First presentation of data from patients with a β0/β0 genotype and a pediatric patient treated with LentiGlobin in Phase 3 Northstar-3 study both have stopped chronic blood transfusions
10 of 11 patients with non-β0/β0 genotypes and more than three months follow-up have stopped chronic transfusions in Phase 3 Northstar-2 study
Indicators of poor red blood cell production appear corrected in exploratory analysis of bone marrow following treatment with LentiGlobin
“Our new data for LentiGlobin in transfusion-dependent β-thalassemia
includes a broader population of patients with both non-β0/β0
and β0/β0 genotypes, as well as our first
pediatric patients. In all of these patients we observed improved
hemoglobin levels and reduced or eliminated requirements for blood
transfusions following treatment with LentiGlobin,” said
TDT is an inherited blood disorder caused by a mutation in the β-globin gene, which causes ineffective red blood cell production leading to severe anemia. People with TDT require regular transfusions to maintain hemoglobin (Hb) levels in order to survive, but chronic transfusions carry risks, including iron overload that can result in multi-organ damage and shortened life expectancy.
“In my practice, I see the serious complications of
transfusion-dependent β-thalassemia and the everyday toll this disease
takes on my patients and their families,” said Professor
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-β0/β0 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
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
All three patients, as of
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,
For more information about the ongoing clinical studies of LentiGlobin in TDT visit www.northstarclinicalstudies.com or clinicaltrials.gov and use identifier NCT02906202 for Northstar-2 (HGB-207) and NCT03207009 for Northstar-3 (HGB-212).
About Transfusion-Dependent β-Thalassemia
TDT is an inherited blood disorder caused by a mutation in the β-globin gene, which causes ineffective red blood cell production leading to severe anemia. Supportive care for people with TDT consists of a lifelong regimen of chronic blood transfusions to enable survival and suppress symptoms of the disease, and iron chelation therapy to manage iron overload that results from the transfusions.
Despite the availability of supportive care, many people with TDT experience serious complications and organ damage due to underlying disease and iron overload. By eliminating or reducing the need for blood transfusions, the long-term complications associated with TDT may be reduced.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been successfully used to treat TDT and is currently the only available option with the potential to correct the genetic deficiency in TDT. Complications of allo-HSCT include a risk of treatment-related mortality, graft failure, graft-versus-host disease (GvHD) and opportunistic infections, particularly in patients who undergo non-sibling matched allo-HSCT.
LentiGlobin is a one-time gene therapy being studied as a potential treatment to address the underlying genetic cause of TDT, which could eliminate or reduce the need for blood transfusions.
bluebird bio’s clinical development program for LentiGlobin includes
ongoing studies around the world with sites
in Australia, Germany, Greece, France, Italy, Thailand, the United
Kingdom and the
In addition, bluebird is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for TDT and sickle cell disease.
The EMA previously granted Priority Medicines (PRIME) eligibility and Orphan Medicinal Product designation to LentiGlobin for the treatment of TDT. LentiGlobin is also part of the EMA’s Adaptive Pathways pilot program, which is part of the EMA’s effort to improve timely access for patients to new medicines.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built a pipeline with broad potential application in severe genetic diseases and cancer.
bluebird bio's gene therapy clinical programs include investigational treatments for cerebral adrenoleukodystrophy, transfusion-dependent β-thalassemia and sickle cell disease.
bluebird bio's oncology pipeline is built upon the company's lentiviral
gene delivery and T cell engineering, with a focus on developing novel T
cell-based immunotherapies, including chimeric antigen receptor (CAR T)
and T cell receptor (TCR) therapies. The company’s lead oncology
programs are anti-BCMA CAR T programs partnered with
bluebird bio’s discovery research programs include utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company's pipeline.
bluebird bio has operations in
LentiGlobin is a trademark of bluebird bio, Inc.
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s views with respect to the potential for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia, and the Company’s expectations regarding the review, potential regulatory approval and potential commercial launch of its LentiGlobin product candidate in
Source: bluebird bio, Inc.