Results of Phase III trials NORTHSTAR-2 and NORTHSTAR-3 of LentiGlobin gene therapy to treat transfusion-dependent beta-thalassemia. bluebirdbio.

bluebird bio, Inc. announced new data from the Phase III Northstar-2 (HGB-207) and Northstar-3 (HGB-212) clinical studies of its investigational LentiGlobin gene therapy in the treatment of patients with transfusion-dependent beta-thalassemia (TDT) at the 60th Annual Meeting of the American Society of Hematology (ASH).

Northstar-2 (HGB-207) Efficacy: After treatment with LentiGlobin, patients are monitored for production of HbAT87Q, which is gene therapy derived-hemoglobin. The production of HbAT87Q increases the overall hemoglobin level in patients with the goal of reducing or eliminating the need for transfusions. Sixteen patients with non-?0/?0 genotypes (aged 8 � 34 years); two pediatric and 14 adolescents/adults with TDT have been treated in the Phase 3 Northstar-2 study as of September 14, 2018, the data cut-off date. Eleven of these patients had at least three months of follow-up available at the data cut-off. Ten of the 11 patients had stopped receiving transfusions and had hemoglobin levels of 11.1 � 13.3 g/dL at the time of the last study visit (3 � 18 months post-treatment). HbAT87Q levels in these 10 patients ranged from 7.7 � 10.6 g/dL and significantly contributed to total hemoglobin (67 � 92 percent). An exploratory analysis was conducted with bone marrow from six patients with 12 months of follow-up after treatment. The samples were evaluated for cellularity and myeloid to erythroid ratio. A low myeloid to erythroid ratio is a key feature of dyserythropoesis, or abnormal bone marrow red blood cell production, characteristic of patients with TDT. In five patients, all of who had stopped chronic transfusions, an increase in the myeloid to erythroid ratio was observed, suggesting improvement in red blood cell production.

Northstar-3 (HGB-212) Efficacy : As of September 14, 2018, three patients with TDT and a ?0/?0 genotype or an IVS-I-110 mutation had been treated with LentiGlobin in the Phase III Northstar-3 study. All three patients, as of November 19, 2018, had total hemoglobin of greater than 10 g/dL at their last assessment, including a pediatric patient. Patient 1 had no transfusions following LentiGlobin treatment and their last assessment at month 12, Patient 2 had their last transfusion 1.9 months post-treatment and last assessment at month six, Patient 3 had their last transfusion at 1.4 months post-treatment and last assessment at month three.

Northstar-2 and Northstar-3 Safety: In the Northstar-2 and Northstar-3 studies the safety profile of LentiGlobin gene therapy remained generally consistent with myeloablative busulfan conditioning, including serious adverse events (SAEs) of vaso-occlusive liver disease. One SAE of grade 3 thrombocytopenia was reported and considered possibly related to LentiGlobin. As of the data cut-off date, September 14, 2018, a total of 37 pediatric, adolescents and adult patients with TDT and a non-?0/?0 or ?0/?0 genotype, including patients with IVS-I-110 mutations, have been treated with LentiGlobin in the Northstar, Northstar-2 and Northstar-3 studies.