SKYSONA is the first and only gene therapy
approved in the EU to treat early CALD
CALD is a rare neurodegenerative disease that
can lead to progressive, irreversible loss of neurologic function,
and death
One-time treatment with SKYSONA has been shown
to have a durable effect in improving survival outcomes and
preserving neurologic function across pivotal and long-term
studies, with the longest follow-up of nearly seven years (82.7
months)
SKYSONA uses the patient’s own blood stem cells
and there have been no reports of graft-versus-host disease (GVHD),
graft failure or rejection, or transplant-related mortality (TRM)
(n=51) across clinical studies to-date
bluebird bio, Inc. (Nasdaq: BLUE) today announced that the
European Commission (EC) has granted marketing authorization of
SKYSONA™ (elivaldogene autotemcel, Lenti-D™), a one-time gene
therapy for the treatment of early cerebral adrenoleukodystrophy
(CALD) in patients less than 18 years of age with an ABCD1 genetic
mutation, and for whom a human leukocyte antigen (HLA)-matched
sibling hematopoietic (blood) stem cell (HSC) donor is not
available. SKYSONA is the first one-time gene therapy approved in
the European Union (EU) to treat CALD, a rare neurodegenerative
disease that occurs in childhood and can rapidly lead to
progressive, irreversible loss of neurologic function, and
death.
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 causes 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).1
Early diagnosis of CALD is essential as the outcome of treatment
varies with the clinical stage of the disease. Therefore, treatment
must be administered before the disease progresses too far.
“SKYSONA is the first and only one-time gene therapy approved in
the EU for patients with CALD, a devastating neurodegenerative
disease, and we are immensely grateful to all who have brought us
to this milestone, from the patients and their loved ones, to all
study investigators, regulators, the ALD community and of course,
the extended bluebird family,” said Andrew Obenshain, president,
severe genetic diseases, bluebird bio. “bluebird bio was founded
with the mission of developing a therapy to recode CALD on the
genetic level, and today’s announcement represents over twenty
years of research and development that has laid the groundwork for
future gene therapies to be possible.”
SKYSONA is a one-time gene therapy custom-designed to treat the
underlying cause of the neurologic condition CALD. SKYSONA uses ex
vivo transduction with the Lenti-D lentiviral vector (LVV) to add
functional copies of the ABCD1 gene into a patient’s own HSCs. The
addition of the functional ABCD1 gene allows patients to produce
the ALD protein (ALDP), which is thought to facilitate the
breakdown of VLCFAs. The expression of ALDP and effect of SKYSONA
is expected to be life-long. The goal of treatment with SKYSONA 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
SKYSONA, there is no need for donor HSCs from another person.
Previously, the only therapeutic option available to CALD
patients was transplantation of stem cells from a donor, called
allogeneic hematopoietic stem cell transplant (allo-HSCT), which is
associated with severe potential complications and mortality that
increase in patients without a matched sibling donor (MSD). It is
estimated that more than 80% of patients diagnosed with CALD do not
have an MSD.
SKYSONA was reviewed as part of the European Medicines Agency’s
Priority Medicines scheme (PRIME) and was previously granted Orphan
Medicinal Product status. The marketing authorization is valid in
all 27 member states of the EU, as well as Norway, Liechtenstein,
and Iceland.
Data Supporting Clinical Profile of SKYSONA From Clinical
Development Program ALD-102 and ALD-104 The marketing
authorization of SKYSONA is supported by efficacy and safety data
from the Phase 2/3 Starbeam study (ALD-102). Additionally, the
Phase 3 ALD-104 study (N=19; as of October 2020) is ongoing. All
patients who completed ALD-102, as well as those who will complete
ALD-104, will be asked to participate in a long-term follow-up
study (LTF-304).
The primary efficacy endpoint of the pivotal ALD-102 study was
Major Functional Disabilities (MFD)-free survival, measuring the
proportion of patients who did not have any of the six MFDs, were
alive, did not receive a second allo-HSCT or rescue cell
administration, and had not withdrawn or been lost to follow-up at
Month 24. In ALD-102, 32 patients have been treated with SKYSONA
and, as of October 2020, 30 of 32 patients were evaluable for
follow-up at Month 24. As of the data cutoff date, 90% (27/30) of
the patients met the Month 24 MFD-free survival endpoint. As
previously reported, two patients withdrew from the study at
investigator discretion, and one experienced rapid disease
progression early in the study, resulting in MFDs and subsequent
death.
In ALD-102, 26 of 28 evaluable patients maintained a neurologic
function score (NFS) less than or equal to 1 through Month 24, and
24 of those patients had no change in their NFS, which showed
maintenance of neurological function in the majority of patients.
All patients who completed ALD-102 enrolled for long-term follow-up
in the LTF-304 study.
SKYSONA showed a durable effect on MFD-free survival, with most
patients (26/27, 96.3%) that enrolled in LTF-304 remaining alive
and maintaining their MFD-free status through their last follow-up
on study. The median duration of follow-up was 3.2 years (38.6
months; min.: 13.4; max.: 82.7) and 14 patients reached at least
their Year 5 follow-up visit. One patient enrolled in LTF-304 but
refused further follow-up later.
The treatment regimen, comprising stem cell mobilization and
collection, conditioning, and SKYSONA infusion, had a
safety/tolerability profile primarily reflective of the known
effects of mobilization/apheresis and conditioning.
Adverse reactions attributed to SKYSONA observed in clinical
trials include cystitis viral, pancytopenia, and vomiting.
