– Majority (12/13) of patients with non-β0/β0 genotypes were transfusion-free at median 27 months following LentiGlobin treatment –
Interim results also showed that all but one patient with a non-β0/β0
genotype (12 of 13 patients) stopped receiving regular red blood cell
“These interim data demonstrate the potential of LentiGlobin gene
therapy to address the underlying genetic cause of TDT and increase
production of functional red blood cells,” said
“We look forward to our first filing in the
Transfusion-dependent thalassemia is a severe genetic disease characterized by reduced or absent hemoglobin production that results in severe anemia and ineffective red blood cell production. People with TDT need regular blood transfusions to survive, but chronic transfusions lead to unavoidable iron overload that can result in multi-organ damage and shortened life span.
“One-time treatment with LentiGlobin gene therapy resulted in positive
outcomes for patients with TDT, with the majority of the 22 patients in
the two Phase 1/2 studies followed for two years or longer maintaining
independence from transfusion without unexpected or unmanageable side
effects,” said Dr.
Interim Efficacy Results of the Northstar and HGB 205-Studies
The recently completed Northstar study (HGB-204) is an open-label, single-dose, non-randomized, multi-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin for the treatment of patients with TDT. HGB-205 is an ongoing, open-label, single-dose, non-randomized, single-center Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin for the treatment of patients with TDT and severe sickle cell disease (SCD).
At baseline, all 13 patients with non-β0/β0
genotypes were transfusion-dependent. With a median time since last
transfusion of 27 months (range: 11-42 months), all but one of these
13 patients had stopped receiving regular
RBCtransfusions. These patients had a median level of gene therapy-derived hemoglobin (known as HbAT87Q) of 6.0 (3.4-10.0) g/dL and total hemoglobin of 11.2 (8.2-13.7) g/dL at the last study visit (12 to 36 months post-treatment).
- At baseline, all nine patients with genotypes that completely or nearly completely eliminate production of functional adult hemoglobin (β0/β0 genotypes or IVS1-110/IVS1-110 genotype) were transfusion-dependent. Three of these patients had stopped regular transfusions, with 14, 14 and 21 months having elapsed since their last transfusions, respectively. At the most recent study visit (12 to 30 months), these patients had 8.2, 6.8 and 6.6 g/dL HbAT87Q and 9.0, 10.2 and 8.3 g/dL total hemoglobin, respectively.
The six remaining patients with β0/β0 genotypes
continued to receive
RBCtransfusions; they had a median of 4.2 (0.3-8.7) g/dL HbAT87Q at last study visit. All but one of these patients had clinically meaningful reductions in the number and volume of transfusions compared with the two years prior to study enrollment.
Additionally, in the HGB-205 study, after the four patients with TDT
Interim Safety Results of the Northstar and HGB 205-Studies
The safety profile of LentiGlobin in TDT continues to be consistent with myeloablative conditioning with the chemotherapy agent busulfan. In the Northstar study, five mild adverse events (AEs), all Grade 1, were characterized as possibly or probably related to LentiGlobin. Nine serious adverse events (SAEs) were reported, including two episodes of veno-occlusive liver disease; none were considered related to LentiGlobin. In HGB-205, there were three SAEs, all Grade 2 or 3. For both studies, all adverse events were treated with standard measures. There was no evidence of a single gene clone becoming dominant or of any patient developing a replication-competent strain of the viral vector. All patients who were engrafted survived.
About the Northstar (HGB-204) Study
The recently completed Phase 1/2 Northstar study is an open-label, single-dose, non-randomized, multi-center study conducted in
About the HGB-205 Study
The Phase 1/2 HGB-205 study is being conducted at a single site in
The principal investigator of the HGB-205 study is Marina Cavazzana,
M.D., Ph.D., Professor of Hematology at
Dr. Leboulch and his team led the development of the HbAT87Q LentiGlobin vector.
bluebird bio is developing LentiGlobin with a goal of filing for regulatory approval in
LentiGlobin was granted Orphan Drug status by the
Transfusion-dependent β-thalassemia (TDT) is a severe genetic disease characterized by reduced or absent hemoglobin levels that results in severe anemia and ineffective red blood cell production. 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.
Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only available option to address the underlying genetic cause of TDT, though it carries significant risks. Complications of allogeneic 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 allogeneic HSCT.
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 for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ product candidate for the treatment of transfusion-dependent β-thalassemia, also known as β-thalassemia major, 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 programs, bb2121 and bb21217, are anti-BCMA CAR T programs partnered with
bluebird bio has operations in
LentiGlobin and Lenti-D are trademarks 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 research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia and severe sickle cell disease. 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 or planned 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, and the risk that any one or more of our product candidates, including our bb2121 product candidate, 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-K, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the
Source: bluebird bio, Inc.