Comparison of ambulatory capacity and disease progression of Duchenne muscular dystrophy subjects enrolled in the drisapersen DMD114673 study with a matched natural history cohort of subjects on daily corticosteroids.
Duchenne muscular dystrophy is a rare genetic disorder with life-limiting pathology. Drisapersen induces exon 51 skipping, thereby producing a shorter but functional dystrophin protein. The longest available data are from an open-label extension study (PRO051-02) treating 12 boys with drisapersen (6 mg/kg/week subcutaneously). The median change (range) from baseline to week 177 in six-minute walking distance (6MWD) was 8 (-263, 163) metres. The current analysis aimed to put the results from PRO051-02 in the context of natural progression by comparing the functional trajectory of drisapersen-treated subjects to a matched natural history (NH) cohort, treated by standard of care. Subjects were matched individually by age and 6MWD, as the primary analysis, and by age and rise from floor (RFF), as sensitivity analysis. A total of 75 NH subjects were available for 6MWD analysis, of which matching was possible for 9 ambulant drisapersen-treated subjects. None of the 6 "stable" (baseline 6MWD ≥330 metres) drisapersen-treated subjects lost ambulation vs 4 out of 10 matched NH subjects over a comparable timeframe (~3.4 years), compared with 2 out of 3 ambulant "in decline" drisapersen-treated subjects vs all 6 matched NH subjects. A total of 79 NH subjects were available for RFF analysis. For continuous ambulatory subjects (N = 4), the RFF decline was more pronounced in the NH cohort than in the drisapersen-treated subjects. In conclusion, a comparison of ambulant drisapersen-treated subjects with matched NH subjects showed a difference in functional trajectories over a timeframe of up to 3.4 years in favour of drisapersen.
Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium. Electronic address: nathalie.goemans@uzleuven.be.
Nathalie
N
Goemans
The Queen Silvia Children's Hospital, Gothenburg, Sweden.
Mar
M
Tulinius
The Queen Silvia Children's Hospital, Gothenburg, Sweden.
Anna-Karin
AK
Kroksmark
Spica Consultants Ltd, Marlborough, United Kingdom.
Rosamund
R
Wilson
Department of Paediatrics and Child Neurology, University Hospitals Leuven, Leuven, Belgium.
Marleen
M
van den Hauwe
BioMarin Nederland BV, The Netherlands.
Giles
G
Campion
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005080:Exercise Test; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D016138:Walking
D000305:Adrenal Cortex Hormones; D009841:Oligonucleotides; C525434:PRO051
Antisense oligonucleotide; Comparative study; Drug therapy; Duchenne muscular dystrophy; Dystrophin synthesis; Exercise test