A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial

Richard S. Finkel, Craig M. McDonald, H. Lee Sweeney, Erika Finanger, Erin Neil Knierbein, Kathryn R. Wagner, Katherine D. Mathews, Warren Marks, Jeffrey Statland, Jessica Nance, Hugh J. McMillan, Gary McCullagh, Cuixia Tian, Monique M. Ryan, Declan O'Rourke, Wolfgang Müller-Felber, Mar Tulinius, W. Bryan Burnette, Cam Tu Nguyen, Kayal VijayakumarJessika Johannsen, Han C. Phan, Michelle Eagle, James MacDougall, Maria Mancini, Joanne M. Donovan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD). Objective: This international, randomized 2: 1, placebo-controlled, phase 3 study in patients ≥4-< 8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks. Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA; primary) and timed function tests (TFTs; secondary). Assessment of health-related function used the Pediatric Outcomes Data Collection tool (PODCI). Results: One hundred thirty one patients received edasalonexent (n = 88) and placebo (n = 43). At week 52, differences between edasalonexent and placebo for NSAA total score and TFTs were not statistically significant, although there were consistently less functional declines in the edasalonexent group. A pre-specified analysis by age demonstrated that younger patients (≤6.0 years) showed more robust and statistically significant differences between edasalonexent and placebo for some assessments. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly involved the gastrointestinal system (primarily diarrhea). Conclusions: Edasalonexent was generally well-tolerated with a manageable safety profile at the dose of 100 mg/kg/day. Although edasalonexent did not achieve statistical significance for improvement in primary and secondary functional endpoints for assessment of DMD, subgroup analysis suggested that edasalonexent may slow disease progression if initiated before 6 years of age.

Original languageEnglish (US)
Pages (from-to)769-784
Number of pages16
JournalJournal of Neuromuscular Diseases
Volume8
Issue number5
DOIs
StatePublished - 2021

Keywords

  • age effects
  • CAT-1004
  • Duchenne muscular dystrophy
  • edasalonexent
  • NF-κB

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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