Our Product Pipeline
Beta-Thalassemia and sickle cell
Our LentiGlobin® product development program aims to treat beta-thalassemia and sickle cell disease by inserting a fully functional human ß-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 60+ 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. We also plan to initiate a Phase 1/2 study called the HGB-204 Study in beta-thalassemia in the United States in 2013.
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 ß-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 ß-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.
Sickle cell disease (SCD) is an inherited monogenic disease caused by a mutation in the ß-globin gene resulting in abnormal red blood cell function and chronic anemia. The disease is characterized by anemia, vaso-occlusive pain crisis, infections, stroke, overall poor quality of life and early death in a large subset of patients. Patients with severe SCD typically receive chronic blood transfusion regimens or hydroxyurea. As is the case with beta-thalassemia, chronic transfusions for SCD introduces the risk of iron overload, which over time leads to mortality through iron-associated heart and liver toxicity, and patients must adhere to daily iron chelation regimens. In controlled clinical studies, hydroxyurea has been shown to significantly reduce the burden of vaso-occlusive crisis and related complications, but does not eliminate them. In practice, many individuals with SCD find it difficult to adhere to hydroxyurea, in part because they cannot tolerate higher doses necessary to achieve optimal outcomes due to drug-related toxicities.
The only potentially curative therapy for SCD is allogeneic hematopoietic stem cell transplant (HSCT). Because of the significant risk of transplant related morbidity and mortality, transplants are offered primarily only to patients with available sibling matched donors. However, it is particularly difficult to find suitable donors for SCD patients of African descent, and it is estimated that only 10% of eligible patients are able to find such donors.