Up to 3.8 years of transfusion independence in
Phase 1/2 Northstar (HGB-204) study in patients with TDT who do not
have a β0/β0 genotype
Four of five evaluable patients achieved
transfusion independence in ongoing Phase 3 Northstar-2 (HGB-207)
study of patients with TDT who do not have a β0/β0 genotype
In patients who were free from transfusions for
at least three months total hemoglobin levels were 10.2–13.6 g/dL
in the ongoing Phase 3 Northstar-3 (HGB-212) study in patients with
TDT who have a β0/β0 genotype or IVS-I-110 mutation
bluebird bio, Inc. (Nasdaq:BLUE) announced updated results from
the completed Phase 1/2 Northstar (HGB-204) study, and new data
from the Phase 3 Northstar-2 (HGB-207) and Phase 3 Northstar-3
(HGB-212) clinical studies of its LentiGlobin® gene therapy for
patients with transfusion-dependent β-thalassemia (TDT), at the
24th European Hematology Association (EHA) Congress in Amsterdam,
the Netherlands.
“The maturing data from our clinical studies of LentiGlobin for
TDT show that patients across genotypes are able to achieve and
maintain transfusion independence with stable production of gene
therapy-derived-hemoglobin, HbAT87Q, extending for years,” said
David Davidson M.D., chief medical officer, bluebird bio. “In
patients who achieve transfusion independence, we have observed
decreased liver iron concentration over time and improved markers
of erythropoiesis, demonstrating the transformative
disease-modifying potential of gene therapy for patients with
TDT.”
TDT is a severe genetic disease caused by mutations in the
β-globin gene that result in reduced or absent hemoglobin (Hb). In
order to survive, people with TDT maintain Hb levels through
lifelong chronic blood transfusions. These transfusions carry the
risk of progressive multi-organ damage due to unavoidable iron
overload.
LentiGlobin for β-thalassemia addresses the underlying genetic
cause of TDT by adding functional copies of a modified form of the
β-globin gene (βA-T87Q-globin gene) into a patient’s own
hematopoietic (blood) stem cells (HSCs). This means there is no
need for donor HSCs from another person, as is required for
allogeneic HSC transplantation (allo-HSCT). Once a patient has the
βA-T87Q-globin gene, they have the potential to produce HbAT87Q,
which is gene therapy-derived-Hb, at levels that eliminate or
significantly reduce the need for transfusions.
bluebird bio’s clinical development program for LentiGlobin in
TDT includes studies across patient genotypes, including those who
do not have a β0/β0 genotype as well as those with a β0/β0
genotype.
“Patients living with β-thalassemia who have a β0/β0 genotype or
an IVS-I-110 mutation typically have low levels of endogenous
hemoglobin,” said Andreas Kulozik, M.D., Ph.D., Heidelberg
University Hospital, Heidelberg, Germany. “Transfusion independence
is a goal for the treatment of TDT, regardless of genotype. Early
results from the ongoing Phase 3 study in patients with a β0/β0
genotype or an IVS-I-110 mutation show gene
therapy-derived-hemoglobin significantly contributes to improved
total hemoglobin levels.”
Northstar (HGB-204)
The results reported for the completed Phase 1/2 Northstar
(HGB-204) study reflect data as of December 13, 2018; of the 18
patients in the study, 10 patients do not have a
β0/β0 genotype and eight have a β0/β0 genotype. All 18
patients have completed the two-year study and enrolled in the
long-term follow-up study, LTF-303.
Eight of 10 treated patients who do not have a
β0/β0 genotype achieved transfusion independence (TI), meaning
they had not received a transfusion for at least 12 months or more
and maintained a weighted average Hb ≥9 g/dL.
These eight patients had a median weighted average Hb during TI
of 10.3 g/dL (min–max: 9.3–13.2 g/dL) and continued to maintain TI
for up to 45 months. The patient follow-up period is calculated
from infusion of LentiGlobin to the last study visit.
In patients who have a β0/β0 genotype, three of the eight
achieved TI and maintained a median weighted average Hb ranging
from 9.5–10.1 g/dL for a median duration of 16.4 months (min–max:
16.1–20.8 months).
An exploratory assessment was conducted to assess liver iron
concentration (LIC) in the 11 patients from the Northstar study who
achieved TI. Increased iron levels are a consequence of frequent
transfusions. High iron levels can cause organ damage, which many
patients with TDT are at risk of and must manage through chelation
regimens.
LIC was measured at baseline and then every 12 months after
treatment with LentiGlobin. Patients reinitiated iron chelation
therapy at a median of 13 months after LentiGlobin infusion
(min–max: 2–16 months). Over time, LIC began to decrease in all 11
patients with the largest decrease observed in patients who had 48
months of data available (n=4). A median 56 percent reduction
(min–max: 38–83 percent) was reported in these four patients.
Northstar-2 (HGB-207) Efficacy
As of December 13, 2018, 20 patients who do not have β0/β0
genotypes have been treated in the Phase 3 Northstar-2 study.
Patient age ranged from 8–34 years, with five pediatric (<12
years) and 15 adolescent/adult (≥12 years) patients.
Four of five evaluable patients achieved TI and maintained a
median weighted average Hb of 12.4 g/dL (min–max: 11.5–12.6 g/dL).
These four patients continued to maintain TI for a median duration
of 13.6 months (min–max: 12–18.2 months) at the time of the data
cut off.
Thirteen of 14 patients with at least three months of follow-up
were free from transfusions for at least three months. Total Hb
levels in these patients ranged from 8.8–13.3 g/dL at the time of
the last study visit. HbAT87Q levels were stable over time in
patients who were free from transfusions; at Month 6 (n=10) median
HbAT87Q was 9.5 g/dL and at Month 12 (n=7) median HbAT87Q was 9.3
g/dL.
