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