Eteplirsen, A Phosphorodiamidate Morpholino Oligomer (Pmo) For Duchenne Muscular Dystrophy (Dmd): Longitudinal Comparison To External Controls On Six-Minute Walk Test (6mwt) And Loss Of Ambulation (Loa)

DMD is a rare, degenerative, X-linked genetic disease that results in progressive muscle loss and premature death, which occurs in ~1:5000 males worldwide. DMD is primarily caused by whole exon deletions resulting in a shift of the dystrophin mRNA reading frame that prevents production of functional dystrophin protein. Eteplirsen, a PMO, is designed to skip exon 51, restore the reading frame, and induce production of internally-shortened dystrophin in patients amenable to exon 51-skipping. An analysis of 6MWT performance over 4 years compared boys treated with 30 or 50 mg/kg/wk eteplirsen IV (N = 12) versus a group of comparable, untreated external controls (N = 13) as defined by age, corticosteroid use, and genotype. At Year 4, a statistically significant treatment benefit of 162 meters on 6MWT was observed in eteplirsen-treated patients compared with external controls (p = 0.0005). Sensitivity analyses of 6MWT with covariates including baseline 6MWT, age and glucocorticoid use all resulted in differences >150 meters between the groups that were statistically significant (p < 0.01). Kaplan–Meier estimates of Loss of Ambulation (LOA) showed that 85% of the external control patients lost ambulation versus 17% of eteplirsen-treated patients at Year 4 (log-rank p = 0.011). Median age to LOA in the external cohort was 12.9 years. The eteplirsen-treated patients have not yet reached median age of LOA as 10/12 were still ambulatory at Year 4; however, the median age of the eteplirsen-treated boys at this time point was 13.4. Eteplirsen slows progression in DMD as evidenced by a 162 meter advantage on the 6MWT compared to the external control patients (p = 0.0005) at Year 4. In addition, there was a reduction in the risk of loss of ambulation in the eteplirsen treated patients (p = 0.011).