Background: Vamorolone is a dissociative steroidal anti-inflammatory that seeks to retain efficacy and reduce safety concerns compared to corticosteroids via changes to structure/activity relationships with the glucocorticoid receptor. An open label study in Duchenne muscular dystrophy (DMD) suggested a favorable efficacy-safety profile, which was recently confirmed in a double blinded, prednisone- and place-controlled 48-week vamorolone trial with crossover (VBP15-004).
Objective: To present delayed start analysis of efficacy outcomes from VBP15-004.
Methods: Steroid-naïve boys with DMD (5.4±0.9 years; n=121) randomized to placebo for 24 weeks (Period 1) crossed-over to two vamorolone groups (2.0 or 6.0 mg/kg/day) for Period 2. An ancillary SAP pre-specified comparison of timed function test velocities (stand [TTSTANDV], climb [TTCLIMBV], and run/walk 10m [TTRWV], six-minute walk distance, and NSAA data from participants initially assigned to placebo (delayed-starters) vs. those assigned and retained on vamorolone throughout (early-starters). Change was modeled at weeks 12, 24, 40, and 48 using mixed models for repeated measures for early-starters (vamorolone 2.0 mg/kg/day [n=30]; vamorolone 6.0 mg/kg/day [n=28]) and delayed-starters (placebo->vamorolone 2.0 mg/kg/day [n=14]; placebo->vamorolone 6.0 mg/kg/day [n=14]).
Results: There was an improvement in multiple efficacy outcomes in delayed starters post-crossover to vamorolone after 24 weeks (e.g., TTSTANDV week 48 vs week 24; p < 0.05). Early-starters (vamorolone 6.0 mg/kg/day) had increased outcome means compared with delayed-starters (placebo->vamorolone 6.0 mg/kg/day) for all 5 outcomes at all timepoints with 1 exception (TTRWV at week 48). At 48 weeks, only the mean for TTCLIMBV was statistically significant between early- and delayed-starters (p<0.05). Other comparisons (e.g., vamorolone 2.0 mg/kg/day throughout vs. placebo->vamorolone 2.0 mg/kg/day or pooled dose groups) yielded similar findings for the most part.
Conclusions: A delayed start analysis of early-starters vs. delayed-starters showed that the initial disease-modifying effect of vamorolone with early initiation was maintained over follow-up period (although not always statistically significant). This global assessment of efficacy is supportive of the efficacy profile of vamorolone.