-- Study achieved statistical significance on all primary and
secondary biological endpoints --
Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage
biopharmaceutical company focused on the discovery and development
of precision genetic medicines to treat rare neuromuscular
diseases, today announced muscle biopsy results from its 4053-101
study, a Phase 1/2 first-in-human study conducted in Europe to
assess the safety, tolerability, pharmacokinetics, and efficacy of
golodirsen in 25 boys with confirmed deletions of the DMD gene
amenable to skipping exon 53. The study comprised two parts. In
Part 1, 12 patients were randomized to receive a dose titration of
golodirsen (8 patients) or placebo (4 patients). At the end
of Part 1 (dose titration), all 12 patients continued on golodirsen
and an additional 13 patients started golodirsen (Part 2). In
Part 2, all 25 patients were treated for an additional 48 weeks at
the time of muscle biopsy. The analysis included biopsies of the
bicep muscle at baseline and on-treatment at the Part 2 Week 48
time point. All 25 participants displayed an increase in skipping
exon 53 (p < 0.001) over baseline levels, representing a 100
percent response rate as measured by RT-PCR and demonstrating proof
of mechanism. Mean dystrophin protein increased to 1.019 percent of
normal compared to a mean baseline of 0.095 percent of normal (p
< 0.001) as measured by Western blot, the primary biological
endpoint in the study, representing a 10.7 fold increase from
baseline. The study also showed a statistically significant
increase in dystrophin immunofluorescence as measured by
immunohistochemistry (IHC), the secondary biological endpoint in
the study, confirming sarcolemma-associated protein expression and
distribution.
Francesco Muntoni, principal investigator for
this study and Pediatric Neurologist, Great Ormond Street Hospital
for Children NHS Foundation Trust and the UCL Great Ormond Street
Institute of Child Health, said, “All treated boys showed the
anticipated exon skipping after treatment and this resulted in a
mean increase of dystrophin protein, as measured by Western blot,
from 0.095 percent at baseline to 1.019 percent of normal after at
least one-year of treatment with golodirsen.”
“These data were also supported by the highly
statistically significant increase of dystrophin expression at the
sarcolemma, as measured by recently developed validated
methodology. This is now the second exon-skipping agent to have
shown a statistically significant increase in dystrophin
production, validating the exon-skipping approach to treating DMD
boys with amenable mutations.”
Professor Muntoni is also Director of the
Dubowitz Neuromuscular Center, a leading clinical and research
institution for children affected by neuromuscular disorders, and
Deputy Director, for the MRC Neuromuscular Translational Research
Centre at University College London.
“These data demonstrate statistically
significant exon skipping, dystrophin production and localization,
which further validate the broad application of our exon-skipping
platform and aligns with our strategic imperative to expand and
improve the treatment choices for the majority of patients with
DMD,” said Douglas Ingram, Sarepta Therapeutics’ president and
chief executive officer. “Additionally, the rigor with which we
designed our methods and executed this study speaks to our
commitment to continuous improvement and scientific
excellence.”
The full biological results from the 4053-101
study will be presented at an upcoming medical meeting or
scientific conference. Golodirsen is one of the investigational
candidates currently being evaluated in the ESSENCE study, a
global, randomized double-blind, placebo-controlled study
evaluating efficacy and safety in patients amenable to skipping
exons 45 or 53.
Dystrophin is a protein found in muscle cells
that, while present in extremely small amounts (about 0.002 percent
of total muscle protein), is crucial in strengthening and
protecting muscle fibers. A devastating and incurable
muscle-wasting disease, DMD is associated with specific errors in
the gene that codes for dystrophin, a protein that plays a key
structural role in muscle fiber function. Progressive muscle
weakness in the lower limbs spreads to the arms, neck and other
areas of the body. The condition is universally fatal, and death
usually occurs before the age of 30 generally due to respiratory or
cardiac failure.
Golodirsen uses Sarepta Therapeutics’
proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry
and exon-skipping technology to skip exon 53 of the DMD gene.
Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA,
resulting in exclusion, or “skipping”, of this exon during mRNA
processing in patients with genetic mutations that are amenable to
exon 53 skipping. Exon skipping is intended to allow for production
of an internally truncated dystrophin protein.
