Vamorolone demonstrates efficacy, safety for boys with Duchenne muscular dystrophy

Treatment with vamorolone, an anti-inflammatory steroidal drug, improved motor outcomes in boys with Duchenne muscular dystrophy compared with corticosteroid-naive individuals, according to findings published in PLoS Medicine.

Vamorolone (ReveraGen)also resulted in fewer physician-reported adverse events compared with the number reported for treatment with prednisone and deflazacort and did not result in the stunting of growth that has been observed with these corticosteroids, the researchers reported.

“Treatment with corticosteroids is recommended for [patients with Duchenne muscular dystrophy (DMD)] to slow the progression of weakness. However, chronic corticosteroid treatment causes significant morbidities,” the researchers wrote. “Vamorolone is a first-in-class anti-inflammatory investigational drug that has shown evidence of efficacy in DMD after 24 weeks of treatment at [2 or 6 mg/kg per day]. Here, open-label efficacy and safety experience of vamorolone was evaluated over a period of 18 months in trial participants with DMD.”

Edward C. Smith, MD, associate professor of pediatrics and neurology in the department of pediatrics at Duke University School of Medicine, and colleagues performed a multicenter, open-label, 24-week trial (VBP15-003) with a 24-month long-term extension (VBP15-LTE) that assessed drug-related effects of vamorolone on motor outcomes and corticosteroid-related safety events. They conducted the trial in Canada, the U.S., the U.K., Australia, Sweden and Israel from 2016 to 2019. The present study focused on the preliminary 24-week trial and the first 12 months of the VBP15-LTE trial, for a total treatment period of 18 months.

The researchers found that, among participants (boys with DMD aged 4 to <7 years of age at entry) who received vamorolone 2 mg/kg per day or 6 mg/kg per day for the full 18-month study period, there were clinical improvements in all motor outcomes from baseline to month 18. This included time to stand velocity (95% CI, 0.010-0.068 event/second), run/walk 10 meters velocity (95% CI, 0.220-0.491 meters/second), climb 4 stairs velocity (95% CI, 0.034-0.105 event/second), 6-minute walk test (95% CI, 31.14-93.38 meters) and the NorthStar Ambulatory Assessment (95% CI, 2.702-6.662 points).

Smith and colleagues also compared outcomes in patients with DMD who received vamorolone (n = 46) with group-matched participants in the CINRG Duchenne Natural History Study, which included 19 patients who were corticosteroid-naive and 68 patients who had received corticosteroids, over a similar 18-month period. This comparison demonstrated that time to stand was not significantly different between vamorolone-treated patients and corticosteroid-naive patients (least squares [LS] mean, 0.042; 95% CI, –0.007 to 0.091). However, vamorolone-treated participants exhibited significant improvement compared with group-matched, corticosteroid-naive participants regarding run/walk 10 meters velocity (LS mean, 0.286; 95% CI, 0.104-0.469) and climb 4 stairs velocity (LS mean, 0.059; 95% CI, 0.007-0.111). The vamorolone-related improvements were similar in magnitude to corticosteroid-related improvements, Smith and colleagues noted.

Patients treated with corticosteroids demonstrated stunting of growth, while participants who received vamorolone did not (LS mean, 15.86; 95% CI, 8.51-23.22). Physician-reported adverse events for Cushingoid appearance, hirsutism, weight gain and behavior changes were less with vamorolone compared with published rates of adverse events associated with prednisone and deflazacort.

The researchers acknowledged several limitations in the present study, including the open-label design and the indirect comparisons to previous research.

“However, long-term placebo arms in a rare pediatric disease such as DMD are considered unethical,” Smith and colleagues wrote.

The researchers also reported that a double-blind study is ongoing. That study includes 120 participants with DMD who are enrolled into four groups (vamorolone 2 mg/kg per day and 6 mg/kg per day, placebo and prednisone 0.75 mg/kg per day) and will provide Class I evidence regarding the safety and efficacy of vamorolone, according to Smith and colleagues.

Regarding the present study, the researchers wrote that it provides “Class IV evidence that, for boys with DMD, vamorolone treatment for 18 months shows possible efficacy compared [with] a natural history cohort of corticosteroid-naive patients and appears to be well tolerated, with fewer safety concerns than typically seen with long-term standard-of-care corticosteroid treatment.”