Vamorolone Shows Dose Related Improvement in Young Patients With Duchene Muscular Dystrophy

Daily vamorolone treatment for Duchenne muscular dystrophy suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study.

Vamorolone, a novel dissociative steroidal anti-inflammatory drug, was found to be effective, safe, and well tolerated in children with Duchenne muscular dystrophy (DMD), according to study results published in Neurology.

Previous studies have shown an improved safety profile of vamorolone compared with glucocorticoid, which is the current standard of care for DMD. The current study (VBP15-003; identifier: NCT02760277), which sought to assess the efficacy of vamorolone, is a 24-week extension study of a previous phase 2a study (VBP15-002; identifier: NCT02760264) that assessed the pharmacokinetics and safety of vamorolone in children with DMD.

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The primary goal of the study was to define optimal doses of vamorolone, and 4 doses were evaluated: 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation. Each dose group included 12 patients who were monitored for safety in the first trial (VBP15-002) and were subsequently enrolled in a 24-week extension phase at the same dose (VBP15-003).

The open-label, multiple-ascending-dose clinical trial included 48 glucocorticoid-naive boys with DMD (ages 4-7 years, mean age 4.9±0.9 years). All the doses of vamorolone were found to be safe and well tolerated over the 24-week treatment period.

The efficacy of the treatment was assessed by time to stand from supine velocity (rises per second) change from VBP15-002 baseline to VBP15-003 week 24 for the vamorolone group compared with the untreated control group. The mean difference in change from baseline to week 24 was significant for comparison of the 2.0-mg/kg/d group with the untreated controls (P =.04). The mean difference in change from baseline to week 24 was also significant for the comparison of the 2.0-mg/kg/d and 6.0-mg/kg/d groups with the 0.25-mg/kg/d group (P =.02 and P =.04, respectively).

The 2.0-mg/kg/d dose showed superior clinical safety to prednisone treatment with less weight gain and improvement of bone turnover and insulin resistance biomarkers. There was evidence of adrenal suppression in a subset of boys treated with 2.0 mg/kg/d vamorolone based on reduced morning cortisol levels.

The highest dose of vamorolone tested, 6.0 mg/kg/d, showed greater improvements in 6-minute walk test and time to run/walk 10 meters. However, this dose also showed more safety concerns than the 2.0-mg/kg/d dose, with weight gain similar to that with prednisone, increased incidence of adrenal suppression, and mild increases of serum insulin, which might indicate increased insulin resistance.

The researchers acknowledged several study limitations, including the open-label, nonrandomized, non-placebo-controlled design, and data limited to children aged 4 to 7 years.

“This study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated,” concluded the researchers.

A double blind, placebo-controlled clinical trial of vamorolone is currently underway (VBP15-004; identifier: NCT03439670), which will test 2 doses of vamorolone (2.0 and 6.0 mg/kg/d) vs placebo and prednisone (0.75 mg/kg/d). The study is enrolling 120 patients (30 per arm) with the same inclusion criteria as the exploratory dose-ranging study described here.

Disclosure: This clinical trial was supported by ReveraGen BioPharma. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Hoffman EP, Schwartz BD, Mengle-Gaw LJ, et al; Cooperative International Neuromuscular Research Group. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology. 2019;93(13):e1312-e1323.