Sarepta Therapeutics Announces Eteplirsen Demonstrates a Continued Benefit on Walking Test Through 84 Weeks in Phase IIb Study

Sarepta Therapeutics Announces Eteplirsen Demonstrates a Continued Benefit on 
Walking Test Through 84 Weeks in Phase IIb Study in
Duchenne Muscular Dystrophy 
Data to Be Presented Today at the Wells Fargo Securities 2013
Healthcare Conference 
CAMBRIDGE, MA -- (Marketwired) -- 06/19/13 --  Sarepta Therapeutics,
Inc. (NASDAQ: SRPT), a developer of innovative RNA-based
therapeutics, today announced updated data from Study 202, a Phase
IIb open-label extension study of eteplirsen in patients with
Duchenne muscular dystrophy (DMD). Results at 84 weeks 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. Eteplirsen is Sarepta's lead
exon-skipping compound in development for the treatment of patients
with DMD who have a genotype amenable to skipping of exon 51. 
After 84 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 46.4 meters (p less than or equal to 0.045) when compared to the
placebo/delayed-treatment cohort (n=4). The eteplirsen-treated
patients in the mITT population demonstrated less than a 6 percent
decline (20.5 meters) from baseline in walking ability. After
experiencing a substantial decline earlier in the study, the
placebo/delayed-treatment cohort also demonstrated stabilization in
walking ability from Week 36 through 84, the period from which
meaningful levels of dystrophin were likely produced, with an
increase of 3.3 meters over this timeframe. These analyses were based
on the maximum 6MWT score when the test was performed on two
consecutive days. 
"We now have demonstrated stability of walking for over a year and a
half in the original eteplirsen treatment cohort in boys who are now
11 years old on average, an age when many DMD boys have lost the
ability to walk," said Chris Garabedian, president and chief
executive officer of Sarepta Therapeutics. "In addition, the
placebo/delayed-treatment cohort, which has now received eteplirsen
for over a year, has demonstrated a stabilization in walking ability
for 48 weeks compared with the precipitous decline observed earlier
in the study before dystrophin was confirmed in these patients.
Overall, we believe the data across all treatment cohorts are
remarkably consistent and continue to support eteplirsen as a
potential treatment option in DMD." 
Through 84 weeks, eteplirsen was well tolerated and there were no
clinically significant treatment-related adverse events, no serious
adverse events, hospitalizations or discontinuations.  
One boy in the placebo/delayed-treatment cohort was not able to
perform the 6MWT at the Week 84 clinic visit due to a physical injury
unrelated to treatment, and therefore had no 6MWT data captured at
the Week 84 time point. The boy has recovered from the injury,
continues to be ambulatory and is expected to be evaluated on the
6MWT at future clinic visits.  
Across all 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
strength. 
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: Eteplirsen versus Placebo/Delayed-Treatment to Week
84* 


 
-----------------------------------------------------------------
---------
                              Adjusted                                    
                              Mean                                        
Analysis of         Baseline  6MWT      Estimated Treatment               
Repeated 6MWT       6MWT      Change    Benefit (Eteplirsen  P-Value      
Values              (meters)  from      Minus                             
                              Baseline  Placebo/delayed-Tx)               
                              (meters)                                    
--------------------------------------------------------------------------
Maximum Score                                                             
Eteplirsen (n=6)    399.7     -20.5                          less than
--------------------------------------  46.4**               or equal to 
Maximum Score                                                0.045**       
Placebo/delayed-Tx  394.5     -66.8                                       
(n=4)                                                                     
--------------------------------------------------------------------------
Mean Score                                                                
Eteplirsen (n=6)    388.6     -9.2                           
--------------------------------------  43.2                 NS***         
Mean Score                                                                
Placebo/delayed-Tx  380.3     -52.5                                       
(n=4)                                                                     
--------------------------------------------------------------------------
Minimum Score                                                             
Eteplirsen (n=6)    377.5     2.0                            
--------------------------------------  40.1                 NS***        
Minimum Score                                                             
Placebo/delayed-Tx  366.0     -38.1                                       
(n=4)                                                                     
--------------------------------------------------------------------------
Day 1 Score                                                               
Eteplirsen (n=6)    379.7     -0.5                           
--------------------------------------  42.8                 NS***          
Day 1 Score                                                               
Placebo/delayed-Tx  371.5     -43.3                                       
(n=4)                                                                     
--------------------------------------------------------------------------

 
*   All 6MWT analyses are based on a Mixed Model Repeated Measures
test.
 **  The pre-specified primary analysis of the 6MWT results was
based on the maximum score.
 *** The lack of a 6MWT score at Week 84
for the one patient with a physical injury in the
placebo/delayed-treatment cohort, combined with the improvement seen
in the remaining boys in this cohort, resulted in the loss of
statistical significance in the additional 6MWT analyses (mean,
minimum, and day 1 value assessments). 
Mr. Garabedian will present these data today at the Wells Fargo 2013
Healthcare Conference at 1:50 p.m. in Boston, Mass. The presentation
will be webcast live under the investor relations section of the
Sarepta Therapeutics website at www.sareptatherapeutics.com and will
be archived there following the presentation for 90 days. 
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 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 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
expression.  
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. 
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 www.sareptatherapeutics.com. 
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. 
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 first quarter 10-Q, and filed with the
Securities and Exchange Commission. 
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. 
"Safe Harbor" Statement under the Private Securities Litigation
Reform Act of 1995: The statements that are not historical facts
contained in this release are forward-looking statements that involve
risks and uncertainties, including, but not limited to, the results
of research and development efforts, the results of preclinical and
clinical testing, the effect of regulation by the FDA and other
agencies, the impact of competitive products, product development,
commercialization and technological difficulties, and other risks
detailed in the company's Securities and Exchange Commission filings. 
Sarepta Investor Contact: 
Erin Cox 
857.242.3714 
ecox@sareptatherapeutics.com 
Sarepta Media Contact:
Jim Baker
857.242.3710
jbaker@sareptatherapeutics.com 
 
 
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