1. In this randomized controlled trial, among the 121 patients with Duchenne muscular dystrophy (DMD) randomly assigned to a treatment group, vamorolone demonstrated loss of bone morbidities with no stunting of growth, compared with the prednisone and placebo groups.

2. Compared to placebo, the group assigned to vamorolone 6 mg/kg per day showed improvement by 6 weeks of treatment for patients with DMD, which was maintained up to 24 weeks of treatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness that can affect 1 in 3600 to 9300 male newborns. Treatment to delay the loss of ambulation typically consists of oral corticosteroids such as prednisone, however long-term use of corticosteroids can lead to negative side-effects such as stunting of growth and osteoporosis. Vamorolone is a structurally unique, dissociative steroidal anti-inflammatory drug that is capable of binding to the same target receptors as corticosteroids with a different mechanism of action. The objective of this study was to investigate whether vamorolone was able to retain efficacy while reducing safety concerns for patients with DMD. The 4 intervention arms of this randomized, double-blind, placebo-and prednisone-controlled 24-week trial included: placebo, prednisone, 0.75 mg/kg per day; vamorolone, 2 mg/kg per day; and vamorolone, 6 mg/kg per day. The primary efficacy endpoint was mean change from baseline to week 24 for time to stand from supine (TTSTAND) velocity in the vamorolone 6mg/kg per day group, vs placebo. A total of 121 boys were randomly assigned to treatment groups. The trial demonstrated that vamorolone was associated with loss of bone morbidities compared with prednisone, with no stunting of growth and no deleterious changes in bone biomarkers. Although limitations to this study were the relatively short study period of 24 weeks and small sample size, a strength was that the trial demonstrated the proven efficacy of vamorolone over a broad dose range (2 to 6 mg/kg per day).

Click to read the study in JAMA Neurology

Relevant Reading: Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment

In-Depth [randomized controlled trial]: This study was a randomized, double-blind, placebo-and prednisone-controlled 24-week clinical trial conducted between June 2018 to February 2021. A total of 133 boys with DMD (mean [SD] age, 5.4 [0.9] years) were screened. The primary outcome was time to stand from supine velocity (TTSTAND) in the vamorolone, 6mg/kg per day group vs placebo; secondary outcomes included TTSTAND velocity [vamorolone 2 mg/kg per day], 6-minute walk distance, time to run/walk 10m [vamorolone, 2 and 6 mg/kg per day]. This trial included two 24-week treatment periods. In the first treatment period of the trial, 121 participants were randomly assigned to either the placebo, prednisone (0.75mg/kg per day), vamorolone (2mg/kg per day), and vamorolone (6mg/kg per day), in a 1:1:1:1 ratio. In the second treatment period, participants in the placebo and prednisone groups crossed over to receive vamorolone treatment (either 2 or 6 mg/kg per day). The primary endpoint of change from baseline to week 24 for TTSTAND velocity for vamorolone, 6mg/kg per day, vs placebo was met (LSM [SE] velocity, 0.05 [0.01] m/s vs -0.01 [0.01] m/s; LSM difference, 0.06 m/s; 95% CI, 0.02-0.10 m/s; P=.002). While the placebo group showed a slight decline relative to baseline, the vamorolone 6 mg/kg per day group vs placebo showed improvement by 6 weeks of treatment (LSM [SE] velocity, 0.03 [0.01] m/s vs 0 [0.01] m/s; LSM difference, 0.03 m/s; 95% CI, 0.01-0.06 m/s; P=.02), with continued improvement to 12 weeks of treatment (LSM [SE] velocity, 0.04 [0.01] m/s vs -0.01 [0.01] m/s; LSM difference, 0.02 m/s; 95% CI, 0.02-0.08 m/s; P=.001), and was maintained up to 24 weeks of treatment. The secondary endpoint of change from baseline to week 24 for TTSTAND velocity for vamorolone, 2 mg/kg per day, vs placebo, was met (LSM [SE] velocity, 0.03 [0.01] m/s vs -0.01 [0.01] m/s; LSM difference, 0.05 m/s; 95% CI, 0.01-0.08 m/s; P=0.2).

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