Vamorolone is a dissociative steroidal anti-inflammatory drug that seeks to retain efficacy and reduce safety concerns in patients with DMD compared to corticosteroids via changes to structure/activity relationships with the glucocorticoid receptor.
The objective of this analysis is to evaluate efficacy and safety of continuous 48-week vamorolone treatment.
VISION-DMD (VBP15-004) is a 48-week randomized, double-blind study consisting of two periods. During Period 1, 121 patients were randomized 1:1:1:1 to vamorolone 2 or 6 mg/kg/day, prednisone 0.75 mg/kg/day or placebo for 24 weeks. During Period 2, patients continued their initial vamorolone dose or crossed over to vamorolone 2 or 6 mg/kg/day. Changes from baseline to Week 48 in efficacy outcomes; time to stand velocity (TTSTANDV), 6-minute walk distance (6MWT), 10-meter run/walk velocity (TTRWV), NSAA score and 4-stair climb velocity (TTCLIMBV) were analyzed with MMRM.
Of the 121 patients, 56 received vamorolone during both Period 1 and 2. Two of 56 patients discontinued treatment during Period 2 (1 adverse event, 1 consent withdrawn). For vamorolone 6 mg/kg/day, efficacy was maintained or further improved from Week 24 to Week 48, whilst for vamorolone 2 mg/kg/day, efficacy was maintained in some efficacy endpoints but not all. Differences between dose levels were seen in TTSTAND (p=0.001), 6MWT (p=0.047) and TTCLIMB (p=0.031), while not in TTRW (p=0.375) or NSAA (p=0.602). Three serious adverse events were reported during the 48 weeks: perforated appendicitis (2 mg/kg/day), asthma (6 mg/kg/day) and viral gastroenteritis (6 mg/kg/day), all considered unrelated to vamorolone. Stunting of growth was not seen and body mass index stabilized after an initial increase during the first 24 weeks.
Efficacy of vamorolone 6 mg/kg was maintained throughout 48 weeks across all outcome measures, whilst only across some measures for 2mg/kg/day. Vamorolone treatment was generally well tolerated on both dose levels throughout 48 weeks.