Vamorolone maintains muscle strength, function in Duchenne muscular dystrophy

Vamorolone maintained muscle strength and function, as well as improved height velocity, compared with glucocorticoid therapy among those with Duchenne muscular dystrophy, according to data published in JAMA Network Open.

“Despite scientific advances, the only medications that have consistently demonstrated efficacy in clinical trials for [Duchenne muscular dystrophy (DMD)] are glucocorticoids (GCs), such as prednisone and deflazacort,” Jean K. Mah, MD, child health and wellness researcher and professor of pediatrics and clinical neurosciences at Alberta Children’s Hospital Research Institute at the University of Calgary in Canada, and colleagues wrote. “Most gene-targeted, disease-modifying technologies that are currently in development or have been recently approved focus on subsets of dystrophin variants and therefore do not address the unmet need among all individuals with DMD. Moreover, these treatments are prescribed in combination with and not as alternatives to GCs.

“The adverse outcomes associated with GCs, including weight gain, appearance associated with Cushing syndrome, short stature, behavior changes, low bone density, bone fractures and cataracts, negatively impact quality of life among individuals with DMD,” they added.

Mah and colleagues conducted a nonrandomized controlled trial at 11 U.S. and non-U.S. study sites and included 41 boys aged 4.5 to 7.5 years with DMD. Participants had previously completed the 6-month dose-finding study and were enrolled in a 24-month, long-term extension (LTE) study with vamorolone dose escalated to 2 or 6 mg/kg per day.

The primary outcome was change in time-to-stand (TTSTAND) velocity from dose-finding baseline to end of the LTE study, and efficacy assessments were performed using timed function tests, 6-minute walk test and the NorthStar Ambulatory Assessment (NSAA). Participants in the LTE study receiving higher doses of vamorolone were matched with data from two previous studies, the Duchenne Natural History Study (DNHS) and NorthStar United Kingdom (NSUK) Network, which included participants with DMD treated with glucocorticoids.

Vamorolone was found to be well tolerated at doses up to 6 mg/kg per day. However, there was no statistically significant change in TTSTAND from baseline to 30 months among the 21 participants treated with a vamorolone dose greater than or equal to 2 mg/kg per day consistently throughout the 6-month dose-finding and LTE studies (0.011 rises/s; 95% CI, 0.068-0.046 rises/s).

There were also no statistically significant differences observed between participants receiving higher-dose vamorolone and matched participants in the control groups receiving glucocorticoid treatment over a 2-year period in NSAA total score change, body mass index z score change or timed function test change.

Participants treated with vamorolone had stable height percentiles (0.37 percentile/mo; 95% CI, 0.23-0.52 percentile/mo) over time compared with participants in the DNHS, who were treated with glucocorticoids and had significant growth delay.

Vamorolone showed similar efficacy compared with standard-of-care glucocorticoid therapy up to 30 months without delaying growth in patients, suggesting that it may be an attractive candidate for treatment of DMD, according to Mah and colleagues.