– Majority (12/13) of patients with non-β0/β0
genotypes were transfusion-free at median 27 months following
LentiGlobin treatment –
bluebird bio, Inc. (Nasdaq: BLUE) today announced interim data
published in the New England Journal of Medicine (NEJM) from two
separate two-year clinical studies investigating the potential for
LentiGlobin™ gene therapy to eliminate or reduce chronic blood
transfusions in patients with transfusion-dependent β-thalassemia
(TDT). Both studies, Northstar (HGB-204), which recently was
completed, and HGB-205, which is ongoing, are evaluating the safety
and efficacy of one-time treatment with LentiGlobin gene therapy
and the interim results showed that a majority of the 22 patients
in the two Phase 1/2 studies followed for two years or longer
remained free from transfusions.
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 (RBC) transfusions, with a median time since last
transfusion of 27 months. In the nine patients with a β0/β0
genotype or similar severity, median transfusion volume decreased
by 73 percent, and RBC transfusions were stopped in three patients.
Treatment with LentiGlobin requires an autologous stem cell
transplant. The safety profile of LentiGlobin has been consistent
with myeloablative conditioning with the chemotherapy agent
busulfan.
“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 Dave
Davidson, M.D., chief medical officer, bluebird bio. “Nearly all
patients in the two studies with a non-β0/β0 genotype achieved
freedom from chronic blood transfusions and, importantly, several
of these patients reached normal or near-normal total hemoglobin
levels and sustained those levels throughout the interim study
period. We hope the refined manufacturing process implemented in
our ongoing pivotal trials of LentiGlobin will translate into
further normalization of total hemoglobin levels across
genotypes.”
“We look forward to our first filing in the European Union (EU)
this year and continue to work closely with investigators and
regulatory authorities to complete our trials and bring this
important treatment option to patients as soon as possible,” said
Davidson.
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. Alexis Thompson, Head of
Hematology and Director of the Comprehensive Thalassemia Program at
Ann & Robert H. Lurie Children’s Hospital of Chicago, and
Professor of Pediatrics at Northwestern University Feinberg School
of Medicine and one of the lead authors of the NEJM paper. “People
with TDT cannot make enough hemoglobin in their red blood cells and
rely on frequent transfusions to survive, which can cause serious
complications. Most will not have a suitable donor for conventional
allogeneic stem cell transplant. These results suggest that gene
therapy could become an effective treatment for TDT.”
Interim Efficacy Results of the Northstar and HGB
205-StudiesThe 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).
Through June 2, 2017, 18 patients (ages 12 to 35) in the
Northstar study, and four patients with TDT (ages 16 to 19) in
HGB-205 had received LentiGlobin. Ten of the 18 patients in the
Northstar study and three of the four patients in HGB-205 have
non-β0/β0 genotypes. One patient in HGB-205 is homozygous for the
IVS1-110 mutation and has a severe clinical presentation similar to
that seen in β0/β0 genotypes. Interim results published in NEJM
from all 22 patients with TDT in the two studies showed:
- 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 RBC
transfusions. 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 RBC transfusions; 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 ceased RBC transfusions following LentiGlobin therapy, the
degree of hemolysis fully corrected in two patients by
36 months after treatment. After treatment with LentiGlobin,
three patients with non-β0/β0 genotypes were able to transition to
therapeutic phlebotomy (in which 200 ml of blood was withdrawn each
month) to reduce the iron overload they had developed from chronic
RBC transfusions. In these three patients, blood hemoglobin levels
were stable despite a cumulative phlebotomy volume of over 1 liter
per patient. One patient no longer had evidence of clinically
meaningful iron overload and stopped receiving both iron chelation
therapy and therapeutic phlebotomy.
Interim Safety Results of the Northstar and HGB
205-StudiesThe 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) StudyThe recently completed
Phase 1/2 Northstar study is an open-label, single-dose,
non-randomized, multi-center study conducted in the United States,
Australia and Thailand. It was designed to evaluate the safety and
efficacy of LentiGlobin in increasing hemoglobin production and
eliminating or reducing transfusion dependence in subjects with
transfusion dependent beta-thalassemia. The study treated 18 adults
and adolescents who are being followed to evaluate safety and
efficacy post-LentiGlobin infusion. For more information on the
Northstar study, please visit www.northstarstudy.com or
clinicaltrials.gov using identifier NCT01745120.
