Phase 1 and phase 2a studies suggest that the drug may have an improved safety profile. To assess possible efficacy and define optimal doses, the investigators conducted the 24-week extension study. Participants were boys aged 4 years to younger than 7 years who had never been treated with glucocorticoids. They received 0.25, 0.75, 2.0, or 6.0 mg/kg per day vamorolone in an oral suspension formulation. Twelve boys received each dose level.
“Vamorolone was well tolerated ... with no adverse events leading to reduction of drug dosing or withdrawal from the trial,” they said. “The [timed stand from supine] primary outcome measure in vamorolone-treated patients with DMD supports efficacy of the 2.0-mg/kg/d dose ... at 24 weeks,” they said. A secondary outcome measure, the 6-minute walk test, supports efficacy at this dose at 12 and 24 weeks of treatment.
Furthermore, the data indicate that the 2.0-mg/kg per day dose may be associated with less weight gain and improved bone turnover and insulin resistance biomarkers, relative to prednisone therapy. “There was evidence of adrenal suppression in a subset of boys with DMD treated with 2.0 mg/kg/d vamorolone, with 18% of patients showing reduced morning cortisol levels,” the authors said. “Future studies of vamorolone will include adrenocorticotropic hormone–challenge tests to further explore adrenal function.”
A double-blind, placebo-controlled trial of vamorolone is underway. Investigators are testing two doses of vamorolone (2.0 and 6.0 mg/kg per day) versus placebo and prednisone (0.75 mg/kg per day). Researchers plan to enroll 120 patients, with 30 patients in each arm.
ReveraGen BioPharma received funds for the present study from Actelion Pharmaceuticals, U.S. and European government agencies, and nonprofit foundations. Dr. Hoffman and some of his collaborators are cofounders of ReveraGen. Other coauthors received support from the company.
SOURCE: Hoffman EP et al. Neurology. 2019 Aug 26. doi: 10.1212/WNL.0000000000008168.