Vamorolone may be safer alternative to prednisone in boys with Duchenne muscular dystrophy
Click Here to Manage Email Alerts
Vamorolone demonstrated efficacy and safety in the treatment of boys with Duchenne muscular dystrophy over a 24-week treatment period and may be safer than prednisone, according to a study published in JAMA Neurology.
“Vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug that binds to the same target receptors as the corticosteroid class (glucocorticoid receptor, mineralocorticoid receptor), but shows a distinct chemical structure and differences in mechanism of action,” Michela Guglieri, MD, of the John Walton Muscular Dystrophy Research Center at Newcastle University in the United Kingdom, and colleagues wrote.
The researchers aimed to determine whether vamorolone maintains effectiveness while reducing safety concerns with use in children diagnosed with Duchenne muscular dystrophy (DMD).
They initiated a double-blind, placebo- and prednisone-controlled 24-week clinical trial from June 2018 to February 2021, with 24 weeks of follow-up. The study was conducted at 33 referral centers in 11 countries and included 133 boys, aged 4 to 7 years, with genetically confirmed DMD who were not previously treated with corticosteroids.
Participants were split into four groups — placebo; prednisone at 0.75 mg/kg per day; vamorolone at 2 mg/kg per day; and vamorolone at 6 mg/kg per day. Outcomes of interest were efficacy, including motor function (primary — time to stand from supine velocity in the vamorolone 6 mg/kg per day group compared with placebo; secondary — time to stand from supine velocity [vamorolone 2 mg/kg per day], 6-minute walk distance, time to run/walk 10 meters [vamorolone 2 and 6 mg/kg per day]; exploratory — NorthStar Ambulatory Assessment, time to climb 4 stairs; and safety, which included growth, bone biomarkers and a corticotropin (ACTH)-challenge test.
Results showed that 121 participants were randomly assigned to treatment groups, and 114 completed the full treatment period. The primary outcome for change from baseline to week 24 time was met for stand velocity for vamorolone 6 mg/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m/s compared with placebo 0.01 [0.01] m/s; 95% CI, 0.02-0.10) and the first four secondary outcomes — time to stand velocity, vamorolone 2 mg/kg per day compared with placebo; 6-minute walk test, vamorolone, 6 mg/kg per day compared with placebo; 6-minute walk test, vamorolone 2 mg/kg per day, compared with placebo; and time to run/walk 10 meters velocity vamorolone 6 mg/kg per day compared with placebo.
Researchers further reported that height percentile declined in prednisone-treated (not vamorolone-treated) participants (change from baseline: prednisone, 1.88 percentile compared with vamorolone 6 mg/kg per day, +3.86 percentile).
In addition, bone turnover markers declined with prednisone but not with vamorolone. Participants with DMD at baseline demonstrated low ACTH-stimulated cortisol and high incidence of adrenal insufficiency.
“The proven efficacy over a broad dose range may enable physicians to adjust dose based on clinical observations and patient preferences,” Guglieri and colleagues wrote.