90% of evaluable patients (27/30) alive and
free of major functional disabilities (MFDs) at two years follow-up
in Phase 2/3 Starbeam study (ALD-102)
Patients in long-term follow-up study (LTF-304)
continue to remain alive and MFD-free through up to nearly seven
years of follow-up, suggesting eli-cel stabilizes the progression
of disease
No reports of graft failure, graft rejection,
graft-versus-host disease, replication competent lentivirus or
insertional oncogenesis in the 51 patients treated with eli-cel in
clinical studies (ALD-102/LTF-304 and ALD-104)
Data presented in oral session during
Presidential Symposium at the 47th Annual Meeting of the EBMT
bluebird bio, Inc. (Nasdaq: BLUE) announced new data from the
clinical development program for its investigational elivaldogene
autotemcel (eli-cel, Lenti-D™) gene therapy in patients with
cerebral adrenoleukodystrophy (CALD), including updated results
from the pivotal Phase 2/3 Starbeam study (ALD-102) and the
long-term follow-up study LTF-304, as well as safety outcomes from
the Phase 3 ALD-104 study. Data were presented today in an oral
presentation during the Presidential Symposium at the 47th Annual
Meeting of the European Society for Blood and Marrow
Transplantation (EBMT 2021), taking place virtually from March 14 -
17, 2021.
“The progression of CALD may occur rapidly, leading to severe
neurological decline, and often death, of boys with this disease if
untreated. The results presented today show that at 24 months of
follow-up, 90% of patients (27/30) in our pivotal study of eli-cel
(ALD-102) were alive and free of major functional disabilities
(MFDs). As we continue the long-term follow-up of these patients,
we are encouraged that there are now 14 boys who have reached at
least their Year 5 follow-up visit and continue to be living
without MFDs, demonstrating the potential for a prolonged treatment
effect,” said Richard Colvin, M.D., Ph.D., VP, head of severe
genetic diseases clinical research and development, bluebird bio.
“There is a great need for alternative treatment options that
reduce the risk of the serious immune complications associated with
allogeneic stem cell transplantation, the current standard of care
for CALD. Today’s presentation continues to illustrate the
potential of eli-cel as a one-time, durable treatment option for
this devastating disease.”
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic
disorder that is estimated to affect one in 21,000 male newborns
worldwide. ALD is caused by mutations in the ABCD1 gene that affect
the production of adrenoleukodystrophy protein (ALDP) and
subsequently cause toxic accumulation of very long-chain fatty
acids (VLCFAs) primarily in the adrenal cortex and white matter of
the brain and spinal cord.
Approximately 40% of boys with adrenoleukodystrophy will develop
CALD, the most severe form of ALD, which is progressive and
neurodegenerative, involving the breakdown of the nerve cells in
the brain that are responsible for thinking and muscle control.
CALD is associated with six MFDs, which severely compromise a
patient’s ability to function independently: loss of communication,
cortical blindness, need for tube feeding, total incontinence,
wheelchair dependence, and complete loss of voluntary movement.
CALD usually occurs in early childhood and progresses rapidly, if
untreated, leading to severe loss of neurologic function, and
eventual death, in most patients.
Eli-cel is a one-time investigational gene therapy designed to
add functional copies of the ABCD1 gene into a patient’s own
hematopoietic (blood) stem cells (HSCs) that have been transduced
ex vivo with the Lenti-D lentiviral vector (LVV). The addition of
the functional ABCD1 gene allows patients to produce the
adrenoleukodystrophy protein (ALDP), which is thought to activate
the breakdown of VLCFAs. The goal of treatment with eli-cel is to
stabilize the progression of CALD and consequently preserve as much
neurological function as possible. Importantly, with eli-cel, there
is no need for donor HSCs from another person.
“CALD is a terrible disease that occurs in early childhood and,
if left untreated, often leads to eventual death for these boys, a
difficult fact for any clinician to bear. These data from the Phase
2/3 Starbeam study show some potentially promising evidence, with
up to almost seven years of follow-up and nearly all patients have
a stable neurologic function score (n=31/32), indicating that
minimal neurologic function was lost following eli-cel infusion. In
addition there were no reports of graft failure, graft rejection,
or graft-versus-host disease,” said Dr. J�rn-Sven Kühl, Department
of Pediatric Oncology, Hematology and Hemostaseology, Center for
Women’s and Children’s Medicine, University Hospital Leipzig.
“These long-term results therefore suggest treatment with eli-cel
may stabilize disease progression and consequently preserve as much
neurological function as possible in boys with CALD.”
Starbeam Study (ALD-102)/Long-Term
Follow-Up Study (LTF-304)
The ALD-102 study has completed enrollment. All reported data
below from ALD-102 are as of October 2020 and all reported data
below from LTF-304 are as of November 2020. These data reflect a
total population of 32 patients with a median follow-up time of
38.6 months (13.4 – 82.7 months).
