Duchenne muscular dystrophy is an X-linked recessive neuromuscular disorder caused by loss of dystrophin in muscle tissues. Vamorolone is a dissociative steroidal anti-inflammatory drug that changes structure/activity relationships with the glucocorticoid receptor. Previous open label studies of vamorolone have suggested retention of efficacy with reduced safety concerns of corticosteroids.
Steroid-naïve boys with genetically confirmed DMD (5·4±0·9 years; n=121) were randomized in a double-blind, placebo- and prednisone-controlled, Phase 2b (dose-finding) efficacy and safety trial of vamorolone. The primary end point was time to stand from supine velocity (6·0 mg/kg/day vamorolone vs. placebo). Hierarchical testing was used for secondary end points (time to stand velocity, six-minute walk test, and time to run/walk 10 meters velocity at both 6·0 and 2·0 mg/kg/day dose groups).
Vamorolone-treated groups showed improvements in motor function tests over the 24-week treatment period. The trial met the primary and first four sequential secondary end points for change from baseline to Week 24 (time to stand velocity: vamorolone 6·0 mg/kg/day vs. placebo p=0·002, 2·0 mg/kg/day vs. placebo p=0·02; 6-minute walk test 6·0 mg/kg/day vs. placebo p=0·003, 2·0 mg/kg/day vs. placebo p=0.009; time to run/walk 10 meters velocity 6·0 vs. placebo p=0·002). Height percentile declined in prednisone-treated, but not vamorolone-treated participants (least square means [standard error] prednisone ?1·61%tile [1·41] vs. vamorolone 6·0 mg/kg/day +3·40%tile [1·55]; p=0·02). Bone turnover markers declined with prednisone treatment but not vamorolone (p<0·001 for all comparisons). All 3 treatment groups led to adrenal insufficiency, but vamorolone 2·0 mg/kg/day less than prednisone (p<0·002).
Vamorolone is an effective and safer alternative to corticosteroids in Duchenne muscular dystrophy.
(Funded by National Institutes of Health NINDS, and European Commission Horizons 2020; NCT03439670).