Data from: Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Objective: We carried out first-in-patient studies of vamorolone, a
first-in-class dissociative steroidal anti-inflammatory drug, in Duchenne
muscular dystrophy. Methods: An open-label, multiple-ascending dose study
of vamorolone was conducted in 48 boys with Duchenne muscular dystrophy (4
to <7 years, steroid-naïve). Dose levels were 0.25, 0.75, 2.0 and
6.0 mg/kg/day using an oral suspension formulation (12 boys/dose level;
1/3rd to 10x glucocorticoid dose in DMD). Results: Over a 24-week
treatment period, oral administration of vamorolone at all doses tested
was safe and well-tolerated. The 2.0 mg/kg/day dose group met the primary
efficacy outcome of improved muscle function (time to stand; 24 weeks
vamorolone treatment versus natural history controls), without evidence of
most adverse effects of glucocorticoids. Significant dose-responsive
improvements in 10 meter run/walk, and six-minute walk test were observed
for 2.0 and 6.0 mg/kg/day dose groups. The morbidity of most concern to
many chronic glucocorticoid users, bone loss, was not seen with vamorolone
at any dose, as evidenced by serum osteocalcin. Biomarker outcomes for
adrenal suppression and insulin resistance were also less impacted in
vamorolone-treated DMD patients, relative to published studies of
glucocorticoid therapy. Conclusions: Vamorolone demonstrated both efficacy
and a reduction in adverse effects in DMD patients compared to traditional
glucocorticoids in a 24-week, open-label study. Vamorolone has potential
to replace chronic glucocorticoids in many disorders where side effects
detract from patient quality of life. Classification of Evidence: This
study provides Class II evidence that certain dosages of vamorolone are
well tolerated and effective in improving muscle function in DMD.