Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision
genetic medicine for rare diseases, today announced the nine-month
functional results from three Limb-girdle muscular dystrophy Type
2E (LGMD2E) clinical trial participants who received SRP-9003.
SRP-9003 is an investigational gene therapy intended to transduce
skeletal and cardiac muscle with a gene that codes for the
full-length, native beta-sarcoglycan protein, the lack of which is
the sole cause of LGMD2E.
In Cohort 1 of the SRP-9003 study, three
participants ages 4-13 were treated with an infusion of SRP-9003 at
a dose of 5x1013vg/kg. Improvements in functional outcomes were
observed at day 270 (nine months) for all three participants.
“We have now observed consistent functional
improvements, in addition to high levels of expression of the
missing protein of interest and strong results in related
biomarkers, in both of our first cohorts for Duchenne muscular
dystrophy (SRP-9001) and LGMD2E (SRP-9003). We intend to test one
higher dose of SRP-9003 in LGMD2E participants, select our clinical
dose and then advance our SRP-9003 program, along with our other
five LGMD programs, as rapidly as possible,” said Doug Ingram,
Sarepta’s president and chief executive officer. “With the results
of our first LGMD2E cohort, Sarepta continues to build its gene
therapy engine, an enduring model created to design, develop and
bring to the medical and patient community transformative therapies
for those living with, and too often dying from, rare genetic
disease.”
At Day 270, mean creatine kinase (CK) was
significantly reduced compared to baseline. CK is an enzyme
biomarker strongly associated with muscle damage.
At Day 270, all three participants showed
improvements from baseline across all functional measures,
including the North Star Assessment for Dysferlinopathy (NSAD),
time to rise, four-stair climb, 100-m walk test and 10-meter walk
test. These results are distinctly different from what an
age-matched, natural history group would predict.
No new safety signals were observed and the
safety profile seen to date supports the ability to dose escalate
in the next cohort of the study. As previously disclosed, two
participants in the study had elevated liver enzymes, one of which
was designated a serious adverse event (SAE), as the participant
had associated transient increase in bilirubin. Both events
occurred when the participants were tapered off oral steroids and,
in both instances, elevated liver enzymes returned to baseline and
symptoms resolved following supplemental steroid treatment.
“LGMD2E is a devastating neuromuscular disease
with no current treatment options so we are very pleased to observe
a functional improvement in study participants who received
SRP-9003,” said Jerry Mendell, M.D., principal investigator at the
Center for Gene Therapy in the Abigail Wexner Research Institute at
Nationwide Children’s Hospital and lead investigator for the
study.
Sarepta had previously shared expression results
from the study, which found that in two-month post-treatment muscle
biopsies, clinical trial participants showed a mean of 51%
beta-sarcoglycan positive fibers, as measured by
immunohistochemistry (IHC), substantially exceeding the pre-defined
20% measure for success. Mean fiber intensity, as measured by
IHC, was 47% compared to normal control.
About SRP-9003 and the
Phase I/IIa Gene Transfer Clinical Trial
SRP-9003 uses the AAVrh74 vector, which is
designed to be systemically and robustly delivered to skeletal,
diaphragm and cardiac muscle without promiscuously crossing the
blood brain barrier, making it an ideal candidate to treat
peripheral neuromuscular diseases. As a rhesus monkey-derived AAV
vector, AAVrh74 has lower immunogenicity rates than reported with
other common human AAV vectors. The MHCK7 promoter has been chosen
for its ability to robustly express in the heart, which is
critically important for patients with LGMD2E, many of whom die
from pulmonary or cardiac complications.
This first-in-human study is evaluating a single
intravenous infusion of SRP-9003 among children with LGMD2E between
the ages of four and 15 years with significant symptoms of
disease.
About Limb-Girdle Muscular
Dystrophy
Limb girdle muscular dystrophies are genetic
diseases that cause progressive, debilitating weakness and wasting
that begin in muscles around the hips and shoulders before
progressing to muscles in the arms and legs.
Patients with LGMD2E begin showing neuromuscular
symptoms such as difficulty running, jumping and climbing stairs
before age 10. The disease, which is an autosomal recessive subtype
of LGMD, progresses to loss of ambulation in the teen years and
often leads to death before age 30. There is currently no treatment
or cure for LGMD2E.
Sarepta has five LGMD gene therapy programs in
development, including subtypes for LGMD2E, LGMD2D, LGMD2C, LGMD2B
and LGMD2L, and holds an option for a sixth program for LGMD2A.
About Sarepta
Therapeutics
Sarepta is at the forefront of precision genetic
medicine, having built an impressive and competitive position in
Duchenne muscular dystrophy (DMD) and more recently in gene
therapies for Limb-girdle muscular dystrophy diseases (LGMD), MPS
IIIA, Pompe and other CNS-related disorders, totaling over 20
therapies in various stages of development. The Company’s programs
and research focus span several therapeutic modalities, including
RNA, gene therapy and gene editing. Sarepta is fueled by an
audacious but important mission: to profoundly improve and extend
the lives of patients with rare genetic-based diseases. For more
information, please visit www.sarepta.com.
Forward-Looking Statements
This press release contains "forward-looking
statements." 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 our intention to test one higher dose
of SRP-9003 in LGMD2E participants, select our clinical dose and
then advance our SRP-9003 program, along with our other five LGMD
programs, as rapidly as possible; Sarepta continuing to build an
enduring gene therapy model created to design, develop and bring to
the medical and patient community transformative therapies for
those living with rare genetic disease; the safety profile of
SRP-9003 seen to date supporting the ability to dose escalate in
the next cohort of the study; SRP-9003 being an ideal candidate to
treat peripheral neuromuscular diseases; the potential benefits of
the AAVrh74 vector and the MHCK7 promoter; and our mission to
profoundly improve and extend the lives of patients with rare
genetic-based diseases.
These forward-looking statements involve risks
and uncertainties, many of which are beyond Sarepta’s control.
Known risk factors include, among others: success in preclinical
testing and early clinical trials, especially if based on a small
patient sample, does not ensure that later clinical trials will be
successful, and initial results from a clinical trial do not
necessarily predict final results; the data presented in this
release may not be consistent with the final data set and analysis
thereof or result in a safe or effective treatment benefit;
different methodologies, assumptions and applications Sarepta
utilizes to assess particular safety or efficacy parameters may
yield different statistical results, and even if Sarepta believes
the data collected from clinical trials of its product candidates
are positive, these data may not be sufficient to support approval
by the FDA or foreign regulatory authorities; Sarepta’s ongoing
research and development efforts may not result in any viable
treatments suitable for clinical research or commercialization due
to a variety of reasons, some of which may be outside of Sarepta’s
control, including possible limitations of company financial and
other resources, manufacturing limitations that may not be
anticipated or resolved for in a timely manner, and regulatory,
court or agency decisions, such as decisions by the United States
Patent and Trademark Office with respect to patents that cover our
product candidates; and even if Sarepta’s programs result in new
commercialized products, Sarepta may not achieve any significant
revenues from the sale of such products; and those risks identified
under the heading “Risk Factors” in Sarepta’s most recent Annual
Report on Form 10-K for the year ended December 31, 2018, and most
recent Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) as well as other SEC filings made by the
Company which you are encouraged to review.
Any of the foregoing risks could materially and
adversely affect the Company’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 SEC filings made by Sarepta. 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.
Source: Sarepta Therapeutics, Inc.
Sarepta Therapeutics, Inc.
Investors: Ian Estepan,
617-274-4052iestepan@sarepta.com
Media:Tracy Sorrentino,
617-301-8566tsorrentino@sarepta.com
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