OBJECTIVE: In prior open-label studies, eteplirsen, a phosphorodiamidate 
morpholino oligomer, enabled dystrophin production in Duchenne muscular 
dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present 
study used a double-blind placebo-controlled protocol to test eteplirsen's 
ability to induce dystrophin production and improve distance walked on the 
6-minute walk test (6MWT).
METHODS: DMD boys aged 7 to 13 years, with confirmed deletions correctable by 
skipping exon 51 and ability to walk 200 to 400 m on 6 MWT, were randomized to 
weekly intravenous infusions of 30 or 50 mg/kg/wk eteplirsen or placebo for 24 
weeks (n = 4/group). Placebo patients switched to 30 or 50 mg/kg eteplirsen 
(n=2/group) at week 25; treatment was open label thereafter. All patients had 
muscle biopsies at baseline and week 48. Efficacy included dystrophin-positive 
fibers and distance walked on the 6MWT.
RESULTS: At week 24, the 30 mg/kg eteplirsen patients were biopsied, and 
percentage of dystrophin-positive fibers was increased to 23% of normal; no 
increases were detected in placebo-treated patients (p≤0.002). Even greater 
increases occurred at week 48 (52% and 43% in the 30 and 50 mg/kg cohorts, 
respectively), suggesting that dystrophin increases with longer treatment. 
Restoration of functional dystrophin was confirmed by detection of sarcoglycans 
and neuronal nitric oxide synthase at the sarcolemma. Ambulation-evaluable 
eteplirsen-treated patients experienced a 67.3 m benefit compared to 
placebo/delayed patients (p≤0.001).
INTERPRETATION: Eteplirsen restored dystrophin in the 30 and 50 mg/kg/wk 
cohorts, and in subsequently treated, placebo-controlled subjects. Duration, 
more than dose, accounted for dystrophin production, also resulting in 
ambulation stability. No severe adverse events were encountered.