Sarepta Therapeutics Announces Eteplirsen Meets Primary

Sarepta Therapeutics Announces Eteplirsen Meets Primary Endpoint of
Increased Novel Dystrophin and Achieves Significant Clinical Benefit
on 6-Minute Walk Test After 48 Weeks of Treatment in Phase IIb Study
in Duchenne Muscular Dystrophy 
Eteplirsen Results in an Increase in Novel Dystrophin to 47% of
Normal After 48 Weeks of Treatment; Eteplirsen 50mg/kg Weekly
Demonstrates Continued Clinical Benefit of 89.4 Meters in 6-Minute
Walk Test Over Placebo/Delayed Treatment Cohort; No
Eteplirsen-Related Adverse Events Through Week 48 
CAMBRIDGE, MA -- (Marketwire) -- 10/03/12 --  Sarepta Therapeutics
(NASDAQ: SRPT), a developer of innovative RNA-based therapeutics,
today announced that treatment with its lead exon-skipping compound,
eteplirsen, met the primary efficacy endpoint, increase in novel
dystrophin, and achieved a significant clinical benefit on the
primary clinical outcome, the 6-minute walk test (6MWT) over the
placebo/delayed treatment cohort in a Phase IIb extension trial in
Duchenne muscular dystrophy (DMD) patients.  
Eteplirsen administered once weekly 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 47.0% 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 38.3% of normal (p≤0.009).  
"These data represent a significant milestone and a defining moment
of progress and hope for patients with DMD and their families, as
well as for those of us in the scientific community who have been
pursuing potential treatments for this devastating and deadly disease
for decades," said Jerry Mendell, M.D., Director of the Centers for
Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital
and principal investigator of the Phase IIb study. Dr. Mendell added,
"By addressing the underlying cause of DMD, eteplirsen has
demonstrated unparalleled effects on enabling dystrophin production
and slowing the progression of the disease as measured by the
6-minute walk test, with no treatment associated adverse events.
While eteplirsen is targeted to DMD patients with a spec
ific genetic
mutation, I think the implications for all DMD patients with related
genetic mutations are clearly evident."  
Eteplirsen administered once weekly at 50 mg/kg over 48 weeks
resulted in an 89.4 meter benefit compared to patients who received
placebo for 24 weeks followed by 24 weeks of treatment with
eteplirsen in the open-label extension. In the predefined prospective
analysis of the study's intent-to-treat (ITT) population on the
primary clinical outcome measure, the change in 6MWT distance from
baseline, eteplirsen-treated patients who received 50 mg/kg of the
drug weekly (n=4) demonstrated an increase of 21.0 meters in distance
walked from baseline (mean=396.0 meters), while patients who received
placebo/delayed-eteplirsen treatment (n=4) showed a decline of 68.4
meters from baseline (mean=394.5 meters), for a statistically
significant treatment benefit of 89.4 meters over 48 weeks (p=0.016,
using ANCOVA for ranked data). There was no statistically significant
difference between the cohort of patients who received 30 mg/kg
weekly of eteplirsen and the placebo/delayed treatment cohort. 
"We are extremely excited about these data, as they demonstrate that
longer-term treatment with eteplirsen is translating to continued and
unprecedented increases in both dystrophin production and clinical
benefit across various subgroups of DMD patients involved in this
study," said Chris Garabedian, President and CEO of Sarepta
Therapeutics. "On a broader scale, these results signify the promise
and tremendous potential of our RNA-based technology to impact and
modulate disease at the genetic level, which may lead to first-ever
opportunities to target serious and life-threatening rare conditions
at the origin of disease."  
The safety profile of eteplirsen was evaluated across all subjects
through 48 weeks and there were no treatment-related adverse events,
no serious adverse events, and no discontinuations. Furthermore, no
clinically significant treatment-related changes were detected on any
safety laboratory parameters, including several biomarkers for renal
Summary of Dystrophin: Eteplirsen-Treated Patients in All Dose Groups
through Week 48* 

Treatment Arm                                Mean Change from   p-value     
                                             Baseline in %                  
                                             Positive Fibers                
Eterplirsen (both doses): 48 wks of Tx (n=8) 47.0               ≤0.001
  Eteplirsen 50 mg/kg (n=4)                  41.7               ≤0.008
  Eteplirsen 30 mg/kg (n=4)                  52.1               ≤0.001
Placebo/Delayed Tx: 24 wks of Tx (n=4)       38.3               ≤0.009
  Placebo/50 mg/kg Delayed-Tx (n=2)          42.9               ns          
  Placebo/30 mg/kg Delayed-Tx (n=2)          34.2               ns          

