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*
|Analysis of Repeated 6MWT Values†||Baseline 6MWT (meters)||Adjusted Mean 6MWTChange from Baseline(meters) at 120 Weeks||Estimated TreatmentBenefit (Eteplirsen MinusPlacebo/delayed-Tx)||P-Value|
|Maximum ScoreEteplirsen (n=6)||399.7||-13.9||64.9||0.006|
|Maximum ScorePlacebo/delayed-Tx (n=4)||394.5||-78.8|
|Mean ScoreEteplirsen (n=6)||388.6||-9.8||58.0||0.016|
|Mean ScorePlacebo/delayed-Tx (n=4)||380.3||-67.8|
|Minimum ScoreEteplirsen (n=6)||377.5||-5.7||51.0||0.042|
|Minimum ScorePlacebo/delayed-Tx (n=4)||366.0||-56.7|
|Day 1 ScoreEteplirsen (n=6)||379.7||+3.6||59.4||0.021|
|Day 1 ScorePlacebo/delayed-Tx (n=4)||371.5||-55.8|
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 DystrophyDMD 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.