First in-human pediatric Phase 1/2 study to
evaluate the safety and tolerability of first-in-class gene therapy
targeting infants age ≥3 months and ≤12 months, diagnosed with
nMPS-II
University of Manchester (U.K.) expects to
initiate clinical trial later this year
U.S. Food and Drug Administration (FDA)
previously granted rare pediatric disease and orphan drug
designations for AVR-RD-05, AVROBIO’s investigational gene therapy
for nMPS-II or Hunter syndrome
AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene
therapy company working to free people from a lifetime of genetic
disease, today announced that the U.K. Medicines and Healthcare
Products Regulatory Agency (MHRA), Research Ethics Committee (REC)
and Health Research Authority (HRA) have approved the clinical
trial application (CTA) submitted by AVROBIO’s collaborators at the
University of Manchester, U.K. (UoM) for initiation of the Phase
1/2 clinical trial of investigational autologous hematopoietic stem
cell (HSC) gene therapy in infants diagnosed with neuronopathic
mucopolysaccharidosis type II (nMPS-II) or Hunter syndrome. This
rare and seriously debilitating lysosomal disorder primarily
affects young males.
UoM’s 24-month, non-randomized, open label study will enroll up
to five children aged ≥3 months and ≤12 months diagnosed with
nMPS-II to evaluate the safety and tolerability, pharmacodynamic
and clinical efficacy of HSC gene therapy. The gene therapy, which
AVROBIO refers to as AVR-RD-05, is designed to transduce autologous
(a patient’s own) HSCs ex vivo with a lentiviral vector encoding a
brain-targeted iduronate-2-sulfatase (IDS) enzyme, which is
deficient in these patients.
“We are thrilled to collaborate with the team at UoM to bring to
infants and families living with Hunter syndrome a potential
one-time therapy for this devastating disease. Hunter syndrome
causes complications throughout the body, including severe
neurological, cardiac and respiratory dysfunction, skeletal
malformations and hearing impairment," said Geoff MacKay, president
and CEO of AVROBIO. “This investigational HSC gene therapy which
includes CNS-targeted gene expression has been designed to express
supra-physiological levels of the IDS enzyme in transduced HSCs,
with the intent to correct both the systemic and neurological
manifestations of this disease.”
UoM expects to dose the first patient in the trial in 1H 2023.
The study will be overseen by Robert Wynn, M.D., professor of
Pediatric Hematology at Royal Manchester Children’s Hospital, part
of Manchester University NHS Foundation Trust; Brian Bigger, Ph.D.,
professor of Cell and Gene Therapy at The University of Manchester;
and Simon Jones, M.D., professor of Pediatric Inherited Metabolic
Diseases at the Manchester Centre for Genomic Medicine at Saint
Mary’s Hospital, part of Manchester University NHS Foundation
Trust.
“It’s incredibly exciting to have the opportunity to test our
investigational brain-targeted HSC gene therapy in boys with Hunter
disease,” said Professor Bigger. “There are currently no available
treatments that target the brain in this devastating disorder, so
the approach of tagging the IDS enzyme with a blood-brain-barrier
crossing peptide will enable us to see if this approach can improve
outcomes for patients.”
Professor Bigger has previously published preclinical data
demonstrating that HSC gene therapy deploying a proprietary
blood-brain-barrier crossing ApoEII tag fused to the human IDS
gene, drives expression of IDS-ApoEII in blood cells, enabling both
blood cells that naturally traffic into the brain in traditional
HSC gene therapy and peripheral brain targeted IDS-ApoEII enzyme to
both cross the blood-brain barrier, thus potentially addressing
peripheral disease and normalizing brain pathology. In these mouse
models of Hunter syndrome, brain-targeted HSC gene therapy showed
improvement across multiple metrics, including normalization of
skeletal features such as the cheekbone dimensions, the width of
the humerus and femur bones, correction of neurons in the brain and
the preservation of higher brain functions including working
memory.
To find out more about the trial, contact
mpsiitrial@manchester.ac.uk, Simon.Jones@mft.nhs.uk or
Robert.wynn@mft.nhs.uk.
Previously, the U.S. Food and Drug Administration (FDA) granted
rare pediatric disease and orphan drug designations for
AVR-RD-05.
About Hunter syndrome
Hunter syndrome is caused by a deficiency in the lysosomal
enzyme iduronate-2-sulfatase (IDS), which is essential for breaking
down large sugar molecules. It affects an estimated one in 100,000
to one in 170,000 males worldwide. Children with severe cases of
Hunter syndrome typically show early symptoms of the disease in
infancy and childhood and begin to regress developmentally, losing
basic motor skills and cognitive function over a few years. The
neuronopathic form of MPSII is characterized by cognitive, language
and motor skills declining early in childhood.
