If approved, eli-cel will be the first and only
gene therapy for the treatment of early active CALD, a rare
neurodegenerative disease that primarily affects young children and
leads to irreversible loss of neurologic function and death
PDUFA goal date is set for September 16,
2022
bluebird bio, Inc. (Nasdaq: BLUE) today announced the
outcome of the U.S. Food and Drug Administration’s (FDA) Cellular,
Tissue, and Gene Therapies Advisory Committee (CTGTAC) discussion
of elivaldogene autotemcel (eli-cel) for the treatment of early
active cerebral adrenoleukodystrophy (CALD) in patients less than
18 years of age who do not have an available and willing human
leukocyte antigen (HLA)-matched sibling hematopoietic stem cell
(HSC) donor.
On the question “Do the benefits of eli-cel outweigh the risks,
for the treatment of any sub-population of children with early
active cerebral adrenoleukodystrophy (CALD)?” the CTGTAC voted 15
(yes) to 0 (no).
“For decades, the CALD community has fought for the opportunity
to stave off the rapid, irreversible decline associated with this
devastating disease,” said Andrew Obenshain, chief executive
officer, bluebird bio. “Today we are one step closer to delivering
a potentially lifesaving therapy for CALD. We are grateful to the
families, clinicians and committee members who participated in
today’s advisory committee discussion and remain committed to
working with the FDA as it completes its review of the eli-cel
Biologics License Application.”
CALD is a rare, progressive, neurodegenerative disease that
primarily affects young boys and causes behavioral, cognitive, and
neurological deficits. Nearly half of patients who do not receive
treatment die within five years of symptom onset. Allogeneic
hematopoietic stem cell transplant (allo-HSCT) is currently the
only effective treatment option but is associated with serious
potential complications and mortality that increase in patients
without a matched sibling donor. If approved, eli-cel will be the
first approved gene therapy to address the underlying genetic cause
of disease for patients living with CALD in the U.S. – offering the
more than 70% of patients diagnosed with CALD who do not have a
matched sibling donor an alternative to allo-HSCT.
The committee’s recommendation is based on the Biologics License
Application (BLA) currently under priority review by the FDA with a
PDUFA goal date set for September 16, 2022. The BLA for eli-cel is
supported by efficacy and safety data from the completed Phase 2/3
Starbeam study (ALD-102) (N=32). Additionally, the BLA contains
data for 35 subjects dosed in the Phase 3 ALD-104 study. In
clinical studies, patients treated with eli-cel were more likely to
achieve both overall and event-free survival than allo-HSCT
patients without a matched sibling donor, with the clearest benefit
for patients without a matched donor of any type.
The eli-cel clinical program was placed on a clinical hold
following a Suspected Unexpected Serious Adverse Reaction (SUSAR)
of myelodysplastic syndrome (MDS) in August 2021. Consistent with
this known risk, two additional cases of MDS have subsequently been
reported. All patients who received eli-cel in the clinical program
continue to be closely monitored, per study protocols.
The CTGTAC also discussed the overall safety of lentiviral
vector (LVV) gene therapies, concluding in a 13 to 1 vote that the
safety data from lovo-cel for sickle cell disease is not relevant
to the review of eli-cel. In addition to granting eli-cel BLA
priority review, the FDA previously granted eli-cel Orphan Drug
status, Rare Pediatric Disease designation, and Breakthrough
Therapy designation. bluebird bio is eligible to receive a priority
review voucher upon potential approval of eli-cel.
Tomorrow, June 10, 2022, the CTGTAC will convene to discuss the
efficacy and safety of betibeglogene autotemcel (beti-cel), an
investigational LVV gene therapy for patients with beta-thalassemia
who require regular red blood cell transfusions.
About CALD
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic
disorder that primarily affects males; worldwide, an estimated one
in 21,000 male newborns are diagnosed with ALD. The disorder is
caused by mutations in the ABCD1 gene that affect the production of
adrenoleukodystrophy protein (ALDP) and subsequently leads to toxic
accumulation of very long-chain fatty acids (VLCFAs), primarily in
the adrenal gland and white matter of the brain and spinal cord.
Approximately 40% of boys with ALD will develop CALD, the most
severe form of ALD. CALD is a progressive and irreversible
neurodegenerative disease that involves the breakdown of myelin,
the protective sheath that nerve cells need to function
effectively, especially for thinking and muscle control. The onset
of symptoms of CALD typically occurs in childhood (median age 7).
Early diagnosis and treatment of CALD is essential, as nearly half
of patients who do not receive treatment die within five years of
symptom onset.
