Association of

Background and Objectives: Duchenne muscular dystrophy (DMD) is caused by pathogenic variants of the Methods: We analyzed 186 vamorolone trial participants with DMD (VBP15-002/003; VBP15-004) who were 4 to <7 years old and steroid-naïve at baseline. We stratified participants into gene variant classes by either variant location in the gene affecting different gene promoters (5' [Dp427-only] vs 3' [Dp427+other isoforms]) or residual dystrophin levels (null vs possible non-null [5' gene variants, exon 44 skippable, splice site]). We evaluated associations with baseline motor outcomes and treatment response (prednisone and vamorolone). Results: Participants with variants in ex63 and downstream (null for Dp427+Dp140+Dp71 protein isoforms) showed poorer baseline motor outcomes for time to stand from supine velocity than those with variants in ex1-44 (Dp427 only). No significant baseline differences were found between likely null and possible non-null variants. Participants with only Dp427 involvement showed significantly better treatment response for the 6-minute walk distance. Most of the comparisons of baseline motor function and treatment response were similar between variant classes. Discussion: The large variation in baseline motor function in young, steroid-naïve patients with DMD is only minimally explained by different gene variant classes. While there is strong literature support for 3' variants leading to a more severe motor and cognitive DMD phenotype, we found this variant class under-represented in our clinical trials. This suggests that they may fail inclusion criteria (failure to follow commands; poor motor function). Subgroup analyses in DMD clinical trials at a young age range based on gene variant class may not reveal significant differences and would be relatively noninformative.