About the HGB-205 StudyThe Phase 1/2 HGB-205 study is
being conducted at a single site in France. It is designed to
evaluate the safety and efficacy of LentiGlobin in the treatment of
subjects with TDT and SCD. The study has enrolled seven subjects.
Efficacy in subjects with TDT includes evaluation of transfusion
requirements post-treatment and level of hemoglobin. For patients
with SCD, efficacy is being measured based on the number of
vaso-occlusive crises or acute chest syndrome events pre- and
post-treatment. For more information on the HGB-205 study, please
visit clinicaltrials.gov using identifier NCT02151526.
The principal investigator of the HGB-205 study is Marina
Cavazzana, M.D., Ph.D., Professor of Hematology at Paris Descartes
University, Director Biotherapy Department, Necker Hospital, AP-HP,
and Co-director of the Human Lympho-hematopoiesis Inserm laboratory
at Imagine Institute for Genetic Diseases, Paris, France, in
collaboration with Philippe Leboulch, M.D., Professor of Medicine
at the University Paris-Sud and High Counselor and Honorary
Scientific Director at France’s Commissariat à l’énergie atomique
et aux énergies alternatives (CEA) and visiting faculty at Harvard
Medical School in the Genetics Division of Brigham & Women’s
Hospital, Boston, MA. Dr. Leboulch was a scientific founder of
bluebird bio and serves as the co-chairman of its Scientific
Advisory Board.
Dr. Leboulch and his team led the development of the HbAT87Q
LentiGlobin vector.
About LentiGlobinbluebird bio is developing LentiGlobin
with a goal of filing for regulatory approval in the United States
and the EU for TDT and for severe SCD. The company is currently
conducting four ongoing clinical studies of LentiGlobin with a
fifth that has recently completed. Studies currently ongoing
include HGB-205, a single center Phase 1/2 study in both TDT and
SCD; Northstar-2 (HGB-207) and Northstar-3 (HGB-212), both
multi-center, international Phase 3 studies for the treatment of
patients with both non-β0/β0 and β0/β0 TDT genotypes, respectively;
and HGB-206, a multicenter Phase 1 study in the United States for
the treatment of patients with severe SCD. In addition, bluebird is
conducting a long-term safety and efficacy follow-up study
(LTF-303) for subjects with hemoglobinopathies (TDT or severe SCD)
who have been treated with LentiGlobin in bluebird bio-sponsored
clinical studies.
LentiGlobin was granted Orphan Drug status by the U.S. Food and
Drug Administration (FDA) and the European Medicines Agency (EMA)
for the treatment of β-thalassemia and SCD. The FDA granted
Breakthrough Therapy designation to LentiGlobin for the treatment
of transfusion-dependent patients with β-thalassemia major and
Fast-Track Designation for the treatment of beta-thalassemia major
and for the treatment of certain patients with severe SCD. bluebird
bio is participating in the EMA’s Adaptive Pathways pilot program,
which is part of the EMA’s effort to improve timely access for
patients to new medicines. The EMA granted Priority Medicines
(PRIME) eligibility to LentiGlobin for the treatment of TDT.
About TDTTransfusion-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 Celgene. 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, Washington, Durham, North Carolina and Zug,
Switzerland.
LentiGlobin and Lenti-D are trademarks of bluebird bio, Inc.
Forward-Looking StatementsThis 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 Securities and Exchange Commission. All
information in this press release is as of the date of the release,
and bluebird bio undertakes no duty to update this information
unless required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20180418006407/en/
bluebird bioInvestors:Elizabeth Pingpank,
617-914-8736epingpank@bluebirdbio.comorMedia:Stephanie Fagan,
201-572-9581sfagan@bluebirdbio.com
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