About the
4053-101 Study
The 4053-101 study was conducted as part of the
SKIP-NMD project, which was originally funded by a European Union
grant that allowed the completion of the first phase of the Phase
1/2 4053-101 study. In addition, the SKIP-NMD international project
was coordinated by Professor Muntoni and involved a consortium of
10 academic partners across Europe (UK, France, Belgium and Italy)
and the U.S. Several companies including Sarepta Therapeutics,
Consultants for Research and Imaging (CRIS), and SYSNAV (expertise
in indoor/outdoor robust navigation and positioning systems)
provided new advances and techniques in translational Duchenne
research, as did six patient organizations: Action Duchenne,
Association Française contre les Myopathies, Duchenne Family
Support Group, Duchenne Parent Project France, Duchenne Parent
Project Onlus, and Muscular Dystrophy UK.
The study is titled, “2-Part, Randomized,
Double-Blind, Placebo-Controlled, Dose-Titration, Safety,
Tolerability, and Pharmacokinetics Study (Part 1) Followed by an
Open-Label Efficacy and Safety Evaluation (Part 2) of SRP-4053 in
Patients With Duchenne Muscular Dystrophy Amenable to Exon 53
Skipping.”
Part 1 is a randomized, placebo-controlled
dose-titration to assess safety, tolerability and pharmacokinetics
of four dose levels of SRP-4053 in genotypically-confirmed DMD
patients with deletions amenable to exon 53 skipping.
Part 2 is an open-label evaluation of SRP-4053
in patients from Part 1, along with newly enrolled DMD patients
with deletions amenable to exon 53 skipping. Paired muscle biopsies
of the biceps brachii at baseline and on-treatment were obtained to
evaluate the biological endpoints from 25 patients treated with 30
mg/kg of SRP-4053 administered weekly by intravenous infusion
during Part 2 of the trial. The study is scheduled to continue for
144 weeks to evaluate safety and clinical endpoints.
About Duchenne Muscular
Dystrophy
DMD is an X-linked rare degenerative
neuromuscular disorder causing severe progressive muscle loss and
premature death. One of the most common fatal genetic disorders,
DMD affects approximately one in every 3,500 - 5,000 male births
worldwide.
About Sarepta
Therapeutics
Sarepta Therapeutics is a commercial-stage
biopharmaceutical company focused on the discovery and development
of precision genetic medicines 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 safety and efficacy of golodirsen
(SRP-4053); study data achieving statistical significance on
endpoints and validating Sarepta’s exon-skipping platform and
approach for the treatment of DMD boys with amendable mutations;
the data demonstrating statistically significant exon skipping,
dystrophin production and localization, which further validate the
broad application of Sarepta’s exon-skipping platform and align
with Sarepta’s strategic imperative to expand and improve the
treatment choices for the majority of patients with DMD; the rigor
with which Sarepta designed the methods and executed this study
speaking to Sarepta’s commitment to continuous improvement and
scientific excellence; the full biological results being presented
at an upcoming medical meeting or scientific conference; golodirsen
continued evaluation as part of the ESSENCE study and its designed
mechanism of action.
These forward-looking statements involve risks
and uncertainties, many of which are beyond Sarepta's control.
Known risk factors include, among others: the results of our
ongoing research and development efforts and clinical trials for
golodirsen (SRP-4053) and our other product candidates may not be
positive or consistent with these or prior results or demonstrate a
safe clinical benefit; 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; there may be
delays in Sarepta's projected development or regulatory timelines
for golodirsen (SRP-4053) and its other products candidates for
various reasons, some of which may be outside of Sarepta’s control,
including regulatory, court or agency decisions, and any or all of
Sarepta's product candidates may fail in development or may not
receive required regulatory approvals for commercialization; and
those risks identified under the heading “Risk Factors” in
Sarepta's 2016 Annual Report on Form 10-K or and most recent
Quarterly Report on Form 10-Q for the quarter ended June 30, 2017
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 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.
Source: Sarepta Therapeutics, Inc.
Media and Investors:
Sarepta Therapeutics, Inc.
Ian Estepan, 617-274-4052
iestepan@sarepta.com
or
W2O Group
Brian Reid, 212-257-6725
breid@w2ogroup.com
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