Abstract
Introduction: ACT DMD was a 48-week trial of ataluren for nonsense mutation Duchenne muscular dystrophy (nmDMD). Patients received corticosteroids for ≥6 months at entry and stable regimens throughout study. This post hoc analysis compares efficacy and safety for deflazacort and prednisone/prednisolone in the placebo arm. Methods: Patients received deflazacort (n = 53) or prednisone/prednisolone (n = 61). Endpoints included change from baseline in 6-minutewalk distance (6MWD), timed function tests, estimated age at loss of ambulation (extrapolated from 6MWD). Results: Mean changes in 6MWD were -39.0 m (deflazacort; 95%confidence limit [CL], -68.85, -9.17) and -70.6 m (prednisone/prednisolone; 95% CL, -97.16, -44.02).Mean changes in 4-stair climb were 3.79 s (deflazacort; 95% CL, 1.54, 6.03) and 6.67 s (prednisone/prednisolone; 95% CL, 4.69, 8.64). Conclusions: This analysis, limited by its post hoc nature, suggests greater preservation of 6MWD and 4-stair climb with deflazacort vs. prednisone/prednisolone. A head-to-head comparisonwill better define these differences.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 639-645 |
| Number of pages | 7 |
| Journal | Muscle and Nerve |
| Volume | 58 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2018 |
Bibliographical note
Funding Information:We thank the patients and their families for their participation in this study; individuals who were instrumental in the conduct of this study and the collection of data, particularly principal investigators, supporting investigators, clinical coordinators, clinical evaluators, and study coordinators. We thank Robert Weiss (University of Utah, UT, USA) for dystrophin gene sequencing; the patient advocacy organizations (including Valerie Cwik and the Muscular Dystrophy Association, and Patricia Furlong and the Parent Project Muscular Dystrophy) for the collaboration and support that made this trial possible. Medical writing was provided by Annette Skorupa, PhD of EnlightenMed LLC and was funded by PTC Therapeutics, Inc.
Funding Information:
Conflicts of Interest: Dr. Darras has served as an ad hoc scientific advisory board member for AveXis, Biogen, Cytokinetics, Marathon Pharmaceuticals, PTC Therapeutics, Bristol-Myers Squibb, Roche, and Sarepta; and has been an advisor for Ionis Pharmaceuticals, Inc.; he has no financial interests in these companies. He has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, the Spinal Muscular Atrophy Foundation, CureSMA, and Working on Walking Fund; and grants from Ionis Pharmaceuticals, Inc. for the ENDEAR, CHERISH, CS2/CS12 studies, from Biogen for CS11, as well as from Cytokinetics, Sarepta Pharmaceuticals, PTC Therapeutics, Fibrogen, and Summit. Dr. Shieh has served as an ad hoc advisory board member for AveXis, Biogen, Marathon, PTC, and Sar-epta but he has no financial interests in these companies. He has received research support from Ionis Pharmaceuticals and Biogen for their SMA studies, as well as from Cytokinetics for their SMA clinical trial, Sarepta for the DMD clinical trials, PTC Therapeutics for their DMD/ataluren trial, Pfizer for their DMD/myostatin clinical trial, BMS/Roche for their DMD/myostatin clinical trial, Sanofi/Genzyme for their Pompe clinical trial, and Summit for their DMD clinical trial. Dr. McDonald has served as a consultant for clinical trials for PTC Therapeutics, Biomarin, Sarepta, Eli Lilly, Pfizer, Santhera Pharmaceuticals, Cardero Therapeutics, Inc., Catabasis, Capricor, Marathon, and Mitobridge, outside the submitted work; serves on external advisory boards related to Duchenne muscular dystrophy for PTC Therapeutics, Eli Lilly, Sar-epta Therapeutics, Santhera Pharmaceuticals, and Capricor; and reports grants from US Dept. of Education/NIDRR, NIDILRR, US NIH/NIAMS, US Department of Defense, and Parent Project Muscular Dystrophy US, during the conduct of the study. Joseph McIntosh, Fengbin Jin, Gary Elfring, Mar-cio Souza, Siva Narayanan, Panayiota Trifillis, and Stuart W. Peltz are employees and stockholders of PTC Therapeutics, Inc.
Publisher Copyright:
© 2018 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.
Keywords
- Deflazacort
- Muscular dystrophy
- Prednisolone
- Prednisone
- Walking