VIENNA & CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and rare diseases and T cell-based immunotherapies, today announced long-term follow up of two patients with beta-thalassemia major and early safety and efficacy data in the first patient with severe sickle cell disease (SCD) treated with LentiGlobin BB305 product candidate in the HGB-205 study. These data were presented today at the 20th Congress of the European Hematology Association (EHA) in Vienna, Austria by Marina Cavazzana, M.D., Ph.D., lead investigator of the HGB-205 study and professor of hematology at Paris Descartes University, head of the department of Biotherapy Hospital, the clinical research INSERM center of Biotherapy at Necker Enfants Malades, (Assistance Publique-Hôpitaux de Paris) and the Lymphohematopoiesis Laboratory, Institute of Genetic Diseases, Imagine, Paris, France.
Key findings:
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Beta-thalassemia:
- As of May 2015, Subjects 1201 and 1202 with beta-thalassemia major remained transfusion-independent for 16 and 14 months, respectively, with persistent stable expression of HbAT87Q. Neither has experienced a LentiGlobin-related adverse event.
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Sickle Cell Disease:
- The proportion of anti-sickling hemoglobin being produced by the first-ever patient with severe SCD treated with gene therapy (Subject 1204) is rising steadily and accounted for 45% of all hemoglobin production (40% HbAT87Q + 5% HbF) at the patient’s six-month visit post-drug product infusion; this is above the 30% threshold expected to potentially achieve a disease-modifying clinical effect.
- As of May 2015, Subject 1204 had been free of transfusions for more than three months without complications or hospitalizations for SCD-related events post-transplant, and with improvement in hemolysis markers.
“These data are promising for patients living with beta-thalassemia major and severe sickle cell disease, two devastating, genetically-based hematologic diseases that have a profound impact on both quality of life and life expectancy,” said Professor Cavazzana. “The steady rise and high-level of HbAT87Q production in our patient with severe sickle cell disease is cause for optimism as we expect levels of anti-sickling hemoglobin of 30 percent or more could significantly improve and potentially eliminate the serious and life-threatening complications associated with sickle cell disease.”
bluebird bio also announced that the first patient with severe SCD has been infused in the HGB-206 U.S.-based clinical study at the National Institutes of Health Clinical Center in Bethesda, Maryland. HGB-206 is a Phase 1 clinical trial evaluating the safety and efficacy of bluebird bio’s LentiGlobin BB305 product candidate in subjects with severe SCD.
“Today’s data further demonstrate the potentially transformative effects of gene therapy for the treatment of beta-hemoglobinopathies and support our global regulatory strategy for LentiGlobin in beta-thalassemia major, with the goal of potentially accelerated approvals in the EU and U.S.,” said David Davidson, M.D., chief medical officer, bluebird bio. “We are excited that the promising early results for LentiGlobin in beta-thalassemia major are now extending to the first treated patient with severe sickle cell disease. With the treatment of the first patient with severe sickle cell disease in the HGB-206 study, we look forward to gaining increasing clarity on the potential clinical benefit of LentiGlobin for patients with severe sickle cell disease.”
HGB-205 Study Data
HGB-205 is an ongoing, open-label,
single-center Phase 1/2 study designed to evaluate the safety and
efficacy of LentiGlobin BB305 product candidate for the treatment of
patients with beta-thalassemia major and severe SCD. As of May
2015, two patients with beta-thalassemia major and one patient with
severe SCD have undergone infusion with LentiGlobin BB305 product
candidate in this study.
- Patients with beta-thalassemia major demonstrated continued transfusion independence: The data presented today are an update on those initially presented at EHA in June 2014 and demonstrate a long-term stable and durable response. As reported at ASH in December 2014, Subjects 1201 and 1202 achieved rapid transfusion independence with near-normal hemoglobin levels. As of May 2015, Subjects 1201 and 1202 remained transfusion independent for 16 and 14 months, respectively.
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Early efficacy data is promising in the first subject with severe
SCD treated with gene therapy: The production of anti-sickling
hemoglobin is consistent with a level expected to potentially achieve
a disease-modifying clinical effect in Subject 1204. At the six-month
visit post-drug product infusion, the proportion of anti-sickling
hemoglobin (HbAT87Q + HbF) accounted for 45% of all
hemoglobin production (40% HbAT87Q + 5% HbF). The patient’s
vector copy number in peripheral blood leukocytes was 2.2.
- Subject 1204 had his last red blood cell (RBC) transfusion at day 88. Since his infusion with LentiGlobin, this patient has had no hospitalizations, and has demonstrated improvements in markers of hemolysis, including normalization of reticulocyte count (from 283.3 x 109/L to 131.7 x 109/L) and lactate dehydrogenase (LDH) (from 626 U/L to 254 U/L).
