Eteplirsen: Additional Phase IIb data

Additional data from 10 patients age 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 168 weeks (30 or 50 mg/kg) had a 72.9 meter reduction in mean 6MWT from baseline to week 168 compared to a 135.9 meter reduction for patients who received placebo for 24 weeks followed by eteplirsen for an additional 144 weeks (p=0.023). Mean baseline 6MWT scores were 388.6 meters for the eteplirsen treatment group and 380.3 meters for the placebo/delayed eteplirsen treatment group.

In the ITT population (n=12), eteplirsen increased mean maximum inspiratory pressure (MIP) by 11.1% and mean maximum expiratory pressure (MEP) by 13.5% from baseline to week 168. MIP and MEP are measures of respiratory muscle function. Eteplirsen decreased MIP percent predicted (MIP adjusted for weight) by 2.4% and reduced MEP percent predicted (MEP adjusted for age) by 6.3% from baseline to week 168. Additionally, eteplirsen increased mean forced vital capacity (FVC) by 11.6% from baseline to week 168. FVC percent predicted (FVC adjusted for age and height) was 101.3% at baseline and 91.9% at week 168. The mITT population excluded a set of 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 meters 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. ...