* Values based on Immunofluorescence using anti-dystrophin antibody
Modified Intent-to-Treat (mITT)  
The 6MWT results were further analyzed using the mITT population
which excluded two patients who were randomized to the 30 mg/kg
weekly eteplirsen cohort who showed signs of rapid disease
progression within weeks after enrollment and were unable to perform
measures of ambulation beyond 24 weeks. This mITT population
consisted of 10 patients (4 eteplirsen-treated patients receiving 50
mg/kg weekly, 2 eteplirsen-treated patients receiving 30 mg/kg
weekly, and 4 placebo/delayed-treatment patients).  
Summary of 6MWT: Eteplirsen versus Placebo/Delayed-Treatment to Week

Treatment Arm             Mean Change from   Estimated          p-value     
                          Baseline in 6MWT   Treatment Effect               
                          (meters)           (Eteplirsen minus              
Placebo/Delayed-Tx (n=4)  -60.3                                             
Eteplirsen 50 mg/kg (n=4) +27.1              87.4 m             ≤0.001
Eteplirsen Both Doses     +7.3               67.3 m             ≤0.001
Eteplirsen 30 mg/kg (n=2) -31.5              28.8 m             ns          

*Note: Analysis based on Mixed Model Repeated Measures test 
Summary of Additional Sub-Group Analyses at Week 48* 

Subset                    Mean 6MWT Change   Estimated          p-value     
                          from Baseline      Treatment Benefit              
                          (meters)           (Eteplirsen minus              
Placebo/delayed Tx:       -42.3              58.9 m             ≤0.038
< 9.5 yrs at baseline                                                       
(n=2; mean=7.6 yrs)                                                         
Eteplirsen:               +16.5                                             
< 9.5 yrs at baseline                                                       
(n=3; mean=8.4 yrs)                                                         
Placebo/delayed Tx:       -63.5              52.1 m             ns          
&#8805;9.5 yrs at                                                           
(n=2; mean=10.1 yrs)                                                        
Eteplirsen:               -11.3                                             
&#8805;9.5 yrs at                                                           
(n=3; mean=10.4 yrs)                                                        
Placebo/delayed Tx:       -53.5              93.8 m             &#8804;0.001
Higher 6MWT baseline                                                        
(n=2; mean=422m)                                                            
Eteplirsen:               +40.3                                             
Higher 6MWT baseline                                                        
(n=3; mean=424m)                                                            
Placebo/delayed Tx:       -65.8              39.6 m             ns          
Lower 6MWT baseline                                                         
(n=2; mean=367m)                                                            
Eteplirsen:               -26.2                                             
Lower 6MWT baseline                                                         
(n=3; mean=375m)                                                            
Placebo/delayed Tx:       -69.0              83.4 m             &#8804;0.001
Genotype 49-50 deletion                                                     
(n=3; age mean=9.2 yrs,                                                     
6MWT BL mean=397m)                                                          
Eteplirsen:               +14.4                                             
Genotype 49-50 deletion                                                     
(n=2; age mean=9.1 yrs,                                                     
6MWT BL mean=383m)                                                          

* Note: Analysis based on Mixed Model Repeated Measures test 
An abstract describing the results from this Phase IIb extension
study has been accepted as part of the World Muscle Society (WMS)
Congress's Late-Breaking Science program in Perth, Australia during
October 9 to October 13, 2012. Principal investigator, Jerry R.
Mendell, M.D. of Nationwide Children's Hospital, will present the
data via an oral presentation of the abstract titled, "Results at 48
Weeks of a Phase IIb Extension Study of the Exon-Skipping Drug
Eteplirsen in Patients with Duchenne muscular dystrophy (DMD)." Dr.
Mendell will present on October 13 at 4:00 p.m. WST UTC +8 hours/4:00
a.m. EDT. Dr. Mendell's presentation will be posted on the Sarepta
website in the "Events & Presentations" section after the session is
completed. In addition, Sarepta is sponsoring an educational
symposium at WMS chaired by Professor Steve Wilton, PhD, Head of the
Molecular Genetic Therapy Group and Director of Translational
Research and Development, Australian Neuromuscular Research Institute
at the University of Western Australia. Professor Wilton is a
long-time collaborator of Sarepta's whose groundbreaking research has
extended the use of antisense oligomers to DMD. 
About Study 201 and Study 202 (Phase IIb Eteplirsen Study)  
Study 4658-US-201 was conducted at Nationwide Children's Hospital in
Columbus, Ohio. Twelve boys meeting the inclusion criteria being
between 7 and 13 years of age with appropriate deletions of the
dystrophin gene that confirm eligibility for treatment with an
exon-51 skipping drug, received double-blind IV infusions of placebo
(n=4), 30 mg/kg of eteplirsen (n=4), or 50 mg/kg of eteplirsen once
weekly for 24 weeks (n=4). Muscle biopsies for evaluation of
dystrophin were obtained at baseline for all subjects, and after 12
weeks for patients in the 50 mg/kg cohort and after 24 weeks for
patients in the 30 mg/kg cohort. Two placebo patients were randomized
to the 30 mg/kg cohort and two placebo patients were randomized to
the 50 mg/kg cohort. This study design allowed Sarepta to investigate
the relationship of dose and duration of eteplirsen treatment on the
production of dystrophin over the course of the 24-week study. 
Study 4658-US-202 is the extension study to 201 and continues to
assess the long-term safety and efficacy of open-label eteplirsen.
The four placebo patients were rolled over to open-label eteplirsen
at week 24, with six patients on 30 mgs/kg, and six patients on 50
mgs/kg. Third biopsies occurred at 48 weeks in the original study 201
treated patients, and at 24 weeks, the same time point, in the
original placebo patients. 6MWT was performed at 32 weeks, 36 weeks,
48 weeks and will continue to be performed every 12 weeks going
About Dystrophin 
Dystrophin, a large structural protein, is critical to the stability
of myofiber membranes in skeletal, diaphragmatic and cardiac muscle,
protecting muscle fibers from contraction-induced damage. Loss of
functional dystrophin destabilizes the dystroglycan protein complex,
impairing its localization to the muscle membrane, and compromising
the integrity of the membrane structure. The absence of functional
dystrophin results in muscle membrane breakdown with muscle fibers
being replaced by adipose and fibrotic tissue. 
About the 6-Minute Walk Test  
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 dy
strophy, support the utility of the 6MWT as
a clinically meaningful endpoint (McDonald C, et al, Muscle & Nerve,
December 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 
The Mixed Model Repeated Measures (MMRM) test was used for all
statistical analyses of the 6MWT results, including for all
subgroups. Analysis of Covariance (ANCOVA) for ranked data was used
when the assumptions of normality of the dependent variable (the
change in 6MWT distance from baseline) were violated. The inclusion
of the two patients with extreme scores due to rapid progression in
the ITT population (n=12) resulted in a violation of the normality
assumptions of the Change from Baseline in 6MWT data, and thus
required the use of ANCOVA for ranked data. The exclusion of these
two patients from the mITT population (n=10) resulted in the 6MWT
data becoming normally distributed and the MMRM statistics exhibiting
much improved residuals and fit statistics as compared to the ITT
population. As such, the estimated mean values and their associated
p-values for the mITT population were slightly different from those
for the ITT population. 
Conference Call and Slide Show 
The Company will hold a conference call and broadcast a slide show
today at 8:00 a.m. EDT (5:00 a.m. PDT) to discuss these results. The
audio conference call may be accessed by dialing 866.356.3093 for
domestic callers and 617.597.5381 for international callers. The
passcode for the call is 93880948. Please specify to the operator
that you would like to join the "Sarepta Therapeutics 48-Week Results
Call." To view the slide show while using the audio dial-in please go
to the events section of Sarepta's website at The call and slide show will also be
webcast live under the events section and will be archived there
following the call for 90 days. Please connect to Sarepta's website
several minutes prior to the start of the broadcast to ensure
adequate time for any software download that may be necessary. An
audio replay will be available through October 10, 2012 by calling
888.286.8010 or 617.801.6888 and entering access code 67898748. 
About Duchenne Muscular Dystrophy and Eteplirsen 
Duchenne muscular dystrophy (DMD) is an X-linked rare, degenerative
neuromuscular disorder causing severe, progressive muscle loss and a
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 eventually spreads to the arms, neck and
other areas. Eventually, this progresses to complete paralysis and
increasing difficulty in breathing due to respiratory muscle
dysfunction requiring ventilatory support, as well as cardiac muscle
dysfunction leading to heart failure. The condition is terminal, and
death usually occurs before the age of 30. 
Eteplirsen is Sarepta's lead drug candidate that 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 improve, 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  
In order to provide Sarepta's investors with an understanding of its
current results and future prospects, this press release contains
statements that are forward-looking. 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 about the development of eteplirsen and its efficacy,
potency and utility in the treatment of DMD and the potential for the
creation of novel dystrophin to lead to significant clinical benefit
over a longer course of treatment.  
These forward-looking statements involve risks and uncertainties,
many of which are beyond Sarepta's control. Known risk factors
include, among others: clinical trials may not demonstrate the safety
and efficacy of eteplirsen and/or Sarepta's antisense-based
technology platform; treatment of patients with DMD using eteplirsen
over a longer duration may not lead to significant clinical benefit;
and any of Sarepta's drug candidates, including eteplirsen, may fail
in development, may not receive required regulatory approvals, or be
delayed to a point where they do not become commercially viable.  
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.
Sarepta does not undertake any obligation to publicly update its
forward-looking statements based on events or circumstances after the
date hereof.  
Sarepta Investor and Media Contact:
Erin Cox 
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