Deflazacort, a glucocorticoid drug, was shown to improve muscle strength in boys with Duchenne muscular dystrophy (DMD) in a clinical trial performed by Marathon Pharmaceuticals. Trial results were reported in a presentation, “Effect of DEFLAZACORT and PREDNISONE versus placebo on muscle strength in boys with duchenne muscular dystrophy who have lost ambulation: results from the deflazacort clinical trial program,” at the recent 2016 MDA Clinical Conference held in Arlington, Virginia.
DMD is a genetic disorder caused by mutations in the dystrophin gene, which leads to myofiber degeneration and muscle wasting. Affecting mainly boys (1 in 5,000 male births), symptoms usually arise between 3 to 5 years of age and patients lose ambulation between the ages of 9 and 12. Currently, the only therapeutic available is glucocorticoids, which can increase patients’ muscle strength.
Deflazocort, a glucocorticoid that belongs to the class of oxazoline steroids, has previously been shown to possess anti-inflammatory and immunosuppressant effects. Additionally, its efficacy is equivalent to prednisone (a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug), and causes less weight gain.
Marathon Pharmaceuticals‘ researchers designed a clinical trial to assess the effects of deflazacort and prednisone on muscle strength in boys with DMD who had lost the ability to walk. The randomized, double-blind, placebo-controlled study evaluated 196 patients, who were randomized to received either deflazacort 0.9 mg/kg/day, deflazacort 1.2 mg/kg/day, prednisone 0.75 mg/kg/day, or placebo. In a first phase of the study, researchers assessed deflazacort and prednisone treatment effects against placebo after 12 weeks; in a second phase, they compared the two doses of deflazacort to prednisone from 12 to 52 weeks.
Results showed that both deflazacort and prednisone improved muscle strength after 12 weeks of treatment in DMD boys. Moreover, during the 52 weeks of treatment, both doses of deflazacort improved and helped maintain muscle strength more effectively than prednisone. Weight gain was also significantly higher with prednisone compared to both doses of deflazacort over the 52 weeks.
These results reveal that corticosteroid therapy after loss of ambulation may have motor function benefits. When comparing both prednisone and deflazacort, the latter has both safety and efficacy advantages. A future larger, prospective trial is currently being designed to continue to evaluate the effects of deflazacort in DMD boys who have lost ambulation.