K. Berry

Longitudinal effect of eteplirsen vs. historical control on ambulation in DMD

To continue evaluation of the long‐term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three‐year progression of eteplirsen‐treated patients was compared to matched historical controls (HC).

C-2. Eteplirsen, a Phosphorodiamidate Morpholino Oligomer (PMO) for the Treatment of Duchenne Muscular Dystrophy (DMD): 168 Week Update on Six-Minute Walk Test (6MWT), Pulmonary Function Testing (PFT), and Safety

DMD is a rare, degenerative, X-linked recessive genetic disease that results in progressive muscle loss and premature death. DMD is caused by mutations in the dystrophin gene that lead to a reading frame shift and premature translation termination. Exon skipping, a promising disease-modifying approach for DMD, can be induced by eteplirsen, a charge neutral PMO that selectively binds to exon 51 of dystrophin pre-mRNA, restoring the open reading frame and enabling production of an internally truncated yet functional dystrophin protein as found in the less severe dystrophinopathy, Becker muscular dystrophy (BMD).

S.P.3 Diverse walking distances predict functional outcomes in Duchenne Muscular Dystrophy

Evaluate the utility of timed walking tests in DMD. Many different timed walking tests have been shown to be accurate, reproducible, and simple to administer (10 m walk (10 mw), 2 min (2MWT), and 6 min (6MWT)). Recently the 6MWT has emerged as the gold standard for use in clinical trials. Thirty five subjects with DMD were evaluated 95 times. Tests include walking distance; isometric quadriceps strength testing and the North Star Ambulatory Assessment (NSAA). Mixed model analysis revealed that both the 2MWT and 6MWT are highly significant correlations to the NSAA (p < 0.0001) and quadriceps strength (p = 0.05). Boys walked a consistent speed throughout the entire test. Velocity during each minute of a single session ranged from 0.97 to 1.06 m/s, showing a high degree of correlation at each timed interval (r = 0.725 − 0.921; p < 0.001). Wilcoxon signed rank tests on walking test group data revealed no significant difference between distances on day 1 and day 2 for either the 2MWT (p = 0.8) or the 6MWT (p = 0.5). Individual variability between days, however, was quite large. For 6MWT distance walked between subsequent days ranged from 0–44 m or 0–59% (mean = 6.4% = /− 10.26) of the total distance. Variability for the 2MWT was similar, ranging from 0–33 m or 0–56% (mean = 7.9% = /−10.05). In DMD the 2MWT is comparable to the 6MWT. Both correlate with quadriceps strength and function. The caveat for the data set analyzed here is that each minute was part of a 6MWT. Future studies will need to test walking velocity in separate designated 6 and 2 min tests.