bluebird bio presents new data on long-term transfusion independence and safety for LentiGlobin Gene Therapy for beta-thalassemia at ASH Meeting.

bluebird bio, Inc. announced new data from ongoing studies of LentiGlobin gene therapy for beta-thalassemia (betibeglogene autotemcel) in pediatric, adolescent and adult patients who have transfusion-dependent beta-thalassemia (TDT) , including results from the Phase III Northstar-3 (HGB-212) study in patients with a beta0/beta0 genotype or IVS-I-110 mutation, and the Phase III Northstar-2 (HGB-207) study in patients who do not have a beta0/beta0 genotype. These data, as well as updated results reflecting up to five years of follow-up from the completed Phase 1/II Northstar (HGB-204) study, were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida. As of the data cutoff presented 52 pediatric, adolescent and adult patients with TDT who do not have a beta0/beta0 genotype or have a beta0/beta0 genotype have been treated with LentiGlobin for beta-thalassemia in the Northstar, Northstar-2 and Northstar-3 studies.

TDT is a severe genetic disease caused by mutations in the beta-globin gene that result in reduced or significantly reduced hemoglobin (Hb). In order to survive, people with TDT maintain Hb levels through lifelong chronic blood transfusions. These transfusions carry the risk of progressive multi-organ damage due to unavoidable iron overload.

LentiGlobin for beta-thalassemia was designed to address the underlying genetic cause of TDT by adding functionalcopies of a modified form of the beta-globin gene (betaA-T87Q-globin gene) into a patient�s own hematopoietic (blood) stem cells (HSCs). bluebird bio�s clinical development program for LentiGlobin for beta-thalassemia includes studies across patient genotypes, including those who do not have a beta0/beta0 genotype, as well as those with a beta0/beta0 genotype.

�Blood transfusions, while necessary, result in unavoidable iron overload, which can cause multi-organ damage. These infusions also have an impact on patients and their families� lives,� said Ashutosh Lal, M.D., UCSF Benioff Children�s Hospital, Oakland, Calif. �It�s encouraging to see that adult, adolescent and pediatric patients with various genotypes in the LentiGlobin for beta-thalassemia clinical trials have achieved and continue to maintain transfusion independence.�

Northstar (HGB-204) Efficacy : As of June 12, 2019, data from up to five years (median 44.9; min�max: 34.8�61.3 months) of follow-up from the completed Phase 1/II Northstar (HGB-204) study show durable transfusion independence (TI) and stable HbAT87Q levels in patients who achieved TI. TI is defined as weighted average Hb beta 9 g/dL without red blood cell (RBC) transfusions for more than 12 months. Eight of 10 treated patients who did not have a beta0/beta0 genotype achieved and continued to maintain TI for up to 51.3 months as of the data cutoff, with a median weighted average Hb during TI of 10.3 g/dL. Transfusion volumes were reduced by 79% and 52% in the two patients who did not achieve TI. In patients who have a beta0/beta0 genotype (n=8), three of eight achieved and continued to maintain TI with a current duration up to 30.4 months as of the data cutoff, and a median weighted average Hb during TI of 9.9 g/dL. Among patients who achieved TI, a decrease in markers of iron burden, including liver iron concentration, serum ferritin and transferrin saturation, were observed over time. Liver iron concentrations began to decrease in eight of the 11 patients who achieved TI, with the largest decrease observed in patients who had 48 months of data available (n=7). A median 44% reduction (min�max: 17%�83%) was reported in these seven patients.

Northstar-2 (HGB-207) Efficacy : As of June 12, 2019, 21 of 23 patients were treated and have been followed for a median of 11.6 months. These patients ranged in age from 8 to 34 years, including six pediatric (<12 years and 15 adolescent adult greater than 12 years patients. three patients with more than 24 months of follow-up are enrolled in the long-term follow-up study ltf-303. ninety percent 9 10 of patients evaluable for ti had achieved it with median weighted average hb levels of 12.2 g dl minmax: 11.412.8 g dl during ti. all nine patients continued to maintain ti for a median duration of 15.2 months minmax: 12.121.3 months as of the data cutoff.ninety percent 18 20 of patients with at least five months of follow-up had not received a transfusion for at least 3.5 months and total hb was near normal in most with the median total hb at months 6 12 and 18 at 11.5 n="17)," 12.3 n="11)" and 12.2 g dl n="8)," respectively. hbat87q levels were stable over time: 8.7 g dl at month 6 9.3 g dl at month 12 and 9.4 g dl at month 18. in an exploratory analysis bone marrow from nine patients who had reached 12 months of follow-up and were transfusion independent was evaluated for myeloid to erythroid ratio. a low myeloid to erythroid ratio is a key feature of abnormal bone marrow rbc production that is characteristic of patients with tdt. in all nine patients an increase in the myeloid to erythroid ratio was observed suggesting improvement in bone marrow rbc production. a trend toward normalization of soluble transferrin receptor a marker of rbc production and reticulocyte counts a marker of hemolysis or rbc destruction was also observed. the trend toward normalization in rbc production supports the disease-modifying potential of lentiglobin for beta-thalassemia for patients with tdt.>

Northstar-3 (HGB-212) Efficacy : As of September 30, 2019, 13 patients (eight beta0/beta0, two beta0/IVS-I-110, three homozygous IVS-I-110 genotypes) were treated and had a median follow-up of 8.8 months (min�max: 2.5�20.0 months). Median age at enrollment was 17 years of age (min�max: 7�33 years); four patients were under 12 years of age. Two patients had at least 12 months of follow-up and were evaluable for TI. ?Both patients, one patient with a beta0/beta0 genotype and one pediatric patient with a beta0/IVS-I-110 genotype, achieved TI, and continued to maintain it with Hb levels of 13.2 g/dL and 10.4 g/dL, respectively, at last visit. In addition, nine of 11 patients with at least six months of follow-up did not receive a transfusion for more than three months as of last follow-up. In these patients, total Hb levels ranged from 8.3�14.2 g/dL at last visit.

LentiGlobin for beta-thalassemia Safety : Non-serious adverse events (AEs) observed during the HGB-204, HGB-207 and HGB-212 clinical studies that were attributed to LentiGlobin for beta-thalassemia were hot flush, dyspnoea, abdominal pain, pain in extremities, thrombocytopenia, leukopenia, neutropenia and non-cardiac chest pain. One serious adverse event (SAE) of thrombocytopenia was considered possibly related to LentiGlobin for beta-thalassemia for TDT. Additional AEs observed in clinical studies were consistent with the known side effects of HSC collection and bone marrow ablation with busulfan, including SAEs of veno-occlusive disease. With more than five years of follow-up to date, there have been no new unexpected safety events, no deaths, no graft failure and no cases of vector-mediated replication competent lentivirus or clonal dominance. In addition, there have been no new reports of veno-occlusive liver disease (VOD) as of the data cutoff presented at ASH.