Impact of vamorolone, prednisone and placebo on linear growth in the VISION-DMD (VBP15-004) study, as measured by changes in height over 6 months


Clinical Trials

Poster Number: M190


Ana de Vera, MD, Santhera Pharmaceuticals, Wido Tilmann, Aki Linden, Raoul Rooman, MD, Santhera Pharmaceuticals, Eric Hoffman, PhD, AGADA Biosciences, Inc., Paula Clemens, MD, University of Pittsburgh, Michela Guglieri, Newcastle University and Newcastle Hospitals NHS Foundation Trust, VBP1-004 investigators

Background: Corticosteroids are recommended as standard of care for patients with Duchenne muscular dystrophy (DMD). However, children with DMD are on average shorter than the general population by the age of 5 years, and daily dosing with prednisone or deflazacort leads to further stunting of growth (Bello et al. 2015 PMID: 26311750; Stimpson et al. 2022 PMID: 35073949). In the Phase 2b VISION-DMD study (NCT03439670) height percentile (adjusted by age using US CDC growth charts) was shown to decline from baseline to month 6 in patients treated with prednisone, but not in those treated with the dissociative corticosteroid vamorolone at 6 mg/kg/day (Guglieri et al. 2022 PMID: 36036925).

Objective: To further study the impact of vamorolone or prednisone vs placebo on linear growth in the VISION-DMD study by reporting unadjusted changes in height (cm) and patient-level changes in height over the course of 6 months.

Methods: The design of the VISION-DMD study has been reported previously. Boys aged 4 to <7 years were randomised to placebo, prednisone 0.75 mg/kg/day, vamorolone 2 mg/kg/day or vamorolone 6 mg/kg/day. Height was recorded at baseline and at 12-week intervals. This analysis included 118 participants in the safety population. Results: At baseline, median height ranged from 106 to 111 cm across the treatment groups. After 6 months of treatment, median height increases were lower in the prednisone group (n=30, 2.60 cm) than in the placebo group (n=28, 3.55 cm, p=0.03) or vamorolone 6 mg/kg/day group (n=26, 3.50 cm, p=0.009). There were no significant differences in median height increase between either vamorolone group and placebo (p>0.1). In the prednisone group, 30.0% of children showed reductions in height z-score ≥0.2 standard deviations after 6 months, compared with 18.5% in the vamorolone 2 mg/kg/day group, 10.7% in the placebo group and 0 children in the vamorolone 6 mg/kg/day group.

Conclusion: In patients with DMD aged 4 to <7 years, absolute height (cm) values after 6 months of treatment showed similar increases with vamorolone and placebo, while significantly less growth (i.e. growth stunting) was observed with prednisone.