Researchers retrieved autologous CD34-positive cells from the patients, which were then transduced ex vivo with LentiGlobin BB305 vector — encoded adult hemoglobin with a T87Q amino acid substitution (HbAT87Q) — and reinfused after patients underwent IV myeloablative busulfan conditioning.

I                     n the HGB-205 study, patients underwent red cell hypertransfusion at least 3 months prior to stem cell mobilization and harvesting to ensure a hemoglobin level of at least 11 g/dL to enrich the hematopoietic stem cells in the harvested CD34-positive cells.