An exploratory analysis was conducted with bone marrow from
seven 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 (RBC)
production, characteristic of patients with TDT. In these seven
patients, all of whom had stopped chronic transfusions, an increase
in the myeloid to erythroid ratio was observed, suggesting
improvement in RBC production.
Northstar-3 (HGB-212) Efficacy
As of April 12, 2019, 11 patients with TDT and a β0/β0 genotype
or an IVS-I-110 mutation had been treated in the Phase 3
Northstar-3 study.
The one patient evaluable for TI achieved and maintained it and
had a total Hb of 13.6 g/dL at the Month 16 follow-up.
Five patients had stopped transfusions for at least three months
and had Hb levels of 10.2–13.6 g/dL at the time of the last study
visit (5 – 16 months post-treatment). Of these patients, all of
those who reached six months of follow-up (n=4) had HbAT87Q levels
of at least 8 g/dL.
LentiGlobin for TDT Safety
Non-serious adverse events (AEs) observed during clinical
studies that were attributed to LentiGlobin for TDT were hot flush,
dyspnoea, abdominal pain, pain in extremities and non-cardiac chest
pain. One serious adverse event (SAE) of thrombocytopenia was
considered possibly related to LentiGlobin for TDT.
Additional AEs observed in clinical studies were consistent with
the known side effects of HSC collection and bone marrow ablation
with busulfan, including SAEs of veno-occlusive disease.
As of the data cut off dates stated above, a total of 49
pediatric, adolescent and adult patients with TDT and a
non-β0/β0 or β0/β0 genotype, including patients with
IVS-I-110 mutations, have been treated with LentiGlobin for
TDT in the Northstar, Northstar-2 and Northstar-3 studies.
About LentiGlobin for β-Thalassemia
The European Commission (EC) granted conditional marketing
authorization for LentiGlobin for TDT, to be marketed as ZYNTEGLO®
(autologous CD34+ cells encoding βA-T87Q-globin gene) gene therapy,
for patients 12 years and older with TDT who do not have a
β0/β0 genotype, for whom hematopoietic stem cell (HSC)
transplantation is appropriate, but a human leukocyte antigen
(HLA)-matched related HSC donor is not available.
ZYNTEGLO adds functional copies of a modified form of the
β-globin gene (βA-T87Q-globin gene) into a patient’s own
hematopoietic (blood) stem cells (HSCs). Once a patient has the
βA-T87Q-globin gene, they have the potential to produce HbAT87Q,
which is gene therapy-derived-hemoglobin, at levels that eliminate
or significantly reduce the need for transfusions. Upon engraftment
and achievement of transfusion independence, effects of ZYNTEGLO
are expected to be lifelong.
The EMA previously granted Priority Medicines (PRIME)
eligibility and Orphan Medicinal Product designation to ZYNTEGLO
for the treatment of TDT. ZYNTEGLO 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.
The U.S. Food and Drug Administration (FDA) also granted
ZYNTEGLO Orphan Drug status and Breakthrough Therapy designation
for the treatment of TDT.
LentiGlobin for TDT continues to be evaluated in the ongoing
Phase 3 Northstar-2 and Northstar-3 studies and the long-term
follow-up study LTF-303. For more information about the ongoing
clinical studies, visit www.northstarclinicalstudies.com or
clinicaltrials.gov and use identifier NCT01745120 for Northstar
(HGB-204), NCT02906202 for Northstar-2 (HGB-207), NCT03207009 for
Northstar-3 (HGB-212) and NCT02633943 for LTF-303.
About bluebird bio, Inc.
bluebird bio is pioneering gene therapy with purpose. From
our Cambridge, Mass., headquarters, we’re developing gene
therapies for severe genetic diseases and cancer, with the goal
that people facing potentially fatal conditions with limited
treatment options can live their lives fully. Beyond our labs,
we’re working to positively disrupt the healthcare system to create
access, transparency and education so that gene therapy can become
available to all those who can benefit.
bluebird bio is a human company powered by human stories. We’re
putting our care and expertise to work across a spectrum of
disorders by researching cerebral adrenoleukodystrophy, sickle cell
disease, transfusion-dependent β-thalassemia and multiple myeloma
using three gene therapy technologies: gene addition, cell therapy
and (megaTAL-enabled) gene editing.
bluebird bio has additional nests in Seattle,
Wash.; Durham, N.C.; and Zug, Switzerland. For more
information, visit bluebirdbio.com.
Follow bluebird bio on social
media: @bluebirdbio, LinkedIn, Instagram and YouTube.
ZYNTEGLO and LentiGlobin are trademarks of bluebird bio.
The full common name for ZYNTEGLO: A genetically modified
autologous CD34+ cell enriched population that contains
hematopoietic stem cells transduced with lentiviral vector encoding
the βA-T87Q-globin gene.
Forward-Looking Statements
This release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995.
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 efficacy and safety
results from our prior and ongoing clinical trials of LentiGlobin
for TDT will not continue or be repeated in our ongoing or planned
clinical trials of LentiGlobin for TDT; the risk that the current
or planned clinical trials of LentiGlobin for TDT will be
insufficient to support future regulatory submissions in the U.S.
and EU or additional marketing authorizations; the risk that the
production of HbAT87Q may not be sustained over extended periods of
time; and the risk that we may not secure adequate pricing or
reimbursement to support continued development or commercialization
of LentiGlobin for TDT. 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 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/20190614005119/en/
bluebird bioInvestors:Elizabeth Pingpank,
617-914-8736epingpank@bluebirdbio.comorMedia:Catherine Falcetti,
339-499-9436cfalcetti@bluebirdbio.com
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