–Ongoing transfusion independence up to 3.5 years in patients with transfusion-dependent β-thalassemia (TDT); three patients have discontinued iron chelation –
–First patient with severe sickle cell disease (SCD) treated with gene therapy continues to show clinically meaningful improvement in symptoms of SCD and stable vector copy number and HbAT87Q in peripheral blood –
–Two recently treated patients with severe SCD show increasing levels of hemoglobin (HbAT87Q) and stable in vivo vector copy number (VCN) –
–Company to hold conference call and webcast today,
These data will be presented by
“HGB-205 was designed as a proof-of-concept study to initially assess
the feasibility of treatment with LentiGlobin gene therapy in patients
with TDT and severe SCD. Results from this study to date demonstrate the
potential for durable treatment effect of LentiGlobin, with stable HbAT87Q
production through 3.5 years of follow-up and sustained clinical
“We are beginning to see evidence of the long-term durability of benefit from treatment with LentiGlobin, with some TDT patients even transitioning off of chelation therapy,” said Prof. Cavazzana. “It is exciting to see the outcome in the patient with TDT with the longest follow-up in HGB-205, who has gone from years of regular transfusions to 3.5 years without a single blood transfusion after a one-time treatment with LentiGlobin gene therapy.”
Update on the First Patients with Severe Hemoglobinopathies Treated with LentiGlobin Gene Therapy (HGB-205) (Abstract P631)
Poster Session Date & Time:
Location: Poster area (Hall 7)
HGB-205 is an ongoing, open-label, single-center Phase 1/2 study
designed to evaluate the safety and efficacy of LentiGlobin drug product
in the treatment of patients with TDT and severe SCD. Four patients with
TDT and three patients with severe SCD have undergone infusion with
LentiGlobin drug product in this study as of
All patients with TDT have remained free of transfusions since shortly
after receiving LentiGlobin treatment. At last study visit:
- Patient 1201 (β0/βE genotype) has been free of transfusions for 41.9 months with total hemoglobin of 11.3 g/dL, of which 8.2 g/dL was HbAT87Q
- Patient 1202 (β0/βE genotype) has been free of transfusions for 38.7 months with total hemoglobin of 12.9 g/dL, of which 10.0 g/dL was HbAT87Q
- Patient 1206 (β0/βE genotype) has been free of transfusions for 20.3 months with total hemoglobin of 11.4 g/dL, of which 8.4 g/dL was HbAT87Q
- Patient 1203, who is homozygous for the severe β+ mutation IVS1-110, has been free of transfusions for 20.4 months with total hemoglobin of 8.3 g/dL, of which 6.6 g/dL was HbAT87Q
- All three patients with TDT and β0/βE genotype have discontinued iron chelation and transitioned to therapeutic phlebotomy.
- The safety profile continues to be consistent with autologous transplantation. No drug-product related adverse events (AEs) have been observed, and there is no evidence of clonal dominance.
Patient 1204 was 13 years old at enrollment. At last follow-up (31.7
months), this patient was producing 50% HbAT87Q – well
above the approximately 30% anti-sickling hemoglobin level predicted
to have potential clinical impact on the disease.
- Approximately 30 months post-treatment, Patient 1204 suffered an episode of acute gastroenteritis with vomiting and 2 days of fever up to 40°C (104°F), which was followed by a vaso-occlusive crisis (VOC) and subsequent hospitalization. His HbAT87Q and peripheral blood VCN levels have remained stable (HbAT87Q: 6.1 g/dL, VCN: 2.3 copies/diploid genome at 30 months), suggesting continued durability of the gene therapy.
- Patient 1207 was 16 years old at enrollment. At last follow-up (6.1 months), this patient was producing 20% HbAT87Q. This patient had a pre-treatment history of frequent episodes of VOC and acute chest syndrome (ACS) despite hydroxyurea prior to beginning regular transfusions and had one episode of ACS and a hospitalization at 6 months post-treatment.
- Patient 1208 was 21 years old at enrollment. At last follow-up (3.4 months), this patient was producing 15% HbAT87Q.
- The safety profile continues to be consistent with autologous transplantation. No gene therapy related AEs have been observed, and there is no evidence of clonal dominance.
bluebird bio will host a live webcast at
Transfusion-dependent β-thalassemia (TDT), also called β-thalassemia major or Cooley’s anemia, is an inherited blood disease that can be fatal within the first few years of life if not treated.
Despite advances in the supportive conventional management of the disease, which consists of frequent and lifelong blood transfusions and iron chelation therapy, there is still a significant unmet medical need, including the risk for significant morbidity and early mortality. Currently, the only advanced treatment option for TDT is allogeneic hematopoietic stem cell transplant (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft vs. host disease and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.
Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene that results in sickle-shaped red blood cells. Common complications include anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life and sometimes, early death.
Where adequate medical care is available, common treatments for patients with SCD largely revolve around prevention of infection and management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced treatment for SCD is allogeneic HSCT. Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, GvHD and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT.
About the HGB-205 Study
HGB-205 is an ongoing, open-label Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of subjects with TDT and SCD. The study enrolled seven subjects who will be followed to evaluate safety and transfusion requirements post-transplant. Among patients with sickle cell disease only, efficacy will also be measured based on the number of vaso-occlusive crises or acute chest syndrome events. For more information on the HGB-205 study, please visit clinicaltrials.gov using identifier NCT02151526.
About bluebird bio, Inc.
With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia, and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in 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. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTAL/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline.
bluebird bio has operations in Cambridge, Massachusetts, Seattle,
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia and severe sickle cell disease, including statements whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with transfusion-dependent ß-thalassemia and severe sickle cell disease and the potential long-term durable treatment effect of LentiGlobin. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, and the risk that any one or more of our product candidates will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the
Source: bluebird bio, Inc.