Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative
RNA-based therapeutics, today announced the publication of results from
two single ascending-dose studies that demonstrated no clinical or
toxicologic safety concerns with the company’s drug candidates for the
treatment of Ebola and Marburg virus, respectively. The study results
are to be published in the November issue of the American Society for
Microbiology’s journal, Antimicrobial Agents and Chemotherapy and
are available online at dx.doi.org/10.1128/AAC.03442-14.
AVI-6002 for the treatment of Ebola is a combination therapy of two
phosphorodiamidate morpholino oligomers (PMOs AVI-7537 and AVI-7539),
which target the viral matrix proteins VP24 and VP35, respectively.
AVI-6003 for the treatment of Marburg is a combination therapy of two
PMOs, (AVI-7287 and AVI-7288), which target the viral proteins VP24 and
NP, respectively. These drug candidates use Sarepta’s advanced and
proprietary PMOplus® chemistry, which is also
the basis of the company’s clinical-stage influenza drug candidate,
AVI-7100. Results from previous viral challenge studies of AVI-6002 and
AVI-6003 in non-human primates demonstrated prevention of disease
development and death following exposure to Ebola or Marburg virus.
Subsequent animal studies demonstrated that for each combination
therapy, only one oligomer contributed to efficacy, and therefore, the
lead drug candidates for Ebola and Marburg have since become the single
compounds AVI-7537 and AVI-7288.
“We believe these promising early clinical safety results, coupled with
the strong safety and efficacy data generated from animal studies for
all four PMO compounds, reinforce the use of our PMOplus®
chemistry platform to pursue potential treatments for deadly infectious
diseases such as Ebola and Marburg,” said Michael Wong, senior medical
director, infectious diseases at Sarepta Therapeutics. “We are
particularly encouraged to see results such as these in the healthy
human volunteers to what we have learned to be the effective agents,
AVI-7537 and AVI-7288. These compounds have protected up to 80-100
percent of the non-human primates to Ebola and Marburg virus challenge
infections, respectively.”
The two Phase I clinical studies were randomized, double-blind,
placebo-controlled trials designed to characterize the safety,
tolerability and pharmacokinetics of single doses of intravenous
formulations of AVI-6002 or AVI-6003 in healthy adult volunteers. In
each study, 30 subjects were enrolled in six cohorts receiving up to 9
mg/kg of the combination drug candidates (4 active:1 placebo per cohort)
for a total of 60 subjects. Results showed the compounds to be
well-tolerated with no dose limiting level demonstrated. No clinically
significant or dose-dependent effects were observed at any of the safety
endpoints evaluated. The safety and pharmacokinetics of the four PMOplus®
compounds comprising the two combination therapies were similar,
regardless of the target RNA sequence.
A previously reported Phase I MAD study of AVI-7288 for the treatment of
Marburg found no clinically significant or dose-dependent effects on any
of the safety endpoints evaluated when tested at up to 16 mg/kg/day for
14 days in healthy adult volunteers. The results of these clinical
studies add to a growing body of evidence supporting the safety of
Sarepta’s PMO-based chemistry platform across a broad range of disease
targets.
This work was conducted under contract with the Joint Product Management
Office of BioDefense Therapeutics (BD-Tx).
Works Cited
Antimicrob. Agents Chemother. November 2014 58:6639-6647; published
ahead of print 25 August 2014 , doi:10.1128/AAC.03442-14
Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino
Oligomers with Activity against Ebola Virus and Marburg Virus: Results
of Two Single-Ascending-Dose Studies
Alison E. Heald, Patrick L. Iversen, Jay B. Saoud, Peter Sazani, Jay S.
Charleston, Tim Axtelle, Michael Wong, William B. Smith, Apinya
Vutikullird, and Edward Kaye
About Sarepta's PMOplus® Chemistry
PMOplus® chemistry is an advanced generation of Sarepta's
phosphorodiamidate morpholino oligomer, or PMO, technology pioneered by
Sarepta. The PMO platform is designed to provide a stable chemistry
backbone with drug-like characteristics for Sarepta's advanced RNA-based
therapeutics. PMOplus® chemistry includes specific molecular
charges positionally inserted into the PMO's inherent charge-neutral
backbone.
About Sarepta Therapeutics
Sarepta is focused on developing first-in-class RNA-based therapeutics
to improve and save the lives of people affected by serious and
life-threatening rare and infectious diseases. The Company's diverse
pipeline includes its lead program eteplirsen and follow-on drug
candidates, for Duchenne muscular dystrophy, as well as potential
treatments for some of the world's most lethal infectious diseases.
Sarepta aims to build a leading, independent biotech company dedicated
to translating its RNA-based science into transformational therapeutics
for patients who face significant unmet medical needs. 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 use of
our PMOplusTM chemistry platform to pursue
potential treatments for deadly infectious diseases such as Ebola and
Marburg and the growing body of evidence supporting the safety of PMOs
across a broad range of disease targets.
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 and efficacy AVI-6002, AVI-6003
or any of Sarepta's drug candidates and/or Sarepta's PMO-based chemistry
platform; AVI-6002, AVI-6003 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 June 30,
3014 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.
Copyright Business Wire 2014