Paula R. Clemens, Anders Berglund, Marianela Schiava, Meredith K. James, Michael P. McDermott, Katherine Bushby, Erik Lampa, Edward Thomas James Rochford, Leanne M. Ward, Robert C. Griggs, Eric P. Hoffman, Michela Guglieri
BACKGROUND AND OBJECTIVES: Vamorolone demonstrated similar efficacy for Duchenne muscular dystrophy (DMD) compared with prednisone in a 24-week exploratory analysis and may reduce key side effects compared with classic corticosteroids. In this study, we compare the efficacy and anthropometric effect of vamorolone 6 mg/kg/d with prednisone 0.75 mg/kg/d and deflazacort 0.9 mg/kg/d in steroid-naïve boys aged 4 to <7 years using data from 2 trials. METHODS: VISION-DMD was a phase 2b, 48-week randomized, double-blind trial assessing vamorolone 2 and 6 mg/kg/d vs placebo and prednisone 0.75 mg/kg/d to 24 weeks. Finding the Optimum Steroid Regimen for DMD (FOR-DMD) was a double-blind, parallel-group randomized trial comparing daily prednisone 0.75 mg/kg/d, daily deflazacort 0.9 mg/kg/d, and intermittent prednisone 0.75 mg/kg (10/10 days on/off). Entropy balancing generated weighted data for mixed model for repeated measures analyses that compared VISION-DMD vamorolone 6 mg/kg/d efficacy and anthropometric outcomes with FOR-DMD prednisone and deflazacort outcomes at 6 and 12 months. Inclusion criteria were boys with genetically confirmed DMD, age 4 to <7 years, ambulatory, and able to complete a time-to-stand (TTSTAND) assessment in <10 seconds at baseline. RESULTS: -scores [95% CI]: vamorolone vs prednisone 0.57 [0.24-0.90]; vamorolone vs deflazacort 0.72 [0.53-0.91]). DISCUSSION: Vamorolone demonstrated numerically similar TTSTAND velocity changes to prednisone and deflazacort at 1 year; however, interpretations of differences are limited by 95% CIs crossing minimally important difference thresholds. Further evidence of the growth-protective effect of vamorolone was observed; however, all treatments increased BMI. Vamorolone provides a linear growth-protective classic corticosteroid alternative. TRIAL REGISTRATION INFORMATION: NCT03439670; NCT01603407. CLASSIFICATION OF EVIDENCE: This Class III study did not definitively identify differences in efficacy between vamorolone and classic corticosteroids but found that vamorolone protects linear growth in boys with DMD.