@article{c85949007780423688d1967dc607190f,
title = "Disease-modifying effects of edasalonexent, an NF-κB inhibitor, in young boys with Duchenne muscular dystrophy: Results of the MoveDMD phase 2 and open label extension trial",
abstract = "Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy. Edasalonexent (CAT-1004) is an orally-administered novel small molecule that covalently links two bioactive compounds (salicylic acid and docosahexaenoic acid) that inhibit NF-κB. This placebo-controlled, proof-of-concept phase 2 study with open-label extension in boys ≥4-<8 years old with any dystrophin mutation examined the effect of edasalonexent (67 or 100 mg/kg/day) compared to placebo or off-treatment control. Endpoints were safety/tolerability, change from baseline in MRI T2 relaxation time of lower leg muscles and functional assessment, as well as pharmacodynamics and biomarkers. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly of the gastrointestinal system (primarily diarrhea). There were no serious adverse events in the edasalonexent groups. Edasalonexent 100 mg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-κB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.",
keywords = "Anti-inflammatory, CAT-1004, Duchenne muscular dystrophy, Edasalonexent, NF-κB",
author = "Finkel, {Richard S.} and Erika Finanger and Krista Vandenborne and Sweeney, {H. Lee} and Gihan Tennekoon and Shieh, {Perry B.} and Rebecca Willcocks and Glenn Walter and Rooney, {William D.} and Forbes, {Sean C.} and Triplett, {William T.} and Yum, {Sabrina W.} and Maria Mancini and James MacDougall and Angelika Fretzen and Pradeep Bista and Andrew Nichols and Donovan, {Joanne M.}",
note = "Funding Information: The authors thank the subjects and their families for their participation, and the staff of the clinical research organizations at each study site, including study coordinators, clinical evaluators, co-investigators, and pharmacists, for conduct of the studies, and gratefully acknowledge colleagues at Catabasis Pharmaceuticals, Inc. for their contributions to the development of edasalonexent. The authors acknowledge Donovan Lott, PT, PhD, CSCS for his role in training the clinical assessors who performed the functional assessments, John Sladky, MD and Peter B. Kang, MD for contributions to study management, and Barry S. Russman, MD for contributions to study design. All authors participated in the design, conduct, and analysis of the study, and manuscript development and approved the final manuscript. Catabasis Pharmaceuticals, Inc. provided financial support for the conduct of the research and data analyses. Patrice C. Ferriola, PhD, of KZE PharmAssociates, LLC provided medical writing assistance and was funded by Catabasis Pharmaceuticals, Inc. Gigi Shafai, PharmD provided editorial review as an employee of Catabasis Pharmaceuticals. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = may,
doi = "10.1016/j.nmd.2021.02.001",
language = "English (US)",
volume = "31",
pages = "385--396",
journal = "Neuromuscular Disorders",
issn = "0960-8966",
publisher = "Elsevier Limited",
number = "5",
}