Results from PolarisDMD, A Phase 3 Trial of Edasalonexent for Duchenne Muscular Dystrophy

Topic:

Clinical Trials

Poster Number: 74

Author(s):

Richard Finkel MD, Craig McDonald MD, Lee Sweeney PhD, Erika Finanger MD, Erin Neil MD, Kathryn R. Wagner , Katherine D. Mathews MD, Warren Marks MD, Jeffery Statland MD, Jessica Nance M.D., Hugh McMillan , Gary McCullagh , Cuixia Tian MD, Monique Ryan MD, Declan O'Rourke , Wolfgang Müller-Felber , Mar Tulinius , W. Bryan Burnette , Cam-Tu Nguyen , Kayal Vijayakumar , Jessika Johannsen , Michelle Eagle , Maria Mancini MHP, Joanne Donovan MD, PhD

Institutions:

1. Translational Neuroscience Program, St. Jude Children's Research Hospital, Memphis, TN, US, 2. University of California Davis, 3. University of Florida, 4. Oregon Health & Science University, 5. University of Michigan, 6. Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA, 7. University of Iowa, 8. Cook Children's Medical Center, 9. University of Kansas Medical Center, 10. Johns Hopkins Hospital, 11. Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada, 13. Cincinnati Children's Hospital Medical Center, 14. Department of Neurology, Royal Children’s Hospital, 16. Klinikum der Universität München, 17. Dept of Pediatrics, Gothenburg University, The Queen Silvia Children’s Hospital, Gothenburg, Sweden, 18. Vanderbilt University, 21. University Medical Center Hamburg-Eppendorf, Department for Pediatrics, 22. ATOM International, Ltd, Consett, UK, 23. Catabasis Pharmaceuticals, 24. Catabasis Pharmaceuticals

Background:
Edasalonexent is an oral NF-κB inhibitor developed for Duchenne muscular dystrophy (DMD).

Objectives:
The Phase 3 PolarisDMD trial was a 52-week randomized, double-blind, placebo-controlled trial designed to evaluate efficacy and safety of edasalonexent in boys with DMD aged 4-7 (up to 8th birthday).

Methods:
This global trial enrolled 131 boys with any mutation type, not on glucocorticoids or any investigational therapies, with a time-to-stand (TTS) ≤10s. Primary endpoint was change in North Star Ambulatory Assessment (NSAA). Additional endpoints included timed function tests (TFTs) TTS, 10-meter-walk/run (10MWR) and 4-stair climb (4SC), muscle strength, and parent-reported outcomes (PODCI). Growth and bone density were assessed, along with safety (labs, vitals, and adverse events [AE]).

Results:
Neither primary nor secondary endpoints were met at week 52. The NSAA difference between edasalonexent and placebo groups was 0.3 (SE=0.7; p=0.67). Though TTS, 10MWR and 4SC were faster for edasalonexent by 1.4, 0.3 and 1.0 seconds respectively, differences in speed of TFTs between groups were not statistically significant (all p>0.5). Muscle strength and PODCI were not statistically significant, nor were muscle enzymes and heart rate. Height increased as expected, with relatively less increase in weight than placebo.

In a prespecified subgroup analysis of boys aged ≤6, neither NSAA (p=0.08) nor 10MWR (p=0.41) reached significance, but improvements in TTS (p=0.046), 4SC (p=0.02) and PODCI (p=0.048) were observed. In boys aged >6, functional differences were not significant.

Most common AEs on edasalonexent were diarrhea, vomiting, and rash, and were mild and transient. There were two serious AEs (norovirus gastroenteritis on edasalonexent; bronchiolitis on placebo), neither treatment-related.

Conclusion:
The trial did not meet its primary or secondary endpoints; however, there were trends toward improvement, particularly in the younger subgroup. While edasalonexent was generally safe and well-tolerated, the totality of evidence does not support further development of edasalonexent for DMD.