Our Product Pipeline
Beta-Thalassemia Product Development
Our LentiGlobin® product candidate aims to treat beta-thalassemia and sickle cell disease by inserting a fully functional human beta-globin gene into the patient's own hematopoietic stem cells. We have sponsored an ongoing Phase 1/2 clinical trial in France. Promising early clinical proof-of-concept results for one beta-thalassemia patient were reported in Nature in 2010. The subject remains transfusion-free 72+ months post-transplant, and one additional beta-thalassemia patient has subsequently been treated. The France trial is ongoing with the goal of enrolling additional beta-thalassemia patients and sickle cell disease patients.
In December 2013, we transplanted the first patient in a Phase 1/2 HGB-205 study in France. In March 2014, we initiated a Phase 1/2 study called the Northstar Study (HGB-204) in beta-thalassemia in the United States, Thailand and Australia. Information about the U.S. study is available on ClinicalTrials.gov or NorthstarStudy.com.
In June 2014, bluebird bio presented initial positive clinical safety and efficacy data from its HGB-205 clinical study at the 19th Annual Congress of the European Hematology Association (EHA). Clinical data were presented on two subjects (subjects 1 and 2), both with beta- thalassemia major and the Beta E/Beta 0 genotype who were treated using the new lentiviral vector BB305. To date, early and high production of βA-T87Q globin has resulted in rapid transfusion-independence at near-normal Hb levels in both patients, similar to what may be expected from a successful allogeneic transplant. Subjects 1 and 2 produced 6.6 g/dl of therapeutic βAT87Q-globin at 4.5 months and 4.2 g/dl of βAT87Q-globin at 2 months, respectively after receiving an autologous transplant. Subjects 1 and 2 received their last blood transfusion on day 10 and 12, respectively post-transplant and both subjects remain blood transfusion independent. No gene-therapy related adverse events have been observed to date. These preliminary data provide proof of principle that early transfusion independence can be achieved with gene therapy in beta-thalassemia major patients with B0/BE genotype. These preliminary data support the clinical relevance of the improvements bluebird bio has made to the lentiviral vector and to bluebird bio’s manufacturing process resulting in higher vector purity and potency. For a full report of the EHA data, click here.
Beta-thalassemia is one of the most common single-gene inherited conditions known throughout the world. It is an inherited blood disorder caused by a genetic abnormality of the beta-globin gene resulting in defective red blood cells, or RBCs. Genetic mutations cause the absence or reduced production of the beta chains of hemoglobin, or beta-globin, thereby preventing the proper formation of hemoglobin A, which normally accounts for greater than 95% of the hemoglobin in the blood of adults. Symptoms of beta-thalassemia can include severe anemia, splenomegaly, marrow expansion, bone deformities and iron overload in major organs. Patients with beta-thalassemia major (the most severe form of beta-thalassemia) receive chronic blood transfusion regimens aimed at maintaining a steady state of hemoglobin levels to treat their severe anemia. Chronic blood transfusions can be effective at preventing the hallmark symptoms of childhood beta thalassemia major, however, chronic transfusions introduce a large iron overload, which over time leads to mortality through iron-associated heart and liver toxicity. In order to prevent iron overload-associated risks, patients must adhere to daily iron chelation regimens. Poor compliance with chelation regimens remains a key challenge, and even with transfusion and iron chelation therapies, overall survival is significantly reduced.
The only potentially curative therapy for beta-thalassemia is allogeneic hematopoietic stem cell transplant (HSCT). However, because of the significant risk of transplant related morbidity and mortality, transplants are offered primarily only to pediatric patients with matched sibling donors, which occurs in less than 25% of all cases. Allogeneic HSCT carries a significant risk of morbidity and mortality related to serious infection, graft failure and graft-versus-host-disease.
For more information, please visit the links below, which are important resources for patients and their caregivers: