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Sarepta Therapeutics Announces Eteplirsen Demonstrates Continued Stability on Walking Test through 120 Weeks in Phase IIb Study

  Sarepta Therapeutics Announces Eteplirsen Demonstrates Continued Stability
  on Walking Test through 120 Weeks in Phase IIb Study in Duchenne Muscular
  Dystrophy

Company to present today at the 32nd Annual J.P. Morgan Healthcare Conference

JPMorgan Healthcare Conference 2014

Business Wire

CAMBRIDGE, Mass. -- January 15, 2014

Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative RNA-based
therapeutics, today announced data through Week 120 from Study 202, a Phase
IIb open-label extension study of eteplirsen in patients with Duchenne
muscular dystrophy (DMD). Results through more than 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.

At 120 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 a decline of 13.9 meters, or less than 5 percent, from
baseline in walking ability. A statistically significant treatment benefit of
64.9 meters (p ≤0.006) 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 for more than 1.5 years, from Week 36 through
120, the period from which meaningful levels of dystrophin were likely
produced, with a decline of 9.5 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 more than two years of data with eteplirsen on the 6-minute walk
test, the most accepted clinical outcome measure in Duchenne muscular
dystrophy, which demonstrates walking stability that we believe would not be
expected based on the natural history of this disease over the same time
period,” said Chris Garabedian, president and chief executive officer of
Sarepta Therapeutics. “We also now have over two years of safety data with
eteplirsen with no treatment-related serious adverse events which is important
when considering the need for lifelong treatment of this disease.”

Through 120 weeks, eteplirsen was well tolerated and there were no reported
clinically significant treatment-related adverse events and no
treatment-related serious adverse events. In addition, there were no
treatment-related hospitalizations or discontinuations.

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.
Two 6MWT evaluations were also performed at Week 120, and will be performed at
all future functional assessment visits. 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 treatment
effect observed in the primary analysis.

Summary of 6MWT: Week 120 Treatment Results*

                                                                 
                                        Adjusted
                                        Mean
                                        6MWT           Estimated Treatment
Analysis of              Baseline       Change         Benefit (Eteplirsen
Repeated 6MWT         6MWT        from        Minus                  P-Value
Values†                  (meters)       Baseline       Placebo/delayed-Tx)
                                        (meters)
                                        at 120
                                        Weeks
Maximum Score         399.7       -13.9                             
Eteplirsen (n=6)
Maximum Score                                          64.9                      0.006
Placebo/delayed-Tx    394.5       -78.8                             
(n=4)
Mean Score            388.6       -9.8
Eteplirsen (n=6)
Mean Score                                             58.0                      0.016
Placebo/delayed-Tx    380.3       -67.8                             
(n=4)
Minimum Score         377.5       -5.7
Eteplirsen (n=6)
Minimum Score                                          51.0                      0.042
Placebo/delayed-Tx    366.0       -56.7                             
(n=4)
Day 1 Score           379.7       +3.6
Eteplirsen (n=6)
Day 1 Score                                            59.4                      0.021
Placebo/delayed-Tx    371.5       -55.8                             
(n=4)
                                 

* All 6MWT analyses are based on a Mixed Model Repeated Measures test.

† All 6MWT analyses include the mITT population

‡ The pre-specified primary analysis of the 6MWT results was based on the
maximum score.

Mr. Garabedian will present these data today at the 32^nd Annual J.P. Morgan
Healthcare Conference at 4:30 p.m. PST (7:30 p.m. EST) in San Francisco,
California. The presentation will be webcast live under the investor relations
section of Sarepta's website at www.sarepta.com and will be archived there 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.

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 since they
were no longer evaluable for the 6MWT. All other data 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 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.sarepta.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, the potential
for the creation of ongoing novel dystrophin and its ability to lead to
significant clinical benefit, including as measured by the 6MWT and
exploratory measures, 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, including as measured by the 6MWT and
exploratory measures; 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 during projected time frames or at all 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 third 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.

Contact:

Sarepta Investor Contact:
Erin Cox, 857-242-3714
ecox@sarepta.com
or
Sarepta Media Contact:
Jim Baker, 857-242-3710
jbaker@sarepta.com
 
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