Eteplirsen: Additional Phase IIb data

Additional data from 10 patients aged 7-13 with DMD in the modified intent-to-treat (mITT) population of the open-label Study 4658-US-202 extension of the double-blind, U.S. Phase IIb Study 4658-US-201 trial showed that patients who received either dose of eteplirsen for 74 weeks (30 or 50 mg/kg) had a 2.2 m reduction in mean 6MWT from baseline to week 74 compared to a 64.6 m reduction for patients who received placebo for 24 weeks followed by eteplirsen for an additional 50 weeks (p<=0.007). Mean baseline 6MWT scores were 388.6 m for the eteplirsen treatment group and 380.3 m for the placebo/delayed eteplirsen treatment group. Additionally, Sarepta said that patients in the placebo/delayed eteplirsen treatment group showed stabilization in walking ability (a <10 m decline) from week 36 through 74 - "the period in which meaningful levels of dystrophin were likely produced" - after experiencing a substantial decline earlier in the study. The mITT population excluded 2 twin patients who showed signs of rapid disease progression in the low-dose cohort in Study 4658-US-201 - both patients had a 6MWT score of <250 m at week 4 and neither could complete the 6MWT at week 24. Sarepta said that the mITT analysis was not prospectively defined but was conducted after the company found that the ITT analysis at 48 weeks was confounded by the 2 patients. Data will be presented at the Muscular Dystrophy Association meeting in Washington D.C. this month. Last quarter, Sarepta held an end-of-Phase II meeting with FDA to discuss seeking accelerated approval for eteplirsen. The company plans to begin dosing in a confirmatory study for eteplirsen in 1Q14, but has not yet finalized study details.

Last October, Sarepta reported data from Study 4658-US-202 showing that both doses of eteplirsen for 48 weeks met the primary endpoint of increasing the percentage of dystrophin-positive muscle fibers from baseline. In December, Sarepta reported 62 week data from the extension (see BioCentury, July 30. 2012; Oct. 8, 2012; & Dec. 17, 2012). In April 2012, Sarepta reported data from Study 4658-US-201 showing that 30 mg/kg IV eteplirsen met the primary endpoint of increasing dystrophin-positive muscle fibers as a percentage of normal from baseline to week 24 vs. placebo. Sarepta said the 50 mg/kg dose of eteplirsen did not significantly increase dystrophin-positive muscle fibers from baseline at week 12, suggesting that a longer duration of dosing is required before "meaningful levels" of dystrophin are produced (see BioCentury, April 9, 2012). ...