Marathon Pharmaceuticals recently presented findings from a Phase 3 trial comparing the effects of deflazacort to prednisone and placebo in boys with Duchenne muscular dystrophy. The presentation, showing deflazacort was more effective than prednisone in timed functional tests and in limiting weight gain, was given at the 2016 Muscular Dystrophy Association (MDA) Clinical Conference, and will be shown again at the 68th AAN Annual Meeting, taking place April 15–21 in Vancouver, Canada.
Duchenne muscular dystrophy (DMD) is an X-chromosome-linked and rapidly progressive form of muscular dystrophy that occurs primarily in boys. Currently, glucocorticoids are the only treatment shown to increase muscle strength in patients. These drugs also improve pulmonary function and delay the occurrence of cardiomyopathy. Deflazacort (DFZ) is a heterocyclic glucocorticoid with demonstrated anti-inflammatory and immunosuppressant effects. Previous studies have shown that deflazacort is as effective as prednisone in DMD treatment, while causing less weight gain.
Recently, Marathon Pharmaceuticals completed a relative bioavailability study comparing its tablet formulation to Calcort (DFZ tablets from Sanofi), with results revealing the two tablets are bioequivalent.
Researchers at Marathon designed and conducted the randomized, double-blind and placebo-controlled Phase 3 study to compare deflazacort to prednisone and placebo. Boys ages 5 to 15 were randomized to receive deflazacort 0.9 mg/ kg/day, deflazacort 1.2 mg/kg/day, prednisone 0.75 mg/ kg/day, or placebo. The study’s first segment compared deflazacort and prednisone to placebo over 12 weeks, while the second segment — weeks 12 to 52 — compared the two doses of deflazacort to prednisone. The study’s primary efficacy endpoint was the difference in change, from baseline to week 12, in average muscle strength as assessed by a modified Medical Research Council Scale. Secondary efficacy endpoints included overall physical condition, timed functional test results, and, specifically, the change from week 12 to 52 in average muscle strength, and the change from baseline to week 52 in average muscle strength. Adverse events and vital signs were also assessed.
Results indicated the primary endpoint was met, with both doses of deflazacort and prednisone shown to be superior to placebo at 12 weeks in improving muscle strength. The two drugs were also superior to placebo at week 12 in timed functional tests, with boys in both deflazacort groups and in the prednisone group showing “significant improvement” over those in the placebo group. Continued benefit was seen over the 52 weeks of treatment.
Both deflazacort dosing groups were significantly better than the prednisone group in a timed test of climbing four stairs, measured from baseline to week 52, but only the highest dose group showed a trend toward significance compared to prednisone in a test of running/walking 30 feet. Both deflazacort groups were also reported to have a lower incidence of cushingoid-type and psychiatric adverse events compared to prednisone. Furthermore, in line with published literature, deflazacort-treated patients gained significantly less weight compared to boys on prednisone, and had fewer treatment discontinuations due to weight gain than prednisone.
“Data from this study may be important to physicians when deciding which corticosteroid to use in boys with DMD,” the researchers concluded.
According to the National Human Genome Research Institute, DMD occurs in approximately 1 in every 3,500 male births worldwide.
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