Background: Duchenne muscular dystrophy (DMD) is a rare disease caused by DMD gene mutations resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, was shown via western blot to significantly increase dystrophin levels in DMD patients. Presented here are completed study results of >4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]) matched for age, glucocorticoid use, geographic location, and ambulatory ability.
Objectives: This trial (NCT03167255) is the extension of a published 24-week trial (NCT02740972) that examined dystrophin levels, timed function tests compared to CINRG DNHS, and safety in boys 4 to <10 years (N=16) treated with viltolarsen. Results: All 16 participants enrolled in this long-term trial (up to Week 216) to continue evaluation of motor function and safety. Both patients treated with viltolarsen and those in the CINRG DNHS control group received glucocorticoid treatment. Time to stand from supine, the primary efficacy endpoint, and secondary endpoints of time to run/walk 10 meters and time to climb 4 stairs (velocity) showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years for viltolarsen-treated participants compared with the CINRG DNHS control group, which declined over this same time period (statistically significant differences for multiple timepoints). Adverse events were mild. There were no treatment-related serious adverse events and no discontinuations. Conclusions: The study outcome of better motor function vs historical controls, and favorable safety profile, are demonstrated in this longest exon 53 skipping therapy trial to date. Viltolarsen can be considered an important part of the treatment strategy for DMD patients amenable to exon 53 skipping therapy.