Baseline Performance on 6MWT Correlates with Other Functional Outcomes in a Phase IIb Study of Exon-Skipping Antisense Oligonucleotide Eteplirsen for Use in Duchenne Muscular Dystrophy (DMD) (P5.091)

OBJECTIVE: The objective of this analysis is to evaluate the correlations at Baseline between patients’ performance on the 6MWT and a variety of other functional measures. BACKGROUND: Duchenne Muscular Dystrophy is a degenerative X-linked genetic neuromuscular disorder with an incidence of 1 in 5,000 boys caused by mutations to the gene coding for the protein dystrophin. Patients’ qualifications for enrollment into clinical trials utilize several baseline functional measures before treatment initiation. DESIGN/METHODS: Twelve boys, aged 7 to 13 were randomized 1:1:1 to weekly IV infusion with 30mg/kg, 50mg/kg, or placebo/delayed treatment cohorts. Pearson correlation while controlling for patients’ age was used to evaluate the correlation between the maximum distance walked on the 6MWT administered at 2 consecutive days and the various functional outcomes (NSAA, rise time, 10-meter run time, timed 4-step test, FVC, FVC % predicted, MEP, and MIP) before treatment was initiated. RESULTS: Maximum distance walked on the 6MWT was statistically significantly correlated with rise time (r=-0.69), 10-meter run time (r=-0.65), FVC (r=-0.76), and MEP (r=-0.71). Moderate correlations were observed with NSAA (r=0.57, p≤0.07) and MIP (r=-0.54, p≤0.09). Correlations with the remaining functional measures failed to reach statistical significance with the lowest correlation observed with FVC % predicted (r=-0.25) and the timed 4-step test (r=-0.47). When the same variables were evaluated by using the Spearman rho coefficient (ranked data), both the NSAA and timed 4-step test became statistically significantly correlated with maximum distance walked. CONCLUSIONS: The high correlations evident among the various baseline measures suggest careful considerations to the patient selection criteria should be made at the time of designing study protocols. These findings suggest fewer criteria may be sufficient to qualify patients for clinical studies. Furthermore, and based on the mechanism of action of the experimental treatment, selecting a variety of uncorrelated measures for qualification may be warranted. Disclosure: Dr. Saoud has received personal compensation for activities with Sarepta Therapeutics as an employee. Dr. Mendell has received research support from Sarepta Therapeutics Inc. Dr. Rodino-Klapac has received research support from Sarepta Therapeutics. Dr. Sahenk has received research support from Sarepta Therapeutics. Dr. Roush has received research support from AVIBiopharma. Dr. Bird has nothing to disclose. Dr. Lowes has received personal compensation for activities with GlaxoSmithKline Inc. as a consultant. Dr. Lowes has received research support from Novartis. Dr. Alfano has nothing to disclose. Dr. Gomez Ramirez has nothing to disclose. Dr. Lewis has nothing to disclose. Dr. Malik has nothing to disclose. Dr. Shontz has nothing to disclose. Dr. Shilling has nothing to disclose. Dr. Sazani has received personal compensation for activities with Sarepta Therapeutics as an employee. Dr. Kaye has received personal compensation for activities with Sarepta Therapeutics as an employee.