Sarepta Therapeutics Announces Publication of Eteplirsen Clinical Study Results in the Annals of Neurology

Sarepta Therapeutics Announces Publication of Eteplirsen Clinical Study Results 
in the Annals of Neurology 
Results Show a Significant Increase in Dystrophin Production and a
Stabilization of Walking Ability in Duchenne Muscular Dystrophy
CAMBRIDGE, MA -- (Marketwired) -- 08/08/13 --  Sarepta Therapeutics,
Inc. (NASDAQ: SRPT), a developer of innovative RNA-based
therapeutics, today announced the first peer-reviewed publication of
the 48-week results from the Phase IIb clinical study of eteplirsen
in the Annals of Neurology. Eteplirsen is an investigational medicine
in development for the treatment of patients with Duchenne muscular
dystrophy (DMD) who have a genotype amenable to skipping of exon 51. 
Published study results showed that once-weekly treatment with
eteplirsen resulted in a statistically significant increase from
baseline in novel dystrophin, the protein that is lacking in patients
with DMD. In addition, eteplirsen-treated patients evaluable on the
6-minute walk test (6MWT) demonstrated stabilization in walking
ability compared to a placebo/delayed-treatment cohort. Eteplirsen
was well tolerated in the study with no clinically significant
treatment-related adverse events. These data will form the basis of a
New Drug Application (NDA) to the U.S. Food and Drug Administration
(FDA) for eteplirsen planned for the first half of 2014. 
"These unprecedented data for eteplirsen in DMD patients with genetic
mutations correctable by skipping exon 51 represent a significant
milestone in the scientific community's efforts to address the
tremendous need for treatments for this devastating and deadly
disease in children," said Jerry Mendell, M.D., director of the
Centers for Gene Therapy and Muscular Dystrophy at Nationwide
Children's Hospital, principal investigator of the Phase IIb study
and lead author of the publication. "For the first time in this
disease, we have a potentially disease-modifying treatment that has
demonstrated strong evidence of a relationship between a biochemical
effect on dystrophin production and a clinically meaningful outcome
on the 6-minute walk test. In addition, we believe this technology
can potentially be applied to target additional genetic mutations in
DMD in the future." 
DMD is a rare degenerative neuromuscular disord
er that causes
progressive muscle loss, leading to severe disability and premature
death. It 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 leads to loss of
ambulation, limitations in activities of daily living, and serious
cardiac and respiratory dysfunction. The condition is universally
fatal, and patients typically die from complications of the disease
in their twenties. 
"The peer-reviewed publication of these data is an important
achievement as we continue to advance eteplirsen through late-stage
clinical development with the goal of bringing to patients and their
treating physicians a safe and effective therapy that addresses the
underlying cause of this devastating disease," said Edward Kaye,
M.D., senior vice president and chief medical officer of Sarepta
Therapeutics and a co-author of the publication. "The results
published today provide the foundation of efficacy and safety data
that we continue to build upon with our ongoing study of eteplirsen
in DMD patients, with consistent results now seen through 84 weeks of
treatment. We would like to thank all of the patients, families,
physicians and healthcare providers who have diligently worked on the
successful execution of this important clinical study of eteplirsen." 
Summary of the Phase IIb Study and Key Results Through Week 48 
The safety and efficacy of eteplirsen were evaluated in a 24-week
randomized, double-blind, placebo-controlled study (Study 201). The
study enrolled twelve boys aged seven to 13 years with a confirmed
genotype amenable to treatment with an exon-51 skipping drug. These
patients were randomized to one of three treatment arms including
placebo (n=4), eteplirsen 30 mg/kg (n=4) and eteplirsen 50 mg/kg
(n=4), and received eteplirsen or placebo weekly by intravenous
infusion. After 24 weeks, all placebo-treated patients initiated
weekly eteplirsen treatment at 30 mg/kg (n=2) or 50 mg/kg (n=2).
