-- In two-month post-treatment muscle biopsies, clinical trial participants showed a mean of 51% beta-sarcoglycan
(beta-SG) positive fibers, as measured by immunohistochemistry (IHC), substantially exceeding the pre-defined 20% measure for
success --
-- Robust expression was also quantified by Western Blot and via intensity on IHC --
-- 90% mean creatine kinase (CK) reduction from baseline --
-- Participants received a dose of 5x1013 vg/kg --
CAMBRIDGE, Mass., Feb. 27, 2019 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in
precision genetic medicine for rare diseases, today announced positive results from three Limb-girdle muscular dystrophy (LGMD)
Type 2E clinical trial participants who received MYO-101. MYO-101 is a novel gene therapy intended to transduce skeletal and
cardiac muscle with a gene that codes for the full-length, native beta-SG protein, the lack of which causes LGMD2E. An autosomal
recessive muscular dystrophy, persons with LGMD2E begin showing neuromuscular symptoms such as difficulty running, jumping and
climbing stairs before age 10. The disease 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.
In Cohort 1 of the MYO-101 study, three participants ages 4-13, were treated with an infusion of MYO-101 at a dose
of 5x13vg/kg, with post-treatment biopsies taken at approximately two months. Preliminary results are as follows:
- All three participants in the study showed robust expression of transduced beta-SG, properly localized to the muscle
sarcolemma, as measured by IHC. The pre-defined measure of success for expression in the study was 20% positive fibers. Actual
mean protein expression, properly localized to the sarcolemma of the muscle, was 51%.
- Mean fiber intensity, as measured by IHC, was 47% compared to normal control.
- All participants showed robust quantification of beta-SG, as measured by Western blot, with mean beta-SG of 36.1% of normal
control.
- All participants showed a striking decrease in serum creatine kinase (CK) levels from pre-treatment baseline measure to last
measure, with a mean CK reduction of more than 90% from baseline. CK is an enzyme biomarker strongly associated with muscle
damage.
- Two participants had elevated liver enzymes, one of which was designated a serious adverse event (SAE), as the patient 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 quickly following supplemental steroid
treatment. There were no other clinically significant laboratory findings and no decreases in platelet counts were observed.
“LGMD2E is a devastating neuromuscular disease, currently lacking any treatment options,” said Jerry Mendell, M.D.,
Curran-Peters Chair of Pediatric Research at Nationwide Children’s Hospital and lead investigator for the study. “Results in
our first three clinical trial participants are consistent with what we have observed in preclinical models. We look forward
to continuing this pivotal trial focused on development of MYO-101 for LGMD2E.”
“The positive results in our first MYO-101 cohort strengthen our resolve to build out our gene therapy engine with
speed and purpose,” said Doug Ingram, Sarepta’s president and chief executive officer. “Our gene therapy constructs have now
produced high levels of expression of the missing protein of interest, and strong results in related biomarkers, in Duchenne and
LGMD2E, both cruel, fatal genetic diseases. And these results have potential read through to our other 4 LGMD programs and further
validate our gene therapy approach. Our success will come from the talent of our colleagues and our collaboration with the
industry’s best and brightest. In that vein, I would like to thank Dr. Jerry Mendell of Nationwide Children’s Hospital for his hard
work, ingenuity and extraordinary commitment to those living with rare neuromuscular disease.”
About MYO-101 and the Phase I/IIa Gene Transfer Clinical Trial
MYO-101 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 MYO-101 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 begins in muscles around the hips and shoulders before progressing to muscles in the arms and legs. Sarepta has five LGMD gene
therapy programs in development, including LGMD2E, LGMD2D, LGMD2C, LGMD2B and LGMD2L.
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 5 Limb-girdle muscular dystrophy diseases (LGMD),
Charcot-Marie-Tooth (CMT), 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 the potential of MYO-101 to transduce skeletal
and cardiac muscle with a gene that codes for the precise beta-SG protein; the results’ potential read through to our other 4 LGMD
programs; and Sarepta’s 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; 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,
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 opera-tions
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, 617-274-4052
iestepan@sarepta.com
Media:
Tracy Sorrentino, 617-301-8566
tsorrentino@sarepta.com
