BACKGROUND: Duchenne muscular dystrophy is caused by dystrophin deficiency and 
muscle deterioration and preferentially affects boys. 
Antisense-oligonucleotide-induced exon skipping allows synthesis of partially 
functional dystrophin. We investigated the efficacy and safety of drisapersen, a 
2'-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks.
METHODS: In this exploratory, double-blind, placebo-controlled study we 
recruited male patients (≥5 years of age; time to rise from floor ≤7 s) with 
Duchenne muscular dystrophy from 13 specialist centres in nine countries between 
Sept 1, 2010, and Sept 12, 2012. By use of a computer-generated randomisation 
sequence, we randomly allocated patients (2:2:1:1; block size of six; no 
stratification) to drisapersen 6 mg/kg or placebo, each given subcutaneously and 
either continuously (once weekly) or intermittently (nine doses over 10 weeks). 
The primary endpoint was change in 6-min walk distance (6MWD) at week 25 in 
patients in the intention-to-treat population for whom data were available. 
Safety assessments included renal, hepatic, and haematological monitoring and 
recording of adverse events. This trial is registered with ClinicalTrials.gov, 
number NCT01153932.
FINDINGS: We recruited 53 patients: 18 were given continuous drisapersen, 17 
were given intermittent drisapersen, and 18 were given placebo (continuous and 
intermittent groups combined). At week 25, mean 6MWD had increased by 31·5 m (SE 
9·8) from baseline for continuous drisapersen, with a mean difference in change 
from baseline of 35·09 m (95% CI 7·59 to 62·60; p=0·014) versus placebo. We 
recorded no difference in 6MWD changes from baseline between intermittent 
drisapersen (mean change -0·1 [SE 10·3]) and placebo (mean difference 3·51 m 
[-24·34 to 31·35]) at week 25. The most common adverse events in 
drisapersen-treated patients were injection-site reactions (14 patients given 
continuous drisapersen, 15 patients given intermittent drisapersen, and six 
given placebo) and renal events (13 for continuous drisapersen, 12 for 
intermittent drisapersen, and seven for placebo), most of which were subclinical 
proteinuria. None of the serious adverse events reported (one for continuous, 
two for intermittent, and two for placebo) resulted in withdrawal from the 
study.
INTERPRETATION: Continuous drisapersen resulted in some benefit in 6MWD versus 
placebo at week 25. The safety findings are similar to those from previous 
studies. Ambulation improvements in this young population with early-stage 
Duchenne muscular dystrophy are encouraging but need to be confirmed in larger 
studies.
FUNDING: GlaxoSmithKline, Prosensa Therapeutics BV (a subsidiary of Prosensa 
Holding NV).