The Lancet Publishes Clinical Trial Data That Demonstrate Statistically Significant and Dose-Dependent Expression of Dystrophin
July 25 2011 - 7:00AM
Marketwired
AVI BioPharma, Inc. (NASDAQ: AVII), a developer of RNA-based
therapeutics, today announced that data published in The Lancet
from a Phase 1b/2 study of eteplirsen, the Company's exon-skipping
therapy for the treatment of Duchenne muscular dystrophy (DMD),
demonstrate that the treatment was well tolerated and was shown to
induce statistically significant and dose-dependent improvements in
dystrophin expression in patients. DMD is a genetic muscle wasting
disease caused by the absence of functional dystrophin, an
essential muscle protein.
"Our observations of significant and dose dependent improvements
in novel dystrophin expression and other associated biochemical
markers suggest that eteplirsen has the potential to reduce muscle
damage in DMD patients and positively modify the severe progressive
nature of the disease," said Prof. Francesco Muntoni, professor of
pediatric neurology and head of the Dubowitz Neuromuscular Centre
at the UCL Institute of Child Health, London, and the corresponding
author of the study paper. "Restoration of dystrophin with a safe
therapeutic candidate could have a considerable positive impact on
the quality of life for patients, their mobility and the way their
condition is managed as they age, and we are eager to continue the
investigation of eteplirsen in placebo-controlled trials to
evaluate biochemical markers and clinical endpoints over a longer
treatment duration."
The primary objective of the 19-patient, 12-week, six dose
cohort study was to assess eteplirsen's safety and tolerability.
Secondary objectives were assessments of the pharmacokinetic
profile and ability to restore dystrophin expression. Eteplirsen
was well tolerated in all patients, with no clear drug-related
serious adverse events. Reported adverse events were mostly mild or
moderate in intensity and not dose-related. The plasma half-life
was short, and there was no plasma accumulation observed between
doses. Clearance of eteplirsen was primarily via the kidney.
Eteplirsen induced exon 51 skipping in all cohorts, and novel
dystrophin protein expression was observed in a dose-dependent
manner (p=0.02). While results were variable among patients, the
substantial, statistically significant (p=0.04), new dystrophin
expression was observed in the highest two dose cohorts. Moreover,
novel dystrophin expression was accompanied by a significant
reduction of inflammatory cell infiltrates in the two highest dose
cohorts, including CD3 (p=0.01), CD4 and CD8 inflammation markers,
suggesting an alteration in the underlying degenerative disease
process. The functional properties of the novel dystrophin
expression were confirmed by localization of the protein at the
sarcolema, or cell membrane. Clinical muscle function evaluations
found that most patients remained stable during the study period.
The study was not designed to evaluate clinical benefit, and longer
drug exposure is believed necessary to influence disease
progression.
Chris Garabedian, AVI's CEO and president, commented: "The
publication of our most recent clinical trial data in The Lancet
reinforces the commitment we made to accelerate our development of
eteplirsen. We are more focused than ever on optimizing our
development efforts and continue to advance the NDA-enabling
activities initiated earlier this year to support the start of a
pivotal trial."
About Duchenne Muscular Dystrophy
DMD is one of the most common fatal genetic disorders to affect
children around the world. Approximately one in every 3,500 boys
worldwide is affected with DMD. A devastating and incurable
muscle-wasting disease, DMD is associated with specific inborn
errors in the gene that codes for dystrophin, a protein that plays
a key structural role in muscle fiber function. Progressive muscle
weakness eventually spreads to the arms, neck and other areas.
Eventually, this progresses to complete paralysis and increasing
difficulty in breathing due to respiratory muscle dysfunction
requiring ventilatory support as well as cardiac muscle dysfunction
leading to heart failure. The condition is terminal, and death
usually occurs before the age of 30.
About Eteplirsen
Eteplirsen is AVI's lead drug candidate that is systemically
delivered for the treatment of a substantial subgroup of patients
with DMD. Data from clinical studies of eteplirsen in DMD patients
have demonstrated a broadly favorable safety and tolerability
profile and restoration of dystrophin protein expression and other
markers of biochemical efficacy.
Eteplirsen uses AVI's novel phosphorodiamidate morpholino
oligomer (PMO)-based chemistry and proprietary exon-skipping
technology to skip exon 51 of the dystrophin gene. By skipping exon
51, eteplirsen may restore the gene's ability to make a shorter,
but still functional, form of dystrophin from mRNA. Promoting the
synthesis of a truncated dystrophin protein is intended to improve,
stabilize or significantly slow the disease process and prolong and
improve the quality of life for patients with DMD. AVI is also
developing other PMO-based exon-skipping drug candidates intended
to treat additional patients with DMD.
About AVI BioPharma
AVI BioPharma is focused on the discovery and development of
novel RNA-based therapeutics for rare and infectious diseases, as
well as other select disease targets. Applying pioneering
technologies developed and optimized by AVI, the Company is able to
target a broad range of diseases and disorders through distinct
RNA-based mechanisms of action. Unlike other RNA-based approaches,
AVI's technologies can be used to directly target both messenger
RNA (mRNA) and precursor messenger RNA (pre-mRNA) to either
down-regulate (inhibit) or up-regulate (promote) the expression of
targeted genes or proteins. By leveraging a highly differentiated
RNA-based technology platform, AVI has built a pipeline of
potentially transformative therapeutic agents, including
eteplirsen, which is in clinical development for the treatment of
Duchenne muscular dystrophy, and multiple drug candidates that are
in clinical development for the treatment of infectious diseases.
For more information, visit www.avibio.com.
Forward-Looking Statements and
Information
This press release contains statements that are forward-looking,
including statements about the development of AVI's product
candidates, including the initiation of a pivotal study for
eteplirsen, and the efficacy, potency and utility of our product
candidates in the treatment of rare and infectious diseases. These
forward-looking statements involve risks and uncertainties, many of
which are beyond AVI's control. Known risk factors include, among
others: clinical trials may not demonstrate safety and efficacy of
any of AVI's drug candidates and/or AVI's antisense-based
technology platform; any of AVI's drug candidates may fail in
development, may not receive required regulatory approvals, or be
delayed to a point where they do not become commercially viable.
Any of the foregoing risks could materially and adversely affect
AVI's business, results of operations and the trading price of its
common stock. For a detailed description of risks and uncertainties
AVI faces, you are encouraged to review the official corporate
documents filed with the Securities and Exchange Commission. AVI
does not undertake any obligation to publicly update its
forward-looking statements based on events or circumstances after
the date hereof.
"Safe Harbor" Statement under the Private Securities Litigation
Reform Act of 1995: The statements that are not historical facts
contained in this release are forward-looking statements that
involve risks and uncertainties, including, but not limited to, the
results of research and development efforts, the results of
preclinical and clinical testing, the effect of regulation by the
FDA and other agencies, the impact of competitive products, product
development, commercialization and technological difficulties, and
other risks detailed in the company's Securities and Exchange
Commission filings.
AVI Investor and Media Contact: David Schull Russo Partners
858.717.2310 or 212.845.4271 Email Contact
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