Sarepta Therapeutics Announces Eteplirsen Demonstrates Continued Stability on Walking Test Through 96 Weeks in Phase IIb Study

Sarepta Therapeutics Announces Eteplirsen Demonstrates Continued Stability on 
Walking Test Through 96 Weeks in Phase IIb Study in
Duchenne Muscular Dystrophy 
Data to Be Presented at the 18th International Congress of the World
Muscle Society 
CAMBRIDGE, MA -- (Marketwired) -- 09/26/13 --  Sarepta Therapeutics,
Inc. (NASDAQ: SRPT), a developer of innovative RNA-based
therapeutics, today announced data through Week 96 from Study 202, a
Phase IIb open-label extension study of eteplirsen in patients with
Duchenne muscular dystrophy (DMD). Results through nearly two years
showed a continued stabilization of walking ability in
eteplirsen-treated patients evaluable on the 6-minute walk test
(6MWT). As previously reported, Study 202 met its primary endpoint of
increased novel dystrophin as assessed by muscle biopsy at Week 48
and is now in the long-term extension phase in which patients
continue to be followed for safety and clinical outcomes.  
After 96 weeks, patients in the 30 mg/kg and 50 mg/kg eteplirsen
cohorts who were able to perform the 6MWT (modified Intent-to-Treat
or mITT population; n=6) experienced less than a 5 percent decline
(17.5 meters) from baseline in walking ability. A statistically
significant treatment benefit of 70.8 meters (p ≤0.001) was
observed for the mITT population compared with the
placebo/delayed-treatment cohort (n=4), which initiated treatment at
Week 25 following 24 weeks of placebo. After experiencing a
substantial decline earlier in the study, the
placebo/delayed-treatment cohort also demonstrated stabilization in
walking ability from Week 36 through 96, the period from which
meaningful levels of dystrophin were likely produced, with a decline
of 18.5 meters over this timeframe. These analyses were based on the
maximum 6MWT score when the test was performed on two consecutive
"We are very encouraged the study has demonstrated walking stability
in patients for more than a year since confirming that eteplirsen
treatment produced dystrophin in their muscles," said Chris
Garabedian, president and chief executive officer of Sarepta
Therapeutics. "We look forward to sharing these updated data with the
FDA as part of our New Drug Application for eteplirsen, which we plan
to submit in the first half of 2014." 
As previously reported, a boy in the placebo/delayed-treatment cohort
was not able to perform the 6MWT at the Week 84 clinic visit due to a
broken ankle assessed by the investigator as a treatment-unrelated
adverse event. Although this boy received rehabilitation and was able
to perform the 6MWT, his walking ability at the time of the test had
not returned to the level observed prior to the injury, and this
lower 6MWT distance contributed to the overall decline in the
placebo/delayed-treatment cohort. The decline in walking distance
observed in this cohort from Week 36 improves from a decline of 18.5
meters to a decline of 4.7 meters when this patient's 96-week test
score is excluded from the analysis.  
Through 96 weeks, eteplirsen was well tolerated and there were no
reported clinically significant treatment-related adverse events, no
treatment-related serious adverse events, hospitalizations or
Across patients in the eteplirsen and placebo/delayed-treatment
cohorts (Intent-to-Treat or ITT population), there is evidence of
continued stabilization on clinical laboratory tests,
echocardiograms, pulmonary function tests and measures of muscle
Summary of Additional 6MWT Analyses 
Patients performed two 6MWT evaluations on consecutive days at time
points coinciding with a muscle biopsy procedure at baseline and
Weeks 12, 24 and 48. All other evaluations were a single 6MWT. The
pre-specified primary analysis included the maximum distance walked
at those clinic visits where repeated tests were taken. Other
analyses of the repeated 6MWT results assessed mean, minimum, and Day
1 (first measure) scores. Results from these additional 6MWT analyses
confirm the robust treatment effect observed in the primary analysis. 
Summary of 6MWT: Week 96 Treatment Results* 

Analysis of       Baseline      Adjusted Mean   Benefit                     
Repeated 6MWT     6MWT          6MWT Change     (Eteplirsen     P-Value     
Values**          (meters)      from Baseline   Minus                       
                                (meters)        Placebo/delaye              
Maximum Score                                                               
Eteplirsen (n=6)  399.7         -17.5           70.8***         ≤0.001
Maximum Score                                                               
Placebo/delayed-  394.5         -88.3                                       
Tx (n=4)                                                                    
Mean Score                                                                  
Eteplirsen (n=6)  388.6         -6.3            67.7            ≤0.004
Mean Score                                                                  
Placebo/delayed-  380.3         -74.1                                       
Tx (n=4)                                                                    
Minimum Score                                                               
Eteplirsen (n=6)  377.5         4.7             64.5            ≤0.009
Minimum Score                                                               
Placebo/delayed-  366.0         -59.8                                       
Tx (n=4)                                                                    
Day 1 Score                                                                 
Eteplirsen (n=6)  379.7         2.3             67.2            ≤0.008
Day 1 Score                                                                 
Placebo/delayed-  371.5         -64.9                                       
Tx (n=4)                                                                    

* All 6MWT analyses are based on a Mixed Model Repeated Measures
 ** All 6MWT analyses include the mITT population
 *** The
pre-specified primary analysis of the 6MWT results was based on the
maximum score. 
Edward M. Kaye, M.D., chief medical officer and senior vice president
of Sarepta Therapeutics, will present these data on October 3 at the
18th International World Muscle Society (WMS) Congress at 2:30 p.m.
PDT at the Asilomar Conference Grounds in Pacific Grove, California.
The presentation will be archived in the investor relations section
of the Sarepta Therapeutics website at for 90 d
About the Phase IIb Eteplirsen Program (Studies 201 and 202) 
Study 201 was a randomized, double-blind, placebo-controlled clinical
study conducted 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 the Statistical Methodology and the Modified Intent-to-Treat
(mITT) Population  
The Mixed Model Repeated Measures (MMRM) test was used for all
statistical analyses of the 6MWT results. Baseline 6MWT scores and
duration since DMD diagnosis were included as covariates. 
The mITT population used in the 6MWT analyses consisted of 10 of the
12 enrolled patients, including 4 patients in the 50 mg/kg cohort, 2
patients in the 30 mg/kg cohort and 4 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. 
All other data including safety, echocardiogram, pulmonary function
tests, muscle strength measures and non-ambulatory functional tests
were analyzed for all 12 patients. 
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 born 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 str
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 death
usually occurs before the age of 30. 
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-skipp
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. 
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
ard-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, the potential
for the creation of ongoing novel dystrophin and its ability to lead
to significant clinical benefit over a longer course of treatment,
and the timing for regulatory submissions. 
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
Annual Report on Form 10-K for the full year ended December 31, 2012
and as updated by our 2013 second quarter 10-Q, and filed with the
Securities and Exchange Commission (SEC). 
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. 
Sarepta Investor Contact: 
Erin Cox 
Sarepta Media Contact:
Jim Baker
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