Data Published in Molecular Therapy Demonstrate Five-Year Response Following a Single Dose of an Investigational Gene-Based T...
June 08 2017 - 7:00AM
Applied Genetic Technologies Corporation (NASDAQ:AGTC) and the
University of Massachusetts Medical School today announced the
publication of data demonstrating sustained protein expression five
years following a single intramuscular injection of a gene-based
therapy for the treatment of alpha-1 antitrypsin (AAT) deficiency.
The study, “5 Year Expression and Neutrophil
Defect Repair After Gene Therapy in Alpha-1 Antitrypsin Deficiency”
appears in the June issue of Molecular Therapy. AGTC developed the
gene-based therapy evaluated in the study, which was led by
researchers at the University of Massachusetts Medical School.
Alpha-1 antitrypsin deficiency is an inherited
genetic defect that results in severe loss of lung function. The
study describes five-year follow-up results of a one-time
intramuscular injection of a recombinant adeno-associated virus
(AAV)-AAT vector in patients with AAT deficiency who had
participated in a Phase 2a trial and had not received subsequent
AAT protein therapy. Key findings from the study include:
- Sustained expression of AAT protein over the five-year study
period without re-administration of AAV-AAT vector and in the
absence of immune suppression or corticosteroid therapy
- Partial correction of disease-associated defects in
neutrophils, a type of immune cell that contributes to lung damage
in patients with AAT, including neutrophil elastase inhibition,
markers of degranulation and membrane-bound anti-neutrophil
antibodies
- Evidence of an active regulatory T cell response that
contributed to stable gene expression despite the presence of an
immune response directed against the AAV vector
- Continuous, steady-state levels of AAT protein without the peak
and trough effects observed following infusion of AAT protein
replacement therapy
“This is the first publication to demonstrate
multi-year persistence of recombinant AAV expression in gene
therapy trial participants without immune suppression or
corticosteroid therapy,” said lead study investigator and senior
author Terence R. Flotte M.D., Dean of the School of Medicine,
Provost and Executive Deputy Chancellor, and The Celia and Isaac
Haidak Professor of Medical Education at the University of
Massachusetts Medical School. “We also observed specific regulatory
T cell responses directed against AAV1 capsid proteins, and believe
that these responses may help the immune system become tolerant to
AAV1. This would be beneficial in enabling the development of
AAV-based therapies for AAT deficiency that provide durable
responses following a single administration and may also allow for
repeat dosing regimens with potential to improve long-term outcomes
for patients with AAT deficiency. Finally, we have seen partial
correction of disease biomarkers resulting from sustained
expression of AAT in these patients.”
The authors conclude that stable levels of serum
AAT achieved in this study over five years may have beneficial
clinical effects, despite being below the threshold of what is
traditionally considered therapeutic. They hypothesize that
continuous expression at a lower level may provide greater clinical
benefit compared with levels that fluctuate drastically, as is
observed with current AAT replacement therapy. This is analogous to
the improvements observed in patients with diabetes receiving
continuous insulin infusions compared with those receiving multiple
daily insulin injections. Additional studies of intramuscular
administration of AAV-AAT will provide further insight into the
impact of AAT expression levels on symptoms of AAT deficiency.
“This study adds to the robust and growing body
of evidence supporting the clinical utility of AAV vectors produced
with AGTC’s proprietary manufacturing methods in the treatment of a
variety of diseases,” said Sue Washer, President and CEO of AGTC.
“We remain committed to evaluating the potential of our technology
to address unmet needs of patients with serious medical conditions,
and are proud to collaborate with leaders in clinical gene therapy,
including Dr. Flotte and his colleagues.”
About the University of Massachusetts
Medical School
The University of Massachusetts Medical School
in Worcester is a world-class research institution, consistently
producing noteworthy advances in clinical and basic research.
Researchers at UMMS have made pivotal advances in HIV, cancer,
diabetes, infectious disease, and in understanding the molecular
basis of disease. Programs and centers of international distinction
include those devoted to RNA therapeutics; gene therapy; gene
function and expression; systems biology; and ALS.
About AGTC
AGTC is a clinical-stage biotechnology company
that uses its proprietary gene therapy platform to develop products
designed to transform the lives of patients with severe diseases,
with an initial focus in ophthalmology. AGTC's lead product
candidates are designed to treat inherited orphan diseases of the
eye, caused by mutations in single genes that significantly affect
visual function and currently lack effective medical
treatments.
AGTC's product pipeline includes ophthalmology
programs in X-linked retinoschisis (XLRS), X-linked retinitis
pigmentosa (XLRP), achromatopsia, wet age-related macular
degeneration, and our optogenetics program with Bionic Sight.
AGTC's non-ophthalmology programs include its adrenoleukodystrophy
program and its otology program, which is in pre-clinical
development, and the company expects to advance several otology
product candidates into clinical development in the next few years.
Each of AGTC's XLRS, XLRP and adrenoleukodystrophy programs
is partnered with Biogen. AGTC employs a highly-targeted
approach to selecting and designing its product candidates,
choosing to develop therapies for indications having high unmet
medical need that it believes are clinically feasible and present
commercial opportunities. AGTC has a significant intellectual
property portfolio and extensive expertise in the design of gene
therapy products including capsids, promoters and expression
cassettes, as well as, expertise in the formulation, manufacture
and physical delivery of gene therapy products.
Forward Looking Statements
This release contains forward-looking statements
that reflect AGTC's plans, estimates, assumptions and beliefs.
Forward-looking statements include information concerning possible
or assumed future results of operations, business strategies and
operations, preclinical and clinical product development and
regulatory progress, potential growth opportunities, potential
market opportunities and the effects of competition.
Forward-looking statements include all statements that are not
historical facts and can be identified by terms such as
"anticipates," "believes," "could," "seeks," "estimates,"
"expects," "intends," "may," "plans," "potential," "predicts,"
"projects," "should," "will," "would" or similar expressions and
the negatives of those terms. Actual results could differ
materially from those discussed in the forward-looking statements,
due to a number of important factors. Risks and uncertainties that
may cause actual results to differ materially include, among
others: no gene therapy products have been approved in the United
States and only two such products have been approved in Europe;
AGTC cannot predict when or if it will obtain regulatory approval
to commercialize a product candidate; uncertainty inherent in the
regulatory review process; risks and uncertainties associated with
drug development and commercialization; factors that could cause
actual results to differ materially from those described in the
forward-looking statements are set forth under the heading "Risk
Factors" in the Company's Annual Report on Form 10-K for the fiscal
year ended June 30, 2016, as filed with the SEC. Given these
uncertainties, you should not place undue reliance on these
forward-looking statements. Also, forward-looking statements
represent management's plans, estimates, assumptions and beliefs
only as of the date of this release. Except as required by law, we
assume no obligation to update these forward-looking statements
publicly or to update the reasons actual results could differ
materially from those anticipated in these forward-looking
statements, even if new information becomes available in the
future.
IR/PR CONTACTS:
David Carey (IR) or Danielle Lewis (PR)
Lazar Partners Ltd.
T: (212) 867-1768 or (212) 843-0211
dcarey@lazarpartners.com or dlewis@lazarpartners.com
Mark Shelton
University of Massachusetts Medical School
T: (508) 856-5841 or (508) 856-2000
Mark.Shelton@umassmed.edu
CORPORATE CONTACTS:
Larry Bullock
Chief Financial Officer
Applied Genetic Technologies Corporation
T: (386) 462-2204
lbullock@agtc.com
Stephen Potter
Chief Business Officer
Applied Genetic Technologies Corporation
T: (617) 413-2754
spotter@agtc.com
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