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Neuromuscul Disord. 2014 Jan;24(1):16-24. doi: 10.1016/j.nmd.2013.09.004. Epub 2013 Sep 11.

Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial.

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Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, United States.
Institut de Myologie, Université Pierre et Marie Curie Paris 6, UM 76, INSERM U 974, CNRS UMR 7215, France.
GlaxoSmithKline, Research Triangle Park, NC, United States. Electronic address:
GlaxoSmithKline, Stockley Park, UK.
Prosensa Therapeutics BV, Leiden, The Netherlands.
GlaxoSmithKline, Stevenage, UK.
GlaxoSmithKline, London, UK.


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.


DMD; Drisapersen; Duchenne muscular dystrophy; Dystrophin; Exon 51; Non-ambulant; Oligonucleotide; Pharmacokinetics; Safety

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