The current standard of care is weekly enzyme replacement
therapy (ERT), which can delay some peripheral disease
complications but does not halt overall progression of the disease
and has not been demonstrated to address the central nervous system
(CNS) issues. Even with ERT, people with Hunter syndrome face
life-limiting symptoms and a significantly reduced lifespan.
About AVROBIO
Our vision is to bring personalized gene therapy to the world.
We target the root cause of genetic disease by introducing a
functional copy of the affected gene into patients’ own
hematopoietic stem cells (HSCs), with the goal to durably express
the therapeutic protein throughout the body, including the central
nervous system. Our first-in-class pipeline includes clinical
programs for cystinosis and Gaucher disease type 1, as well as
preclinical programs for Gaucher disease type 3, Hunter syndrome
and Pompe disease. Our proprietary plato® gene therapy platform is
designed to be scaled to support late-stage clinical development
and commercialization globally. We are headquartered in Cambridge,
Mass. For additional information, visit avrobio.com, and follow us
on Twitter and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements,
including statements made pursuant to the safe harbor provisions of
the Private Securities Litigation Reform Act of 1995. These
statements may be identified by words and phrases such as “aims,”
“anticipates,” “believes,” “could,” “designed to,” “estimates,”
“expects,” “forecasts,” “goal,” “intends,” “may,” “plans,”
“possible,” “potential,” “seeks,” “will,” and variations of these
words and phrases or similar expressions that are intended to
identify forward-looking statements. These forward-looking
statements include, without limitation, statements regarding our
business strategy for and the potential therapeutic benefits of our
preclinical and clinical product candidates, including AVR-RD-05
for the treatment of nMPSII or Hunter syndrome, the potential
benefits and incentives provided by the FDA’s rare pediatric
disease and orphan drug designations for AVR-RD-05, statements
regarding the expectations or activities of our collaborators
including timing of clinical trial initiation and dosing of
patients, the design, commencement, enrollment and timing of
planned clinical trials, preclinical or clinical trial results,
product approvals and regulatory pathways, our plans and
expectations with respect to interactions with regulatory agencies,
anticipated benefits of our gene therapy platform including
potential impact on our commercialization activities, timing and
likelihood of success, the expected benefits and results of our
implementation of the plato platform in our clinical trials and
gene therapy programs, and the expected safety profile of our
preclinical and investigational gene therapies. Any such statements
in this press release that are not statements of historical fact
may be deemed to be forward-looking statements. Results in
preclinical or early-stage clinical trials may not be indicative of
results from later stage or larger scale clinical trials and do not
ensure regulatory approval. You should not place undue reliance on
these statements, or the scientific data presented.
Any forward-looking statements in this press release are based
on AVROBIO’s current expectations, estimates and projections about
our industry as well as management’s current beliefs and
expectations of future events only as of today 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 any
one or more of AVROBIO’s product candidates will not be
successfully developed or commercialized, the risk of cessation or
delay of any ongoing or planned clinical trials of AVROBIO or our
collaborators, the risk that AVROBIO may not successfully recruit
or enroll a sufficient number of patients for our clinical trials,
the risk that AVROBIO may not realize the intended benefits of our
gene therapy platform, including the features of our plato®
platform, the risk that our product candidates or procedures in
connection with the administration thereof will not have the safety
or efficacy profile that we anticipate, the risk that prior
results, such as signals of safety, activity or durability of
effect, observed from preclinical or clinical trials, will not be
replicated or will not continue in ongoing or future studies or
trials involving AVROBIO’s product candidates, the risk that we
will be unable to obtain and maintain regulatory approval for our
product candidates, the risk that the size and growth potential of
the market for our product candidates will not materialize as
expected, risks associated with our dependence on third-party
suppliers and manufacturers, risks regarding the accuracy of our
estimates of expenses and future revenue, risks relating to our
capital requirements and needs for additional financing, risks
relating to clinical trial and business interruptions resulting
from the COVID-19 outbreak or similar public health crises,
including that such interruptions may materially delay our
enrollment and development timelines and/or increase our
development costs or that data collection efforts may be impaired
or otherwise impacted by such crises, and risks relating to our
ability to obtain and maintain intellectual property protection for
our product candidates. For a discussion of these and other risks
and uncertainties, and other important factors, any of which could
cause AVROBIO’s actual results to differ materially and adversely
from those contained in the forward-looking statements, see the
section entitled “Risk Factors” in AVROBIO’s most recent Annual or
Quarterly Report, as well as discussions of potential risks,
uncertainties and other important factors in AVROBIO’s subsequent
filings with the Securities and Exchange Commission. AVROBIO
explicitly disclaims any obligation to update any forward-looking
statements except to the extent required by law.
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Investors: Christopher F. Brinzey Westwicke, an ICR
Company 339-970-2843 chris.brinzey@westwicke.com
Media: Kit Rodophele Ten Bridge Communications
617-999-9620 krodophele@tenbridgecommunications.com
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