Beta Thalassemia Major |
Severe Sickle
Cell Disease |
||||||
Patient | 1201 | 1202 | 1204 | ||||
Enrollment age/Sex | 18/F | 16/M | 13/M | ||||
Country of Origin | Syria | France | France | ||||
Genotype | B0/BE | B0/BE | BS/BS | ||||
Transfusion requirements (mls/kg/year) | 139 | 188 | 170 | ||||
CD34+ VCN in drug substance | 1.5 | 2.1 | 1.2/1.0* | ||||
CD34+ cell count (x106/kg) in drug substance | 8.9 | 13.6 | 5.6 | ||||
Days to neutrophil engraftment | Day +13 | Day +15 | Day +37 | ||||
HbAT87Q/total Hb (g/dL) at last visit | 7.3/10.5 | 9.7/12.8 | 4.3/10.6 | ||||
Last study follow up (months)** | 15 | 15 | 6 | ||||
*If more than one drug substance was manufactured for a subject, the VCN of each drug substance lot is quantified and the cell count is combined.
** Last scheduled study visit for which results were available as of May 2015
In the HGB-205 study, treatment with our LentiGlobin BB305 product candidate has been well-tolerated to-date, with no LentiGlobin-related adverse events observed. All of the adverse events observed are consistent with myeloablative conditioning. All three subjects successfully engrafted and insertional site analyses (ISAs) demonstrate highly polyclonal reconstitution without clonal dominance.
Investor Conference Call and Webcast Information
bluebird
bio will host a conference call and webcast on Monday, June 15 at 8:00
a.m. ET to review the data presented at EHA. The event will be webcast
live and can be accessed under "Calendar of Events" in the Investors and
Media section of the company's website at www.bluebirdbio.com.
Alternatively, investors may listen to the call by dialing (844)
825-4408 from locations in the United States and (315) 625-3227 from
outside the United States.
About Beta-thalassemia
Beta-thalassemia is an inherited
blood disease that can cause severe anemia. Patients with
beta-thalassemia cannot make enough of the beta-globin part of
hemoglobin, the protein used by red blood cells to carry oxygen
throughout the body. Approximately 60,000 children are born with a
serious form of the disease every year, making it one of the most common
genetic diseases in the world. In its most severe form, beta-thalassemia
is fatal if not treated.
Treating beta-thalassemia includes frequent and lifelong blood transfusions, which deliver red blood cells to the body to correct the anemia. However, blood transfusions also cause excess iron to build up in the body, which can damage organs and cause additional issues, such as abdominal pain, weakness, fatigue, joint pain, endocrine dysfunction, liver cirrhosis and heart failure. Patients who receive ongoing blood transfusions must also receive treatment to remove the excess iron. The only currently available curative treatment option for beta-thalassemia is allogeneic hematopoietic stem cell transplant. However, these transplants are typically offered to pediatric patients with matched related donors (occurring in less than 25 percent of all cases), due to the significant risk of transplant-related morbidity and mortality.
About Sickle Cell Disease
Sickle cell disease (SCD) is a
hereditary blood disorder resulting from a mutation in the beta-globin
gene that causes polymerization of hemoglobin proteins and abnormal red
blood cell function. The symptoms of SCD include anemia, vaso-occlusive
crises (a painful complication caused by obstruction of the blood
vessels), infections, stroke, and progressive end-organ damage leading
to overall poor quality of life and early death in a large subset of
patients. The global incidence of SCD is estimated to be 300,000 births
annually, and the global prevalence of the disease is estimated to be
about 25 million.
Patients with severe SCD typically receive chronic blood transfusion regimens or hydroxyurea. Chronic transfusions for SCD introduce the risk of iron overload, which over time contributes to mortality through iron-associated heart and liver toxicity, and patients must adhere to daily iron chelation regimens. While hydroxyurea has been shown to significantly reduce the burden of vaso-occlusive crisis and related complications, it does not eliminate them. The only potentially curative therapy is allogeneic hematopoietic stem cell transplant (HSCT). Because of the significant morbidity and mortality risks associated with transplants, they are usually offered only to patients who have sibling matched donors and only 10 percent of SCD patients of African descent are able to find such donors.
