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

Richard S. Finkel, Erika Finanger, Krista Vandenborne, H. Lee Sweeney, Gihan Tennekoon, Perry B. Shieh, Rebecca Willcocks, Glenn Walter, William D. Rooney, Sean C. Forbes, William T. Triplett, Sabrina W. Yum, Maria Mancini, James MacDougall, Angelika Fretzen, Pradeep Bista, Andrew Nichols, Joanne M. Donovan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)385-396
Number of pages12
JournalNeuromuscular Disorders
Volume31
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • Anti-inflammatory
  • CAT-1004
  • Duchenne muscular dystrophy
  • Edasalonexent
  • NF-κB

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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