Sarepta Therapeutics Announces Eteplirsen Demonstrates Continued Stability on Walking Test Through 96 Weeks in Phase llb in Duchenne Muscular Dystrophy

We are encouraged by the promising Phase IIb data for eteplirsen, an exon-skipping compound, which we hope could be a breakthrough treatment for Duchenne muscular dystrophy. Currently, there is no treatment for this most common and lethal form of muscular dystrophy. While eteplirsen would likely work in only 15 percent of those with a specific gene mutation, the research behind the drug holds promise for finding effective treatments for all children living with Duchenne. CureDuchenne has played an important role in this progress by funding exon skipping research early on, and we continue to support this and other areas of research towards a cure.

See below for the Sarepta release that was distributed today.

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 days.

“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,” saidChris Garabedian, president and chief executive officer ofSarepta Therapeutics. “We look forward to sharing these updated data with theFDAas 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 discontinuations.

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 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: Week 96 Treatment Results*

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

* 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.

Edward M. Kaye, M.D., chief medical officer and senior vice president of Sarepta Therapeutics, will present these data on October 3at 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 days.

About the Phase IIb Eteplirsen Program (Studies 201 and 202)

Study 201 was a randomized, double-blind, placebo-controlled clinical study conducted atNationwide Children’s HospitalinColumbus, 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 Society2002) 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 (McDonald2010) 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 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 Therapeuticsis 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, 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 Cox857.242.3714 Email Contact
Sarepta Media Contact:Jim Baker 857.242.3710 Email Contact

Source:Sarepta Therapeutics, Inc.


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