source: American Academy of Neurology
Edward Kaye, Jerry Mendell, Louise Rodino-Klapac, Zarife Sahenk, Kandice Roush, Loren Bird, Linda Lowes, Lindsay Alfano, Ana Maria Gomez Ramirez, Sarah Lewis, Vinod Malik, Kim Shontz, Christopher Shilling, Peter Sazani, Jihad Saoud
The objective of this study is to establish long-term efficacy of eteplirsen treatment, targeted to skip exon 51.
DMD is a rare, degenerative, genetic disease that results in progressive muscle loss and premature death. Affecting 1 in 5000 male births, DMD is caused by the inability to produce the dystrophin protein. There are no approved drugs available to treat DMD. Eteplirsen is an investigational therapy designed to enable functional dystrophin production in boys who are amenable to exon 51-skipping therapy (~13%).
Twelve boys aged 7-13 years with eligible genotypes were randomized 1:1:1 to 30 mg/kg, 50 mg/kg, or placebo. Upon completion of a 24-week double-blind, placebo-controlled study phase, all subjects were enrolled in an open-label extension and the placebo-treated subjects initiated eteplirsen treatment. The critical clinical endpoint was the change in 6-minute walk test (6MWT) distance from baseline compared to the placebo/delayed-treatment cohort.
After 96 weeks of treatment, a significant clinical benefit of 71 meters was observed (p<=0.001) on the 6MWT for ambulatory-evaluable subjects in the combined eteplirsen-treated cohorts (n=6) versus the placebo/delayed-treatment cohort (n=4). The eteplirsen-treated cohorts showed approximately 5% decline (19.3 meters) in walking ability from baseline. No clinically significant treatment-related adverse events were seen through 96 weeks.
Through 96 weeks of treatment, eteplirsen demonstrated a significant clinical benefit on the 6MWT with no clinically significant treatment-related adverse events. Data on these outcomes will be reported through 164 weeks of treatment.
Columbus Children's Research Columbus, USA; National Children's Hospital Columbus, USA; Sarepta Therapeutics Cambridge, USA; The Research Institute at Nationwide Children's Hospital Columbus, USA