Abstract Details

Title Drisapersen treatment for Duchenne muscular dystrophy: results of a 96-week follow-up of an open-label extension study following two placebo-controlled trials

Topic Child Neurology and Developmental Neurology

Presentation(s) (-)

Poster/Presentation
Number 001

Objective

Background DRIS is a 2’-O-methyl-phosphothioate oligonucleotide designed to skip exon 51 of dystrophin pre-mRNA in subjects with Duchenne muscular dystrophy (DMD). Two placebo-controlled trials showed a treatment benefit favoring DRIS on 6-minute walk distance (6MWD) after 48 weeks’ treatment (DMD114044, 10.3 meters; DMD114117, 35 meters). DMD114349 was an open-label extension of these studies.

Design/Methods Subjects with DMD (>=5 years; ambulant; steroid-treated; rise from floor <=7 sec [DMD114117 only]; dystrophin mutation correctable by exon-51 skipping) who completed the feeder studies were eligible. Safety (datacut June 2013) and efficacy (datacut October 2013) data are reported.

Results Safety analysis (n=186) demonstrated that injection-site reactions, renal events, and thrombocytopenia were the most prominent findings. At 48 weeks of DMD114349, subjects who received DRIS (n=69) showed a clinically meaningful difference in 6MWD compared with those in the placebo/delayed-treatment arm (n=44; mean [95% CI] change, –66.8 [–96.6, –36.9] and –112.9 [–152.0, –73.8] meters for a total of 96 and 48 weeks of DRIS, respectively; mean difference, +46 meters). Subjects enrolled in DMD114044 had a 49-meter difference between DRIS (n=52) and placebo/delayed treatment (n=31) from original baseline. Those from DMD114117 had a 52-meter difference from original baseline between DRIS (n=17) and placebo/delayed treatment (n=13) in favor of DRIS; decline was only 5 meters in the DRIS arm.

Conclusions The long-term safety of DRIS appears similar to previous clinical trials, except for the occurrence of thrombocytopenia. A total of 96 weeks of DRIS treatment resulted in a clinically meaningful difference from placebo/delayed DRIS of 46 meters. This extension study suggests maintenance of benefit in a feeder study population with less severe disease, and a clinically meaningful benefit slower to emerge in a feeder study population that is, on average, more severely affected.

Authors/Disclosures
Nathalie M. Goemans, MD (University Hospitals Leuven)	Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Goemans has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Goemans has received publishing royalties from a publication relating to health care.
	No disclosure on file
Craig McDonald, MD (UC Davis Dept. of PM&R)	Dr. McDonald has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH.
Carolyn B. Watson (Glaxo Wellcome)	No disclosure on file
Maciej M. Mrugala, MD, PhD, MPH, FAAN (Mayo Clinic)	Dr. Mrugala has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Veevo Biomedicines Inc. Dr. Mrugala has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arbor Pharmaceuticals. Dr. Mrugala has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra-Zeneca. Dr. Mrugala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Mrugala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyiatec . The institution of Dr. Mrugala has received research support from Arbor Pharmaceuticals. Dr. Mrugala has a non-compensated relationship as a Program Director with Society for Neuro-Oncology that is relevant to AAN interests or activities.
John E. Kraus, MD, PhD (GlaxoSmithKline)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Giles Campion, MD, PhD	No disclosure on file

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