About elivaldogene autotemcel (eli-cel) gene
therapy
eli-cel (pronounced ELL ee cell) uses ex vivo transduction with
the Lenti-D lentiviral vector (LVV) to add functional copies of the
ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs).
The addition of the functional ABCD1 gene allows patients to
produce the ALD protein (ALDP), which is thought to facilitate the
breakdown of very long-chain fatty acids (VLCFAs). The expression
of ALDP and effect of eli-cel is expected to be life-long. The goal
of treatment with eli-cel is to stop the progression of CALD and,
consequently, preserve as much neurological function as possible,
including the preservation of motor function and communication
ability. Importantly, with eli-cel, there is no need for donor HSCs
from another person.
bluebird bio’s clinical development program for eli-cel includes
the completed pivotal Phase 2/3 Starbeam study (ALD-102) and the
ongoing Phase 3 ALD-104 study, which has completed enrollment and
treatment of all patients. Additionally, bluebird bio is conducting
a long-term safety and efficacy follow-up study (LTF-304) for
patients who have received eli-cel for CALD and completed two years
of follow-up in ALD-102 or ALD-104. Enrollment into studies of
eli-cel is currently on hold with the FDA and follow-up of all
patients continues, per protocol.
In ALD-102, 90.6% (29/32) of patients met the primary endpoint
of Major Functional Disabilities (MFD)-free survival at 24 months.
As previously reported, two patients withdrew from study ALD-102 at
investigator discretion, and one additional subject experienced
rapid disease progression early after treatment, resulting in MFDs
and subsequent death. All patients who completed ALD-102 enrolled
in a long-term follow-up study (LTF-304). The median duration of
follow-up is approximately four years (49 months; 13.4, 88.1).
Adverse reactions attributed to eli-cel observed in clinical
trials include myelodysplastic syndrome, viral cystitis,
pancytopenia, and nausea and vomiting. There have been no reports
of graft-versus-host-disease, graft failure or rejection,
transplant-related mortality, or replication competent lentivirus
in the 67 patients who received eli-cel in clinical studies
(ALD-102, ALD-104, LTF-304).
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give
patients and their families more bluebird days.
With a dedicated focus on severe genetic diseases, bluebird has
industry-leading clinical and research programs for sickle cell
disease, beta-thalassemia and cerebral adrenoleukodystrophy and is
advancing research to apply new technologies to these and other
diseases. We custom design each of our therapies to address the
underlying cause of disease and have developed in-depth and
effective analytical methods to understand the safety of our
lentiviral vector technologies and drive the field of gene therapy
forward.
Founded in 2010, bluebird has the largest and deepest ex-vivo
gene therapy data set in the world—setting the standard for
industry. Today, bluebird continues to forge new paths, combining
our real-world experience with a deep commitment to patient
communities and a people-centric culture that attracts and grows a
diverse flock of dedicated birds.
For more information, visit bluebirdbio.com or follow us
on social media at @bluebirdbio, LinkedIn,
Instagram and YouTube.
Lenti-D and bluebird bio are trademarks of bluebird bio,
Inc.
bluebird bio Cautionary Statement Regarding Forward-Looking
Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of
1995. All statements that are not statements of historical facts
are, or may be deemed to be, forward-looking statements. Such
forward-looking statements are based on historical performance and
current expectations and projections about our future goals, plans
and objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future goals, plans and objectives to differ materially from
those expressed in, or implied by, the statements. No
forward-looking statement can be guaranteed. Forward-looking
statements in this press release should be evaluated together with
the many risks and uncertainties that affect bluebird bio’s
business, particularly those identified in the risk factors
discussion in bluebird bio’s Annual Report on Form 10-K, as updated
by our subsequent Quarterly Reports on Form 10-Q, Current Reports
on Form 8-K and other filings with the Securities and Exchange
Commission. 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 will not continue; the risk that
additional insertional oncogenic or other safety events associated
with lentiviral vector, drug product, or myeloablation will be
discovered or reported over time; and the risk that any one or more
of our product candidates, will not be successfully developed,
approved by the FDA or commercialized. The forward-looking
statements included in this document are made only as of the date
of this document and except as otherwise required by applicable
law, bluebird bio undertakes no obligation to publicly update or
revise any forward-looking statement, whether as a result of new
information, future events, changed circumstances or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20220609006060/en/
Investors: Courtney O’Leary, 978-621-7347
coleary@bluebirdbio.com Media: Jess Rowlands, 857-299-6103
jess.rowlands@bluebirdbio.com
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