PP09.16 – 2691: Eteplirsen, a phosphorodiamidate morpholino oligomer (PMO) for the treatment of Duchenne muscular dystrophy (DMD): 3.2 year update on six-minute walk test (6MWT), pulmonary function testing (PFT), and safety

Background/Objective DMD, a rare, degenerative, X-linked recessive genetic disease is mostly caused by frame-shift mutations in the dystrophin gene, preventing production of dystrophin protein. Eteplirsen, an investigational PMO designed to enable production of internally truncated yet functional dystrophin in boys amenable to exon 51-skipping, was evaluated in previously conducted clinical studies (33, 28, and 201), and is currently being evaluated in ongoing clinical trials. Methods Twelve eligible boys aged 7–13 years were randomized 1:1:1 to eteplirsen 30/50 mg/kg/wk, or placebo for 24 weeks. All patients transitioned into an ongoing open-label extension trial at Week 25 with eteplirsen 30/50 mg/kg. Efficacy endpoints included 6MWT, PFT, and %-dystrophin positive fibers. Safety assessments included AE recording, ECG, ECHO, and safety laboratory testing. Results After 3.2 years of treatment, all patients previously evaluable on 6MWT (mITT; n=10) showed continued ambulation. A 65.4 meter treatment benefit (p≤0.017) on 6MWT through Week 168 was observed for patients in the eteplirsen treated cohort (n=6) compared with the placebo/delayed-treatment cohort (n=4). After declining on average 7.6 meters/month baseline through Week 36, the placebo/delayed-treatment cohort experienced a decline of 2.2 meters/month and the eteplirsen cohort a decline of 1.9 meters/month in the timeframes in which meaningful levels of dystrophin were likely produced (Week 36–168 for the Placebo/delayed-treatment cohort and Week 12–168 for the eteplirsen cohort). All 12 patients demonstrated PFT stability baseline through Week 168, including MIP (+11.1%, p=NS), MEP (+13.5%, p=NS), and MIP/MEP %-predicted (-2.4%/-6.3%, p=NS). No deaths, discontinuations, treatment-related SAEs, immune activation including infusion reactions, or clinically significant abnormal laboratory, ECG, or ECHO findings were reported. Conclusion The observed slowed decline in walking distance and sustained pulmonary function contrasts with rapid declines in ambulation and pulmonary capacity observed in DMD natural history of boys this age. Eteplirsen was well tolerated after 3.2 years of weekly infusions.