Of the 32 patients who have received eli-cel in ALD-102, 27 have
completed the study and enrolled in a long-term follow-up study
(LTF-304). Two additional patients continue to be followed in
ALD-102 and have not reached 24 months post-treatment. As
previously reported, two patients withdrew from the study at
investigator discretion, and one experienced rapid disease
progression early on-study resulting in MFDs and subsequent death.
To date, 124 patient-years of follow-up have been collected for
ALD-102 and LTF-304.
The primary efficacy endpoint in the study is the proportion of
patients who are alive and free of MFDs at Month 24. Of those
patients who have reached Month 24, 90% (n=27/30) have met the
primary endpoint and continue to be alive and MFD-free at two years
of follow-up. There is no evidence of MFDs through nearly seven
years (up to 82.7 months) of follow-up in the 27 patients who
completed ALD-102. Fourteen patients in LTF-304 have reached at
least their Year 5 follow-up visit, including seven patients who
have reached at least their Year 6 follow-up visit. The two
patients from ALD-102 that have not reached Month 24 have also
shown no evidence of MFDs.
Data on several secondary and exploratory efficacy outcomes are
reported, including changes in neurologic function score (NFS), a
25-point score used to evaluate the severity of gross neurologic
dysfunction across 15 symptoms in six categories; resolution of
gadolinium enhancement (GdE), an indicator of active inflammation
in the brain; and change in Loes score, an MRI measurement of white
matter changes in CALD. Stable NFS at last assessment is defined as
maintaining an NFS <4 without an
increase of >3 points from baseline. Of the 32 patients treated,
31 had stable NFS at last available visit following treatment with
eli-cel, and 23 patients maintained an NFS of 0. An NFS of 0
indicates that there is no observed impairment in the neurologic
functions that are assessed on the 25-point scale. As of available
last visit, 26 of 32 patients had stable Loes scores (≤9 or change
from baseline ≤6) and 28 of 32 were GdE-negative.
The primary safety endpoint is the proportion of patients who
experience acute (≥Grade 2) or chronic graft-versus-host disease
(GvHD) by Month 24. GvHD is a condition that may occur after an
allogeneic hematopoietic stem cell transplant (allo-HSCT), where
the donated cells view the recipient’s body as foreign and attack
the body. No events of acute or chronic GvHD have been reported
post-eli-cel treatment. There have been no reports of graft failure
or graft rejection. In addition, there have been no cases of
replication competent lentivirus or insertional oncogenesis to
date.
The treatment regimen, comprising mobilization/apheresis,
conditioning, and eli-cel infusion, had a safety and tolerability
profile primarily reflective of the known effects of
mobilization/apheresis and conditioning. In ALD-102, as previously
reported, three adverse events (AEs) were considered possibly
related to drug product and include one serious AE (SAE), BK viral
cystitis (n=1, SAE), and two non-serious AEs, vomiting (n=2). All
three AEs resolved with standard measures.
ALD-104 Study
ALD-104 is a Phase 3 study assessing the efficacy and safety of
eli-cel in patients with CALD after myeloablative conditioning
using busulfan and fludarabine, a different chemotherapy
conditioning regimen than what is used in ALD-102 (busulfan and
cyclophosphamide). The primary efficacy endpoint is the proportion
of patients who are alive and free of MFDs at Month 24, and the
primary safety endpoint is the proportion of patients with
neutrophil engraftment after eli-cel infusion. All reported data
below are as of October 2020.
In ALD-104, the 19 patients currently treated with eli-cel have
a median follow-up of 8.6 months (min-max: 0.1 – 16.8 months) to
date. Due to the limited duration of follow-up, only safety data
are being presented. Efficacy data will be presented in a future
scientific forum when sufficient follow-up is reached.
Seventeen of 19 evaluable patients achieved neutrophil
engraftment (NE; pending in two patients as of data cut date) and
15 of 19 evaluable patients had platelet engraftment (PE; pending
in two patients who are awaiting neutrophil engraftment and in two
additional patients as of data cut date). All patients with pending
neutrophil or platelet engraftment had 35 or fewer days of
follow-up.
No events of acute or chronic GvHD have been reported and there
have been no reports of graft failure, graft rejection, cases of
insertional oncogenesis, or replication competent lentivirus.
The treatment regimen, comprising mobilization/apheresis,
conditioning, and eli-cel infusion had a safety and tolerability
profile primarily reflective of the known effects of
mobilization/apheresis and conditioning. As previously reported,
two serious AEs of pancytopenia were considered possibly related to
eli-cel. These two ongoing SAEs were diagnosed approximately two
months post-eli-cel infusion and following NE in two patients. Both
patients achieved PE (Day 104 and 108) and as of last visit (~13
months post-eli-cel infusion) were clinically stable.
