Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial

Clinical Snapshot

Key Findings

• P Value: Not reported for primary comparisons

• Effect Size: Vamorolone vs prednisone: 0.004 rises/second difference; vamorolone vs deflazacort: 0.001 rises/second difference

• Primary Outcome: TTSTAND velocity changes at 12 months showed similar improvements across all treatments

• Nnt Or Sensitivity: Minimal clinically important difference threshold: 0.023 rises per second (confidence intervals cross this threshold)

• Confidence Interval: Vamorolone vs prednisone: -0.025 to 0.032; vamorolone vs deflazacort: -0.027 to 0.028

Clinical Application

Vamorolone not currently available in Australia; would require TGA approval and PBS listing for practical implementation Aligns with RACGP and specialist guidelines recommending early corticosteroid therapy for DMD; growth preservation particularly relevant given long-term treatment requirements Steroid-naïve boys with DMD aged 4-7 years in Australian paediatric neurology and rehabilitation services

Abstract

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: All interventions showed motor improvements relative to baseline at 6 and 12 months. Using the weighted cohorts and at 12 months, vamorolone 6 mg/kg/d (n = 28) had similar changes in TTSTAND velocity, the primary motor endpoint component in both trials, vs daily prednisone (n = 50) or deflazacort (n = 55; mean baseline age 5.42 years all groups), but with CIs overlapping minimal clinically important thresholds of 0.023 rises per second (TTSTAND velocity least squares mean [LSM] difference [95% CI]: vamorolone 6 mg/kg/d vs prednisone 0.75 mg/kg/d, 0.004 rises per second [-0.025 to 0.032] and vs deflazacort 0.9 mg/kg/d, 0.001 rises per second [-0.027 to 0.028]). Body mass index (BMI) Z-scores increased in all groups, greatest with vamorolone (12-month LSM difference [95% CI]: vamorolone vs prednisone 0.57 [0.24-0.90]; vamorolone vs deflazacort 0.29 [0.03-0.56]), whereas growth slowdown occurred in prednisone- and deflazacort-treated boys but not vamorolone (12-month LSM difference in height Z-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.

References

1. 1.Clemens, P. R., Berglund, A., Schiava, M., James, M. K., McDermott, M. P., Bushby, K., Lampa, E., Rochford, E. T. J., Ward, L. M., Griggs, R. C., Hoffman, E. P., & Guglieri, M. (2026). Vamorolone for Duchenne Muscular Dystrophy: A Cross-Trial Efficacy Comparison With Classic Corticosteroids From the FOR-DMD Trial. Neurology. https://doi.org/10.1212/WNL.0000000000214756