Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative
RNA-targeted therapeutics, today announced the publication of results
from a multiple ascending dose study to determine the safety of
AVI-7288, a PMOplus® antisense
oligonucleotide, in healthy adult volunteers, in the July 23, 2015 issue
of The New England Journal of Medicine. The results of the study,
conducted in collaboration with the U.S. Army Medical Research Institute
of Infectious Diseases (USAMRIID), demonstrated no clinical or
toxicologic safety concerns with AVI-7288, an investigational treatment
for Marburg Virus (MARV) infection. These results add to the continued
documentation of safety data for Sarepta’s PMO-based technology.
AVI-7288 utilizes Sarepta’s advanced and proprietary PMOplus®
technology. AVI-7288 is designed to bind to viral messenger RNA encoding
Marburg Virus nucleoprotein to inhibit nucleoprotein synthesis and
prevent viral replication and assembly. This mechanism of AVI-7288 is
fundamentally distinct from other RNA-based anti-infective therapies
that utilize a gene editing or degradation pathway. Additionally, this
approach highlights the flexibility and precision of the PMO-based
platform.
The Phase I clinical study was a randomized, double-blind,
placebo-controlled trial designed to characterize the safety,
tolerability and pharmacokinetics of AVI-7288 after daily repeat dosing.
Over 14 days, 40 healthy human volunteers (8 per dose group) were dosed
with up to 16 mg/kg/day, representing the highest continuous dosing of
any PMOplus® or any other antisense
oligonucleotide. This dosing also exceeded the predicted human
efficacious dose for AVI-7288 estimated by three different models based
upon nonhuman primate studies demonstrating up to 100% animal survival,
including in a delayed time to treat setting.
In healthy human volunteers, no significant safety concerns or
dose-dependent adverse side effects of AVI-7288 were reported with
respect to any safety end point evaluated, nor were any gross
abnormalities in renal function or biomarkers of renal dysfunction
observed. The maximum dose of AVI-7288 that could be administered
without raising significant safety concerns was not reached.
“These data add to the growing body of evidence underpinning the safety
profile of Sarepta’s PMO-based chemistry platform and its potential in
treating a variety of diseases.” stated Michael Wong, MD, Senior Medical
Director, Infectious Diseases. “We look forward to continuing to build
upon these data and further demonstrating the versatility and utility of
this novel precision medicine approach in tackling some of the most
challenging infectious disease threats today including pandemic
influenza and antimicrobial resistance.”
“Results described in this manuscript provide further confirmation that
PMO-based antisense therapeutics can protect against a highly pathogenic
virus in nonhuman primate disease models and, importantly, that the dose
regimen that we predict to be efficacious in humans is not likely to
compromise patient safety during treatment,” said Sina Bavari, Ph.D.,
USAMRIID Science Director.
This work was conducted under contract with the Department of Defense
Medical Countermeasures Systems/Joint Product Management Office of
BioDefense Therapeutics (BD-Tx).
Works Cited
N Engl J Med 2015;373;339-48; doi:10.1056/NEJMoa1410345
AVI-7288
for Marburg virus in nonhuman primates and humans.
Alison E. Heald,
Jay S. Charleston, Patrick L. Iversen, Travis K. Warren, Jay B. Saoud,
Mohamed Al-Ibrahim, Jay Wells, Kelly L. Warfield, Dana L. Swenson, Lisa
S. Welch, Peter Sazani, Michael Wong, Diane Berry, Edward M. Kaye, and
Sina Bavari.
About Sarepta's PMOplus® Chemistry
Platform
PMOplus® chemistry platform is an advanced generation of
Sarepta's phosphorodiamidate morpholino oligomer, or PMO, technology
pioneered by Sarepta. The PMO-based platform is designed to provide a
stable chemistry backbone with drug-like characteristics for Sarepta's
advanced RNA-targeted therapeutics. The PMOplus® chemistry
platform provides positionally specific positive molecular charges into
the inherently charge-neutral PMO.
About Sarepta Therapeutics
Sarepta Therapeutics is a biopharmaceutical company focused on the
discovery and development of unique RNA-targeted therapeutics for the
treatment of rare, infectious and other life threatening diseases. The
Company is primarily focused on rapidly advancing the development of its
potentially disease-modifying Duchenne muscular dystrophy (DMD) drug
candidates, including its lead DMD product candidate, eteplirsen,
designed to skip exon 51. Sarepta is also developing therapeutics for
the treatment of drug-resistant bacteria and infectious, rare and other
human diseases. For more information, please visit us at www.sarepta.com.
Forward Looking Statements
This press release contains "forward-looking statements" within the
meaning of the safe harbor provisions of the U.S. Private Securities
Litigation Reform Act of 1995. Any statements contained in this press
release that are not statements of historical fact may be deemed to be
forward-looking statements. Words such as "believes," "anticipates,"
"plans," "expects," "will," "intends," "potential," "possible" and
similar expressions are intended to identify forward-looking statements.
These forward-looking statements include statements regarding the safety
data and profile being collected on the use of PMO-based technology, the
mechanism and design of AVI-7288 and how they are distinct from other
RNA-based anti-infective therapies, the flexibility and precision of
Sarepta’s PMO-based platform and its potential in treating a variety of
diseases, Sarepta’s plans to add to the existing body of data and
demonstrate the versatility and utility of this novel precision medicine
approach in treating some of the most challenging infectious diseases
today (including influenza and antimicrobial resistance), and the
potential safety, efficacy and dosing of PMO-based therapeutics.
These forward-looking statements involve risks and uncertainties,
many of which are beyond Sarepta's control. Known risk factors include,
among others: clinical trials may not continue to be consistent with
prior results supporting the safety, efficacy or dosing of AVI-7288, any
of Sarepta's drug candidates and/or Sarepta's PMO-based chemistry
platform, AVI-7288 and any of Sarepta's drug candidates, including those
using Sarepta's PMO-based chemistry, may not be further developed by
Sarepta for various reasons, some of which may be outside of Sarepta's
control, may fail in development, may not receive required regulatory
approvals, or may not become commercially viable, and those additional
risks identified under the heading "Risk Factors" in Sarepta's Quarterly
Report on Form 10-Q for the Quarter ended March 31, 2015 and Annual
Report on Form 10-K for the year ended December 31, 2014 filed with the
Securities and Exchange Commission (SEC) and Sarepta's other filings
with the SEC.
Any of the foregoing risks could materially and adversely affect
Sarepta's business, results of operations and the trading price of
Sarepta's common stock. For a detailed description of risks and
uncertainties Sarepta faces, you are encouraged to review the Company's
filings with the SEC. We caution investors not to place considerable
reliance on the forward-looking statements contained in this press
release. Sarepta does not undertake any obligation to publicly update
its forward-looking statements based on events or circumstances after
the date hereof.
Internet Posting of Information
We routinely post information that may be important to investors in the
'For Investors' section of our website at www.sarepta.com.
We encourage investors and potential investors to consult our website
regularly for important information about us.
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