An additional previously reported SAE of transverse myelitis was
ongoing as of the data cut. The SAE was diagnosed in the presence
of viral infection (adenovirus and rhinovirus/enterovirus
positivity) approximately six months after eli-cel infusion and
assessed as unrelated to eli-cel. As of the data cut, the patient
was partially responsive to steroids and plasmapheresis and was
experiencing incontinence and ambulation issues.
eli-cel Presentation at
EBMT21
Elivaldogene autotemcel (eli-cel; Lenti-D) gene therapy for
cerebral adrenoleukodystrophy: Updated results from the Phase 2/3
study and safety outcomes report from the Phase 3 study
Presenting Author: J�rn-Sven Kühl, M.D., Department of
Pediatric Oncology, Hematology and Hemostaseology, Center for
Women’s and Children’s Medicine, University Hospital Leipzig
Oral Session & Number: GS2-8 Presidential Symposium
Date & Time: Monday, March 15, 3:33-3:42 PM
CET/10:33-10:42 AM EDT; Auditorium 1
All EBMT sessions will be available to registered attendees
on-demand on the Annual Meeting website after they are aired
live; content will be accessible online for two months following
the close of the meeting.
About elivaldogene autotemcel (eli-cel, formerly Lenti-D™ gene
therapy)
In October 2020, the European Medicines Agency (EMA) accepted
bluebird bio’s marketing authorization application (MAA) for its
investigational eli-cel gene therapy for the treatment of patients
with cerebral adrenoleukodystrophy (CALD). The EMA accepted eli-cel
gene therapy for the treatment of CALD into its Priorities
Medicines scheme (PRIME) in July 2018, and previously granted
Orphan Medicinal Product designation to eli-cel.
The U.S. Food and Drug Administration (FDA) granted eli-cel
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. in mid-2021.
Eli-cel is not approved for any indication in any geography.
bluebird bio is currently enrolling patients for a Phase 3 study
(ALD-104) designed to assess the efficacy and safety of eli-cel
after myeloablative conditioning using busulfan and fludarabine in
patients with CALD. Contact clinicaltrials@bluebirdbio.com
for more information and a list of study sites.
Additionally, bluebird bio is conducting a long-term safety and
efficacy follow-up study (LTF-304) for patients who have been
treated with eli-cel for CALD and completed two years of follow-up
in bluebird bio-sponsored studies.
The Phase 2/3 Starbeam study (ALD-102) has completed enrollment.
For more information about the ALD-102 study visit:
www.bluebirdbio.com/our-science/clinical-trials or
clinicaltrials.gov and use identifier NCT01896102.
About CALD Early Diagnosis
Early diagnosis of CALD is important, as the outcome of
available treatment varies with the clinical stage of the disease.
Newborn screening for ALD is a critical enabler of early diagnosis
and thus of successful treatment of ALD. Once a patient has been
diagnosed with ALD, regular MRI scans are critical to detect white
matter changes indicative of progression to 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 19 states and the District of Columbia,
accounting for >60 percent of U.S.
newborns. Outside the U.S., the Minister of Health in the
Netherlands has approved the addition of ALD to their newborn
screening program. Even though ALD newborn screening has not been
implemented in most EU countries, efforts to begin pilot programs
are slowly progressing.
More information about newborn screening is available at
https://www.bluebirdbio.com/patients-and-advocacy/newborn-screening-toolkit-for-ALD.
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.
eli-cel, Lenti-D 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 for eli-cel in the U.S. and E.U. 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: risks that the efficacy and safety results
for eli-cel from the Starbeam Study seen to date will not continue
or persist, the risk of cessation or delay of any of the ongoing
clinical studies and/or our development of eli-cel, the risks
regarding future potential regulatory approvals of eli-cel,
including the risk that the Starbeam Study will be insufficient to
support regulatory submissions or marketing approval in the U.S.
and EU, the risk that our submissions for regulatory approvals will
not be submitted or accepted for filing by the regulatory
authorities on the timeframe we expect or at all, the risk that any
one or more of our product candidates will not be successfully
developed, approved or commercialized, the risk that eli-cel is
associated with insertional oncogenesis or other safety events that
impact the risk-benefit profile of the therapy, and the risk that
the clinical holds imposed by the FDA on our clinical studies in
sickle cell disease and beta-thalassemia programs will extend to
the clinical studies of eli-cel. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210315005105/en/
Media: Victoria von Rinteln, 617-914-8774
vvonrinteln@bluebirdbio.com Catherine Falcetti, 617-583-3411
cfalcetti@bluebirdbio.com Investors: Elizabeth Pingpank,
617-914-8736 epingpank@bluebirdbio.com
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