After Week 28, all patients were rolled over into a long-term
open-label extension study (Study 202), which continues to follow
patients on clinical and safety measures with data reported through
84 weeks. 
Dystrophin Production: The primary efficacy endpoint in Study 201 and
Study 202 was the change from baseline in the percent of
dystrophin-positive fibers present in muscle biopsies. Pre-treatment
muscle biopsies were collected from all patients in the study. To
evaluate the effect of eteplirsen dose and treatment duration on
dystrophin production, a second biopsy was collected at week 12 from
the four patients in the 50 mg/kg cohort and two placebo-treated
patients, and at Week 24 from the four patients in the 30 mg/kg
cohort and two placebo-treated patients. A third biopsy was collected
in all patients at Week 48. 
After 48 weeks of treatment, eteplirsen administered at either 30
mg/kg or 50 mg/kg for 48 weeks (n=8) resulted in a statistically
significant increase (p ≤ 0.001) in dystrophin-positive fibers
to 47.3 percent of normal. The placebo/delayed-treatment cohort,
which had received 24 weeks of eteplirsen at either 30 mg/kg or 50
mg/kg following 24 weeks of placebo (n=4), also showed a
statistically significant increase in dystrophin positive fibers to
37.7 percent of normal (p ≤ 0.008).  
Results from the study suggested that at least 12 weeks of treatment
was needed to observe increases in dystrophin production in muscle
biopsies. In addition, there was no meaningful difference in
dystrophin production between the 30 mg/kg and 50 mg/kg dose arms at
48 weeks. 
Walking Ability: A key secondary endpoint and the study's principal
clinical outcome measure was the 6-minute walk test, a standard and
well-accepted measure of walking ability and clinical function in
After 48 weeks, patients in the 30 mg/kg and 50 mg/kg dose cohorts
who were able to perform the 6MWT (modified Intent-to-Treat or mITT
population; n=6) showed a statistically significant treatment benefit
of 67.3 meters (p ≤ 0.001) when compared to the
placebo/delayed-treatment cohort (n=4). This difference exceeds the
28 to 44 meter treatment effect reported in clinical studies that
have served as a basis for the FDA approval of treatments for other
neuromuscular disorders. 
The mITT population used in the 6MWT analyses consisted of 10 of the
12 enrolled patients, including four patients in the 50 mg/kg cohort,
two patients in the 30 mg/kg cohort and four patients in the
placebo/delayed-treatment cohort. Two patients in the 30 mg/kg cohort
showed rapid disease progression upon enrollment and lost ambulation
by week 24, and thus were excluded. 
Safety: Through 48 weeks, eteplirsen was well tolerated and there
were no clinically significant treatment-related adverse events, no
serious adverse events, hospitalizations or discontinuations. 
About the Phase IIb Eteplirsen Program (Studies 201 and 202) 
Study 201 was a randomized, double-blind, placebo-controlled clinical
study initiated at Nationwide Children's Hospital in Columbus, Ohio.
Twelve boys aged 7 to 13 years with a confirmed genotype amenable to
treatment with an exon-51 skipping drug were randomized to one of
three cohorts: 30 mg/kg (n=4
), 50 mg/kg (n=4), and placebo/delayed
treatment (n=4). Eteplirsen and placebo were administered weekly by
intravenous infusion. 
At Week 25, all patients rolled over to Study 202, a long-term
open-label extension study, and placebo-treated patients initiated
eteplirsen treatment at 30 mg/kg (n=2) or 50 mg/kg (n=2). 
The primary efficacy endpoint in Study 201 and Study 202 was the
increase in novel dystrophin as assessed by muscle biopsy at Weeks 12
and 24 and at Week 48, respectively. The primary clinical endpoint
was the 6MWT, a well-accepted measure of ambulation and clinical
function in DMD. Long-term follow up in Study 202 continues to
evaluate safety and clinical outcomes including the 6MWT. 
