Background: Edasalonexent, an oral NF-κB inhibitor, is being investigated as a potential foundational therapy for DMD patients regardless of mutation. Importantly, edasalonexent is not a steroid and does not impact the glucocorticoid receptor. High-dose steroids are associated with adverse effects (AE) related to bone health, growth and adrenal suppression, among other side effects.
Methods: In the MoveDMD Phase 2 randomized, placebo-controlled trial with open-label-extension enrolling 31 steroid-naïve 4-7 year old boys (<8th birthday) with DMD, edasalonexent was studied for up to 150 weeks of treatment. Measures of muscle function and MRI assessments of muscle integrity showed slowing of disease progression compared to an off-treatment control period. Safety measures included assessments of growth and impact on adrenal function (ACTH and cortisol). Fractures were recorded as part of safety monitoring.
Results: Edasalonexent was well-tolerated in the MoveDMD trial. Diarrhea was the most common treatment-related AE, generally mild and transient, and there were no serious AE on edasalonexent. There was no evidence of adrenal insufficiency with no clinically significant changes in either cortisol or ACTH. In over 60 patient-years of exposure, only two fractures were reported (radius and metatarsal), none with minimal trauma. Height increased along expected growth curves for unaffected boys, while weight increase was less than the mean for unaffected boys, resulting in overall normalized BMIs.
Conclusions: Treatment with edasalonexent was well tolerated and associated with favorable growth patterns without negative impact on bone health or adrenal function. Edasalonexent has the potential to be disease-modifying in DMD patients and in this Phase 2 trial did not have the adverse effects associated with high-dose steroids. An ongoing Phase 3 trial of edasalonexent, PolarisDMD, is fully enrolled and is further assessing safety and efficacy in young boys with DMD.