VANCOUVER, BC—Deflazacort and prednisone improved biomarkers of muscle breakdown versus placebo in boys with Duchenne muscular dystrophy (DMD), according to results of a randomized Phase 3 study reported at the 68th AAN Annual Meeting.
In addition, when deflazacort 0.9mg/kg/day was compared with prednisone, continued improvement over 1 year was seen among those with increased numeric improvements, Jordan Dubow, MD, Chief Medical Officer, Marathon Pharmaceuticals, Northbrook, IL, and colleagues stated.
Previously, corticosteroids such as deflazacort and prednisone have been shown “to prolong independent ambulation, improve pulmonary function, delay the onset of cardiomyopathy, and reduce the incidence of scoliosis” in those with Duchenne muscular dystrophy, an X-linked disease affecting about 1 in 5,000 live male births, they noted.
To evaluate the efficacy of these treatments, Dr. Dubow and colleagues conducted a Phase 3, randomized, double-blind, placebo-controlled, active-comparator study that randomized 196 participants from 9 centers to 1 of 4 treatment groups for 12 weeks: deflazacort 0.9mg/kg/day, deflazacort 1.2mg/kg/day, prednisone 0.75mg/kg/day, and placebo. The primary efficacy endpoint was the difference in change from baseline to 12 weeks in average muscle strength as assessed by a modified Medical Research Council Scale with active treatment vs. placebo.
They then compared deflazacort 0.9 and 1.2mg/kg/day to prednisone 0.75mg/kg/day from 12 to 52 weeks.
At baseline, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) were comparable among the groups.
At Week 6, AST, CK, and LDH were significantly decreased with both deflazacort doses and prednisone compared to placebo: AST: -30, -51, -49, and +14, respectively; CK: -3529, -2895, -3748, and +840, respectively; and LDH: -226, -207, -196, and +92, respectively (P<0.05), they reported.
From baseline to Week 52, CK and LDH stayed below baseline for all treatment groups, while for AST, deflazacort 0.9mg/kg/day and prednisone remained below baseline values. The deflazacort 0.9mg/kg/day group demonstrated numerically greater improvement than prednisone after 52 weeks regarding LDH, CK, and AST though these differences did not reach statistical significance.
Patients in the deflazacort treatment arms had significantly less weight gain and less discontinuations due to weight gain than the prednisone treatment arm. In addition, patients treated with deflazacort experienced a lower incidence of cushingoid-type and psychiatric adverse events than the those treated with prednisone.
Dr. Dubow concluded, “Although increased muscle enzyme activity does not always correlate with disease severity, the reduction in muscle enzymes with the use of corticosteroids reflects their underlying anti-inflammatory effect on muscle which translates to improvement in motor strength and function.”