Meta-Analysis of Deflazacort vs Prednisone/Prednisolone in Patients with Duchenne Muscular Dystrophy (P2.325)

Objective: To compare the efficacy of deflazacort vs prednisone/prednisolone in a posthoc meta-analysis of a phase 2b and phase 3 study.

Background: Corticosteroids can slow the loss of motor function in patients with Duchenne muscular dystrophy (DMD) and are considered part of the standard of care. The phase 2b (Study 007) and phase 3 (ACT DMD) clinical trials of ataluren are the largest, randomized, double-blind, placebo-controlled studies in nonsense mutation DMD to date.

Design/Methods: In a meta-analysis of the placebo arm of a phase 2b and phase 3 study, evidence comparing the efficacy of deflazacort vs prednisone/prednisolone was assessed post-hoc using the 6 minute walk test (6MWT) in patients with phenotypic and genotypic evidence of DMD aged ≥ 7 y, a baseline 6-minute walk distance (6MWD) ≥ 150 m, and ≤80% of predicted for their age and height. Patients in the placebo arms of each study received deflazacort (n=64) or prednisone/prednisolone (n=82) for 48 weeks after being on that same treatment for ≥12 months prior to the study start. The primary endpoint was change from baseline to week 48 in 6MWD. Safety parameters were also assessed.

Results: The weighted estimate of the treatment differences in 6 MWD (m, ±SEM) is 34.1m ± 13.5m and 95% CI of 7.6 to 60.7, showing a significant difference (p=0.006) favoring deflazacort. Respective adverse events ≥10% for deflazacort or prednisone/prednisolone were: vomiting (21.9%, 19.5%) headache (18.8%, 20.7%), nasopharyngitis (12.5%, 24.4%), fall (14.1%, 18,3%) diarrhea (12.5%, 14.6%), upper abdominal pain (7.8%, 17.1%), cough (9.4%, 15.9%), pain in extremity (12.5%, 11.0%), pyrexia (9.4%, 12.2%).

Conclusions: Deflazacort appeared to be more effective than prednisone/prednisolone in delaying progression of DMD.

Study Supported by: PTC Therapeutics, Inc

Disclosure: Dr. Riebling has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics. Dr. O'Mara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Elfring has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Luo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Trifillis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. McIntosh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics. Dr. McIntosh holds stock and/or stock options in PTC Therapeutics. Dr. Santos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Parsons has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, AveXis, Sarepta. Dr. Parsons has received research support from Biogen, AveXis, PTC, Sarepta. Dr. Shieh has nothing to disclose. Dr. Apkon has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Apkon has received research support from PTC, Sarepta, and Eli Lilly and Marathon Pharm. Dr. Campbell has nothing to disclose. Dr. McDonald has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC, Santhera, Sarepta, Catabasis, Mitobridge, Cardero, Capricor. Dr. McDonald has received research support from PTC, Sarepta, Santhera, Pfizer, Marathon.