Jul 24, 2012 (Marketwire via COMTEX) --Sarepta Therapeutics (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced that treatment with its exon-skipping compound, eteplirsen, achieved a significant clinical benefit on the primary clinical outcome, the 6-minute walk test (6MWT), over a placebo/delayed treatment cohort in a Phase IIb trial in Duchenne muscular dystrophy (DMD) patients. Eteplirsen administered once weekly at 50mg/kg over 36 weeks resulted in a 69.4 meter benefit compared to patients who received placebo for 24 weeks followed by 12 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 50mg/kg of the drug weekly (n=4) demonstrated a decline of 8.7 meters in distance walked from baseline (mean=396.0 meters), while patients who received placebo/delayed-eteplirsen treatment for 36 weeks (n=4) showed a decline of 78.0 meters from baseline (mean=394.5 meters), for a statistically significant treatment benefit of 69.4 meters over 36 weeks (p≤0.019).

"The magnitude of this clinical benefit is an unprecedented treatment effect in DMD. This result represents a major advance in the pursuit of a disease modifying treatment for this severe, progressive and life-threatening disease," 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, "The 6-minute walk test results with eteplirsen, combined with its safety profile to date, make eteplirsen the most promising advance to treat the underlying cause of muscular dystrophy I've seen in my more than 30 years in the field."

The clinical benefit observed in the 50mg/kg treatment cohort compared to placebo was also significant at week 32 with a benefit of 59.9 meters (p≤0.045). The safety profile of eteplirsen was evaluated across all subjects through 36 weeks and there were no treatment-related adverse events, no serious adverse events and no discontinuations. Furthermore, no treatment related changes were detected on any safety laboratory parameters, including several biomarkers for renal function.

"These data suggest that the previously reported levels of dystrophin we observed in muscle biopsies after 24 weeks of treatment are translating to a clinical benefit on the standard measure of ambulation in DMD patients," said Chris Garabedian, President and CEO of Sarepta Therapeutics. "The magnitude of this 69.4-meter difference after 36 weeks of treatment and the robustness of the statistical analysis is encouraging, especially given the average benefit in the 6-minute walk test for several approved drugs in other diseases has been 30 to 40 meters." 

There was no statistically significant difference between the cohort of patients who received 30mg/kg weekly of eteplirsen and the placebo/delayed treatment cohort.

Modified Intent-to-Treat and Subgroup Analyses

A modified intent-to-treat (mITT) population was evaluated that excluded two patients who were randomized to the 30mg/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 consisting of 10 patients (4 eteplirsen-treated patients receiving 50mg/kg weekly, 2 eteplirsen-treated patients receiving 30mg/kg weekly, and 4 placebo/delayed-treatment patients) was further analyzed.

Summary of 6MWT: Eteplirsen versus Placebo/Delayed-treatment through Week 36*

*Note: Analysis based on Mixed Model Repeated Measures test

Summary of Additional Sub-Group Analyses at Week 36**

 ** Note: Analysis based on Mixed Model Repeated Measures test

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 will occur 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 and 36 weeks, and will continue to be performed every 12 weeks going forward.