G.O.24: Eteplirsen in Duchenne Muscular Dystrophy (DMD): 3year update on Six-Minute Walk Test (6MWT) and Safety

DMD, a rare, degenerative, genetic disease that results in progressive muscle loss and premature death affects 1:5000 male births. It is caused by deletions in the dystrophin gene, which prevents production of the dystrophin protein. There are no approved treatments available, although corticosteroids have shown some benefit. Eteplirsen is an investigational drug designed to enable functional dystrophin production in boys who are amenable to skipping exon 51. Twelve boys aged 7–13years with eligible genotypes were randomized 1:1:1 to eteplirsen 30mg/kg/wk, 50mg/kg/wk, or placebo IV for 24-weeks. All patients transitioned into an ongoing open-label extension with 30 or 50mg/kg eteplirsen. Clinical efficacy endpoints included the 6-min walk test (6MWT) and pulmonary function testing. Safety assessments included adverse event recording, EKG, ECHO, hematology, blood chemistry and urinalysis. After 120weeks of treatment, a significant clinical benefit of 65m was observed (p=0.006) on the 6MWT for ambulatory-evaluable patients in the combined eteplirsen-treated cohorts (n=6) versus the placebo/delayed-treatment cohort (n=4). The eteplirsen-treated cohorts showed a decline of less than 14m in walking ability from baseline, which was not statistically significant. After a substantial decline in the first 36weeks of the study, the placebo/delayed-treatment cohort demonstrated stabilization in walking ability at week 48, i.e., 12weeks after initiation of treatment with eteplirsen when meaningful levels of dystrophin were likely produced, with <10m decline through 120weeks. No deaths, discontinuations due to AEs, treatment-related SAEs, or clinically significant abnormal laboratory, ECG, or ECHO findings were reported. Eteplirsen demonstrated a significant clinical benefit on the 6MWT over 120weeks, was well tolerated, and exhibited an unremarkable safety profile. Week 144 data will be presented.