Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular 
disorder caused by the absence of dystrophin protein due to mutations of the 
dystrophin gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide 
designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of 
the mRNA. This study assessed safety, tolerability, and pharmacokinetics of 
drisapersen after a single subcutaneous administration in non-ambulatory 
subjects. Eligible subjects were non-ambulant boys aged ⩾9years, in wheelchairs 
for ⩾1 to ⩽4years, with a diagnosis of DMD resulting from a mutation correctable 
by drisapersen treatment. Four dose cohorts were planned (3, 6, 9 and 12mg/kg), 
but study objectives were met with the 9mg/kg dose. Less than proportional 
increase in exposure was demonstrated over the 3-9mg/kg dose range, though post 
hoc analysis showed dose proportionality was more feasible over the 3-6mg/kg 
range. Single doses of drisapersen at 3 and 6mg/kg did not result in significant 
safety or tolerability concerns; however, at the 9mg/kg dose, pyrexia and 
transient elevations in inflammatory parameters were seen. The maximum tolerated 
dose of 6mg/kg drisapersen was identified for further characterization in 
multiple dose studies in the non-ambulant DMD population.