Our Product Pipeline
Beta-Thalassemia Product Development
Our LentiGlobin® BB305 product candidate aims to treat beta-thalassemia and sickle cell disease by inserting a functional human beta-globin gene into the patient's own hematopoietic stem cells ex vivo and then transplanting those modified cells into the patient through infusion into the bloodstream, also known as autologous stem cell transplantation. LentiGlobin BB305 drug product is currently used in two Phase 1/2 studies for the treatment of beta-thalassemia: the Northstar Study (HGB-204) in the United States, Australia and Thailand, and HGB-205 in France. Information about the U.S. study is available on ClinicalTrials.gov or NorthstarStudy.com.
In December 2014, we presented data from our Northstar and HGB-205 studies at the 56th Annual Meeting of the American Society of Hematology (ASH) that further supported the initial positive clinical safety and efficacy data from our HGB-205 clinical study presented at the 19th Annual Congress of the European Hematology Association (EHA) in June 2014. The data presented at ASH include the first five subjects treated in the ongoing Phase 1/2 Northstar Study and the first three subjects from our HGB-205 study. These studies include the first subjects with the beta-0/beta-0 genotype of beta-thalassemia treated with LentiGlobin BB305 drug product and the first subject with sickle cell disease treated with gene therapy.
The Northstar Study is an ongoing, open-label, single-dose, international, multicenter Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product for the treatment of subjects with beta-thalassemia. As of December 1, 2014, five subjects with beta-thalassemia have undergone infusion with LentiGlobin BB305 drug product in the Northstar Study. The first two treated subjects are producing steadily increasing amounts of vector derived hemoglobin and have been free from the need for transfusions for the past five months and three months, respectively. These patients have stable hemoglobin of 8.6 g/dL and 9.6 g/dL at six months and three months post-treatment, respectively. They are producing 3.8 g/dL and 6.8 g/dL of vector derived hemoglobin, which represents 44% and 71% of total hemoglobin, respectively. Three additional subjects have been infused, but it is too early to draw any meaningful conclusions on clinical efficacy.
HGB-205 is an ongoing, open-label, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with beta-thalassemia and sickle cell disease. As of December 1, 2014, two subjects with beta-thalassemia have undergone infusion with LentiGlobin BB305 drug product. Both subjects achieved rapid transfusion independence with near-normal hemoglobin levels of 11.0 g/dL and 13.4. g/dL, similar to what may be expected from a successful allogeneic transplant, and remain free from the need for transfusions at 12 months and six months post-transplant, respectively. They are producing 7.7 g/dL and 9.6 g/dL of vector derived hemoglobin, which represents 70% and 72% of total hemoglobin, respectively. The third patient, the first patient with sickle cell disease to be treated with gene therapy, has achieved neutrophil engraftment, but it is too early post-transplant to draw any meaningful conclusions on clinical efficacy.
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: