FP.27 Results of a double-blind cross-over trial of vamorolone in DMD: A safer alternative to corticosteroids

Abstract

Vamorolone is a dissociative steroidal anti-inflammatory drug that changes structure/activity relationships with the glucocorticoid receptor. Steroid-naïve boys with genetically confirmed DMD (5.4±0.9 years) were randomized (n=121) in a double-blind, placebo- and prednisone-controlled, Phase 2b (dose-finding) efficacy and safety trial of vamorolone. The trial was designed with a 24-week Period 1 with participants randomized to 4 groups (placebo, prednisone, vamorolone 2 mg/kg/day, vamorolone 6 mg/kg/day), and a 24-week Period 2 where the placebo and prednisone groups crossed over to one of the vamorolone dose groups. 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 mg/kg/day vs. placebo, 2 mg/kg/day vs. placebo; 6-minute walk test 6 mg/kg/day vs. placebo, 2 mg/kg/day vs. placebo; time to run/walk 10 meters velocity 6 vs. placebo). Height percentile declined in prednisone-treated, but not vamorolone-treated participants. Bone turnover markers declined with prednisone treatment but not vamorolone. Comparing the 2 vamorolone dose groups over a 48-week treatment period, vamorolone 6 mg/kg/day showed greater improvements in motor outcomes compared to 2 mg/kg/day for some outcomes (TTSTAND, 6MWT and TTCLIMB), but similar efficacy in others (NSAA, TTRW). Stunting of growth was not seen at either dose group over the 48-week treatment period, and body mass index stabilized after an initial increase during first 24 weeks. Prednisone-treated participants (Period 1) that crossed over to vamorolone showed maintenance of efficacy across all efficacy endpoints for vamorolone 6 mg/kg/day. Annualized rates of adverse events were reduced after the switch from prednisone to vamorolone (all events: 20% reduction, steroid-related events: 40% reduction). Stunting of growth observed with prednisone during Period 1 was reversed during treatment with vamorolone during Period 2. Placebo-treated participants in Period 1 that crossed over to vamorolone in Period 2 (delayed starters) showed an improvement in multiple efficacy outcomes after the switch to vamorolone. In summary, the trial showed compelling evidence of efficacy of vamorolone with improved safety compared to prednisone.