About the HGB-205 Study
HGB-205 is an ongoing, open-label
Phase 1/2 study designed to evaluate the safety and efficacy of bluebird
bio’s LentiGlobin BB305 product candidate in the treatment of subjects
with beta-thalassemia major and severe sickle cell disease (SCD). The
study is designed to enroll up to seven subjects who will be followed to
evaluate safety and transfusion requirements post-transplant. Among
patients with SCD 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 the HGB-206 Study
HGB-206 is an ongoing, open-label
Phase 1 study designed to evaluate the safety and efficacy of
LentiGlobin BB305 product candidate in the treatment of subjects with
severe sickle cell disease (SCD). The study is designed to enroll up to
eight subjects to evaluate safety and efficacy as measured by changes in
red cell function tests and hemolysis markers, as well as clinical
events secondary to SCD, including vaso-occlusive crises or acute chest
syndrome events. For information on the HGB-206 study, please visit
clinicaltrials.gov using the identifier NCT02140554.
About bluebird bio, Inc.
With its lentiviral-based gene
therapy and gene editing capabilities, bluebird bio has built an
integrated product platform with broad potential application to severe
genetic diseases and T cell-based immunotherapy. bluebird bio’s clinical
programs include Lenti-D™, currently in a Phase 2/3 study, called the
Starbeam Study, for the treatment of childhood cerebral
adrenoleukodystrophy, and LentiGlobin®, currently in three
clinical studies: a global Phase 1/2 study, called the Northstar Study,
for the treatment of beta-thalassemia major; a single-center Phase 1/2
study in France (HGB-205) for the treatment of beta-thalassemia major or
severe sickle cell disease; and a separate U.S. Phase 1 study for the
treatment of sickle cell disease (HGB-206). bluebird bio also has
ongoing preclinical CAR T immuno-oncology programs, as well as discovery
research programs utilizing megaTALs/homing endonuclease gene editing
technologies.
bluebird bio has operations in Cambridge, Massachusetts, Seattle, Washington, and Paris, France. For more information, please visit www.bluebirdbio.com.
About the Institute of Genetic Diseases -- Imagine
Imagine is
a research and innovative healthcare institute of a new type, bringing
together researchers, doctors and patients, with a common goal: to cure
genetic diseases. This new Institute is housed in a 19,000 m2
building located on the campus of the Necker Enfants Malades Hospital,
and brings together over 850 researchers, doctors and healthcare
personnel, with an innovative vision: gathering all those concerned in
the treatment of genetic diseases to create synergy that encourages
transfer of knowledge, to speed up the discovery of new treatments and
diagnoses to meet the expectations of the patients and their families.
About the AP-HP
AP-HP, Greater Paris University Hospital, is
a care provider known worldwide with its 38 hospitals and the largest
university medical center in France and in Europe. Each year, AP-HP
welcomes 7 million patients, takes care of more than 1.1 million
emergencies and makes more than 5 million outpatient visits. AP-HP is
the largest employer in Paris Region with 95,000 people -- doctors,
researchers, paramedical, administrative staff and workers.
Forward-Looking Statements
This release contains
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements regarding
the potential efficacy and safety of the Company’s LentiGlobin product
candidate, in subjects with beta thalassemia major and severe sickle
cell disease, including statements concerning the reduced or eliminated
need for transfusion support for the study subjects and the potential
reduction in symptoms of severe sickle cell disease, statements
concerning the Company’s future plans with respect to LentiGlobin and
its other product candidates and statements concerning the HGB-206
clinical trial in severe sickle cell disease. It should be noted that
the data for LentiGlobin announced from the HGB-205 study at the EHA
Congress are preliminary in nature and the Northstar, HGB-205 and
HGB-206 studies LentiGlobin are not completed. There is limited data
concerning long-term safety and efficacy following treatment with
LentiGlobin drug product. These data may not continue for these subjects
or be repeated or observed in ongoing or future studies involving our
LentiGlobin product candidate, including the HGB-205 Study, the
Northstar Study or the HGB-206 study in severe sickle cell disease. It
is possible that subjects for whom transfusion support has been reduced
or eliminated may receive transfusion support in the future and that the
subject with severe sickle cell disease may experience serious symptoms
of the 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 risk that the preliminary results from our
clinical trials will not continue or be repeated in our ongoing clinical
trials, the risk that previously conducted studies involving similar
product candidates will not be repeated or observed in ongoing or future
studies involving current product candidates, the risk of cessation or
delay of any of the ongoing or planned clinical studies and/or our
development of our product candidates, the risk of a delay in the
enrollment of patients in the Company’s clinical studies, the risk that
our collaboration with Celgene will not continue or will not be
successful, and the risk that any one or more of our product candidates
will not be successfully developed and 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 quarterly report on Form 10-Q, 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.