About the 6-Minute Walk Test (6MWT) 
The 6-minute walk test (6MWT) was developed as an integrated
assessment of cardiac, respiratory, circulatory, and muscular
capacity (American Thoracic Society 2002) for use in clinical trials
of various cardiac and pulmonary conditions. In recent years the 6MWT
has been adapted to evaluate functional capacity in neuromuscular
diseases and has served as the basis for regulatory approval of a
number of drugs for rare diseases, with mean changes in the 6MWT
ranging from 28 to 44 meters (Rubin 2002, Wraith 2004, Muenzer 2006).
Additionally, published data from longitudinal natural history
studies assessing dystrophinopathy, a disease continuum comprised of
DMD and Becker muscular dystrophy, support the utility of the 6MWT as
a clinically meaningful endpoint (McDonald 2010) in DMD. These data
show that boys with DMD experience a significant decline in walking
ability compared to healthy boys over one year, suggesting that
slowing the loss of walking ability is a major treatment goal. 
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 boys worldwide. 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. Eventually,
increasing difficulty in breathing due to respiratory muscle
dysfunction requires ventilation support, and cardiac dysfunction can
lead to heart failure. The condition is universally fatal, and
patients typically die from complications of the disease in their
About Sarepta's Proprietary Exon-Skipping Platform Technology 
Eteplirsen is Sarepta's lead drug candidate and is designed to
address the underlying cause of DMD by enabling the production of a
functional dystrophin protein. Data from clinical studies of
eteplirsen in DMD patients have demonstrated a broadly favorable
safety and tolerability profile and restoration of dystrophin protein
Eteplirsen uses Sarepta's novel phosphorodiamidate morpholino
oligomer (PMO)-based chemistry and proprietary exon-skipping
technology to skip exon 51 of the dystrophin gene enabling the repair
of specific genetic mutations that affect approximately 13 percent of
the total DMD population. By skipping exon 51, eteplirsen may restore
the gene's ability to make a shorter, but still functional, form of
dystrophin from messenger RNA, or mRNA. Promoting the synthesis of a
truncated dystrophin protein is intended to stabilize or
significantly slow the disease process and prolong and improve the
quality of life for patients with DMD. 
Eteplirsen has been granted orphan drug designation by the FDA and
European Medicines Agency. 
Sarepta is also developing other PMO-based exon-skipping drug
candidates intended to treat additional patients with DMD. 
About Sarepta Therapeutics 
Sarepta Therapeutics 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, 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  
Forward-Looking Statements and Information 
This press release contains forward-looking statements. These
forward-looking statements generally can be identified by use of
words such as "believes or belief," "anticipates," "plans,"
"expects," "will," "intends," "potential," "possible," "advance" and
similar expressions. These forward-looking statements include
statements about the development of eteplirsen and its efficacy,
potency and utility as a potential treatment for DMD and the
potential for the creation of novel dystrophin to lead to significant
clinical benefit over a longer course of treatment, the sufficiency
of the Week 48 data as a basis for an NDA filing with the FDA and our
ability to provide the FDA with the additional information and data
that the FDA deems necessary for their regulatory determinations
regarding eteplirsen. 
Each forward-looking statement contained in this press release is
subject to risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by such statement.
Applicable risks and uncertainties include, among others: subsequent
clinical trials may fail to demonstrate the safety and efficacy of
eteplirsen or replicate results; treatment of patients with DMD using
eteplirsen over a longer duration may not lead to significant
clinical benefit; any of Sarepta's drug candidates, including
eteplirsen, may fail in development, may not receive required
regulatory approvals (including Subpart H accelerated approval), or
may not become commercially viable due to delays or other reasons;
and those identified under the heading "Risk Factors" in Sarepta's
Quarterly Report on Form 10-Q for the quarter ended June 30, 2013 and
other information Sarepta files with the Securities and Exchange
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 Securities and Exchange Commission. 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. 
Sarepta Investor Contact: 
Erin Cox 
Sarepta Media Contact:
Jim Baker
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