Sarepta Therapeutics Announces that at its First R&D Day, Jerry Mendell, M.D. Presented Positive Preliminary Results from the...
June 19 2018 - 10:28AM
-- Biopsies performed at Day 90 showed robust
micro-dystrophin expression in muscle measured by all methods and
observed in all three patients --
Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage
biopharmaceutical company focused on the discovery and development
of precision genetic medicine to treat rare neuromuscular diseases,
announced that at the Company’s R&D Day, Jerry Mendell, M.D. of
Nationwide Children’s Hospital presented positive preliminary
results from its Phase 1/2a gene therapy clinical trial assessing
AAVrh74.MHCK7.micro-Dystrophin in individuals with Duchenne
muscular dystrophy (DMD). Dr. Mendell presented the following
preliminary data on the first three patients enrolled in the study:
- All patients showed robust expression of transduced
micro-dystrophin, which is properly localized to the muscle
sarcolemma, as measured by immunohistochemistry. Mean gene
expression, as measured by percentage of micro-dystrophin positive
fibers was 76.2% and the mean intensity of the fibers was 74.5%
compared to normal control.
- All post-treatment biopsies showed robust levels of
micro-dystrophin as measured by Western blot, with a mean of 38.2%
compared to normal utilizing Sarepta’s method, or 53.7% compared to
normal pursuant to Nationwide Children’s quantification of
Sarepta’s method that adjusts for fat and fibrotic tissue.
- A mean of 1.6 vector copies per cell nucleus was measured in
patients, consistent with the high micro-dystrophin expression
levels observed.
- All patients showed significant decreases of serum creatine
kinase (CK) levels, with a mean reduction of CK of over 87% at Day
60. CK is an enzyme associated with muscle damage and patients with
DMD uniformly exhibit high levels of CK. Indeed, significantly
elevated CK is often used as a preliminary diagnosis tool for DMD,
which is then followed by confirmatory genetic testing.
- No serious adverse events (SAEs) were observed in the study.
Two patients had elevated gamma-glutamyl transferase (GGT) that
resolved with increased steroids within a week and returned to
baseline levels. There were no other significant laboratory
findings. Patients had transient nausea generally during the first
week of therapy coincident with increased steroid dosing.
Dr. Mendell, the study’s principal investigator,
in collaboration with Louise Rodino-Klapac, Ph.D., empirically
optimized the AAVrh74.MHCK7 specifically for DMD:
- The AAVrh74 vector can 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 neuromuscular diseases.
- As a rhesus monkey-derived AAV vector, AAVrh74 appears to show
lower immunogenicity rates in existing early-stage clinical studies
than expected with other 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 DMD, who typically die from pulmonary or cardiac
complications. In preclinical models, micro-dystrophin expression
in the heart was observed to be up to 120% of the micro-dystrophin
levels observed in skeletal muscles.
- The transgene was designed to maintain spectrin-like repeats 2
and 3, which has been reported to be important for maintaining the
protective functional characteristics of dystrophin.
“As a genetic medicine company, our goal is to
work with the world’s leading clinicians and scientists to advance
scientific discoveries to the clinic and, ultimately, to therapies
that profoundly improve and extend the lives of those living with
Duchenne muscular dystrophy and other rare, fatal diseases,” stated
Doug Ingram, Sarepta’s president and chief executive officer.
“Since the discovery of the dystrophin gene in 1986, scientists,
clinicians, patient advocates and the biotech ecosystem have
tirelessly searched for ways to restore or replace dystrophin and
rescue boys with DMD from the damage and early death. Dr. Mendell’s
results, if confirmed in additional patients, studies, measures and
time points, represent a monumental leap forward in the direction
of our goal.”
Dr. Mendell added, “I have been waiting my
entire 49-year career to find a therapy that dramatically reduces
CK levels and creates significant levels of dystrophin. Although
the data are early and preliminary, these results, if they persist
and are confirmed in additional patients, will represent an
unprecedented advancement in the treatment of DMD. I look forward
to treating more patients in the clinical study to generate the
data necessary to bring this therapy to patients with DMD, with the
goal of dramatically changing the course of the disease.”
“For years, PPMD has been interested in the
potential of gene therapy as a treatment for Duchenne. At a
critical moment in development in early 2017 – with the help and
support of our amazing community – we were thrilled to be able to
fund this important project of Drs. Mendell and Rodino-Klapac. To
have reached this moment today is incredible and we are grateful to
Sarepta for their investment and partnership in moving this
therapeutic approach forward. While these are early days and work
remains to fully understand the full potential of gene therapies,
these first signals are encouraging. We remain hopeful that this
will lead to a viable treatment for Duchenne,” stated Pat Furlong,
Parent Project Muscular Dystrophy’s (PPMD) founding president and
chief executive officer.
PPMD committed $2.2 million to the trial, with
support from additional Duchenne foundations and
families.
About Sarepta Therapeutics
Sarepta Therapeutics is a commercial-stage
biopharmaceutical company focused on the discovery and development
of precision genetic medicine to treat rare neuromuscular diseases.
The Company is primarily focused on rapidly advancing the
development of its potentially disease-modifying Duchenne muscular
dystrophy (DMD) drug candidates. 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 the design and potential benefits of
the AAVrh74 vector, including its ability to systemically and
robustly being delivered to skeletal, diaphragm and cardiac muscle
without promiscuously crossing the blood brain barrier and its
potential to show lower immunogenicity rates; the ability of the
MHCK7 promoter to robustly express in the heart; the potential of
the transgene to maintain the protective functional characteristics
of dystrophin; Sarepta’s goal to work with the world’s leading
clinicians and scientists to advance scientific discoveries to the
clinic and, ultimately, to therapies that profoundly improve and
extend the lives of those living with DMD and other rare, fatal
diseases; and the potential of Dr. Mendell’s results to represent a
monumental leap forward in the direction of Sarepta’s goal,
an unprecedented advancement in the treatment of DMD and
dramatically change the course of the disease.
These forward-looking statements involve risks
and uncertainties, many of which are beyond Sarepta’s control.
Actual results could materially differ from those stated or implied
by these forward-looking statements as a result of such risks and
uncertainties. 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; Sarepta’s ongoing
research and development efforts may not result in any viable
treatments suitable for commercialization due to a variety of
reasons, some of which may be outside of Sarepta’s control,
including the results of future research may not be consistent with
past positive results or may fail to meet regulatory approval
requirements for the safety and efficacy of product candidates,
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 Sarepta’s 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, 2017 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. 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.
Media and Investors: Sarepta Therapeutics, Inc. Ian Estepan,
617-274-4052 iestepan@sarepta.com or W2O Group Rachel Hutman,
301-801-5540 rhutman@w2ogroup.com
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