There have been no reports of graft-versus-host-disease (GVHD),
graft failure or rejection, transplant-related mortality (TRM), or
replication competent lentivirus in the 51 patients treated with
SKYSONA in clinical studies (ALD-102/LTF-304 and ALD-104). Clonal
expansion resulting in clonal predominance has been detected in
some patients treated with SKYSONA. While there have been no
reports of lentiviral vector-mediated oncogenesis, including
myelodysplasia, leukemia, or lymphoma, associated with SKYSONA,
there is a potential risk of malignancy after treatment with
SKYSONA.
For further details, please see the Summary of Product
Characteristics (SmPC).
ALD-103 The efficacy and safety of allo-HSCT in patients
with CALD was observed in a contemporaneous comparator study
ALD-103 (N=59), which assessed safety and efficacy outcomes of this
therapeutic option in boys 17 years of age or younger with CALD. Of
the 59 patients, 27 patients matched the ALD-102 population based
on disease characteristics. This population was further divided
into those who received an allo-HSCT from an MSD (N=10; ALD-103
Efficacy Population with MSD) and those who received an allo-HSCT
from an alternative donor source, i.e., not an MSD (N=17; ALD-103
Efficacy Population without MSD). Proportion of MFD-free survival
at Month 24 was analyzed in ALD-102 (90% [95% CI: 73.5, 97.9];
27/30 evaluable patients) and compared to 17 patients treated with
allo-HSCT without an MSD in ALD-103 (66.7% [95% CI: 29.9, 92.5];
6/9 evaluable patients).
The proportion of evaluable patients who experienced either
acute (≥ Grade II) or chronic GVHD in ALD-102 vs. ALD-103 by Month
24, was 0 vs. 52%. No patients experienced TRM, a secondary
endpoint, at 100 days or 365 days after transplant in ALD-102 and
ALD-104. In contrast, 2/59 (3.4%) patients experienced TRM at 100
days and 8/59 (13.6%) patients experienced TRM at 365 days after
transplant in the ALD-103 Safety Population.
About SKYSONA (elivaldogene autotemcel, formerly Lenti-D™ gene
therapy) The U.S. Food and Drug Administration (FDA) granted
SKYSONA Orphan Drug status, Rare Pediatric Disease designation and
Breakthrough Therapy designation for the treatment of CALD.
bluebird bio is currently on track to submit the Biologics License
Application (BLA) in the U.S. by mid-2021.
In the EU, SKYSONA is approved for the treatment of early CALD
in patients less than 18 years of age with an ABCD1 genetic
mutation, and for whom an HLA-matched sibling HSC donor is not
available. A marketing authorization application for SKYSONA is
currently under review by the Medicines and Healthcare products
Regulatory Agency (MHRA) in Great Britain.
The Phase 3 ALD-104 study, designed to assess the efficacy and
safety of SKYSONA after myeloablative conditioning using busulfan
and fludarabine in patients with CALD, is approaching enrollment
completion; enrollment in Europe is closed.
The Phase 2/3 Starbeam study (ALD-102) is complete. For more
information about our studies, visit:
www.bluebirdbio.com/our-science/clinical-trials or
clinicaltrials.gov.
Additionally, bluebird bio is conducting a long-term safety and
efficacy follow-up study (LTF-304) for patients who have been
treated with SKYSONA for CALD and completed two years of follow-up
in bluebird bio-sponsored studies. Patients treated with SKYSONA in
Europe are expected to enroll in the REG-502 Stargazer
registry.
About CALD Early Diagnosis Early diagnosis of CALD is essential,
as the outcome of treatment varies with the clinical stage of the
disease. Therefore, treatment must be administered before the
disease progresses too far. Newborn screening is a critical enabler
of early diagnosis for ALD and provides access to a window for the
timely commencement of available therapies. Once a patient has been
diagnosed with ALD, regular MRI scans are critical to detect white
matter changes indicative of progression to CALD as, currently,
there is no way to predict who with ALD will develop CALD. In the
absence of newborn screening for ALD, early detection of ALD
symptoms is crucial to allow for timely treatment.
Unfortunately, in most EU countries, there is no newborn
screening for ALD, and therefore it is difficult to detect patients
at risk of developing CALD.
In the U.S., newborn screening for ALD was added to the
Recommended Universal Screening Panel in February 2016 and is
currently active in 20 states and the District of Columbia,
accounting for >60% of U.S.
newborns.
About bluebird bio, Inc. bluebird bio is pioneering gene
therapy with purpose. From our Cambridge, Mass., headquarters,
we’re developing gene and cell 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: cerebral adrenoleukodystrophy, sickle cell disease,
β-thalassemia, and multiple myeloma, using gene and cell therapy
technologies including gene addition, 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.
SKYSONA and bluebird bio are trademarks of bluebird bio,
Inc.
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 company’s expectations and plans for regulatory
submissions and approvals for eli-cel in the United States. 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 Starbeam Study will be
insufficient to support regulatory submissions or marketing
approval in the U.S., or that the FDA may require additional data
or information beyond our current expectations, the risk that our
submissions for regulatory approval in the U.S. will not be
submitted or accepted for filing by the FDA on the timeframe we
expect or at all; and the risk that eli-cel is associated with
insertional oncogenesis or other safety events that impact the
risk-benefit profile of the therapy; the risk that our
commercialization of SKYSONA in the European Union will not be
successful; and the risk that we are not able to negotiate a price
or obtain reimbursement for eli-cel or our other products
sufficient to support commercialization in Europe or the United
States. 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.
1 Mallack et al. MRI
surveillance of boys with X-linked adrenoleukodystrophy identified
by newborn screening: Meta-analysis and consensus guidelines. J
Inherit Metab Disease 2021. 44(3):728-39.
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version on businesswire.com: https://www.businesswire.com/news/home/20210721005331/en/
Media: Victoria von Rinteln, 617-914-8774
vvonrinteln@bluebirdbio.com
Investors: Elizabeth Pingpank, 617-914-8736
epingpank@bluebirdbio.com
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