Edasalonexent, an NF-kB Inhibitor, Slows Longer-Term Disease Progression on Multiple Functional and MRI Assessments Compared to Control Period in 4 to 7-Year Old Patients with Duchenne Muscular Dystrophy (S51.006)

Objective: Edasalonexent is an orally administered small molecule inhibiting NF-kB under development for Duchenne muscular dystrophy (DMD). Background: NF-kB is fundamental to the initiation and progression of skeletal and cardiac muscle disease in DMD. Design/Methods: A Phase 2 trial with an open-label-extension enrolled 31 steroid-naive 4–7 year old (up to the 8th birthday) boys with DMD and studied edasalonexent at doses of 67 and 100 mg/kg. A prior off-treatment control period in most boys enabled off- and on-treatment comparisons. Data were analyzed after 72 weeks of edasalonexent treatment, and will be updated. Results: Disease progression in functional measures in the off-treatment control period corresponded with off-steroid natural history of boys of this age. With edasalonexent 100 mg/kg, there was stabilization in timed function tests (TFTs; 10-meter walk/run, time-to-stand and 4-stair climb) and North Star Ambulatory Assessment compared to the off-treatment control period. Muscle enzymes decreased beyond 12 weeks (p Conclusions: Treatment with edasalonexent substantially delayed disease progression compared to an off-treatment control period as assessed by functional and MRI measures, with changes in muscle enzymes and heart rate providing additional support of positive effects. Edasalonexent has the potential to be disease-modifying in DMD and does not appear to have the adverse effects associated with high-dose steroids. PolarisDMD, a Phase 3 study, is currently enrolling. Disclosure: Dr. Finkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals, Inc. and Biogen, AveXis, Novartis, and Roche. Dr. Finkel has received royalty, license fees, or contractual rights payments from Licensing fees from Children’s Hospital of Philadelphia for development of the CHOP-INTEND motor scale. Dr. Finkel has received research support from Ionis Pharmaceuticals, Inc. and Biogen, grants from AveXis and Cytokinetics. Dr. Vandenborne has received research support from Catabasis Pharmaceuticals. Dr. Sweeney has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Cytokinetics, Catabasis, and BMS. Dr. Sweeney has received research support from Catabasis Pharmaceuticals. Dr. Finanger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis (advisory board member), Bristol Myers Squibb (DMSB board member). Dr. Finanger has received research support from Catabasis, Sarepta Therapeutics, PTC, Fibrogen, Summitt, Italfarmaco, Biogen, AveXis. Dr. Tennekoon has received research support from Catabasis Pharmaceuticals. Dr. Shieh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, AveXis, Inc., Biogen, Grifols, PTC Therapeutics and Sarepta. Dr. Shieh has received research support from AveXis, Inc., Audentes, Biogen, Bristol-Myers Squibb, Cytokinetics, Catalyst, Fibrogen, Ionis Pharmaceuticals, Inc., Marathon, Pfizer, PTC Therapeutics, Sarepta, Santhera, Summit, Sanofi/Genzyme and Ultragenyx. Dr. Willcocks has nothing to disclose. Dr. Walter has received research support from Catabasis Pharmaceuticals. Dr. Rooney has nothing to disclose. Dr. Forbes has nothing to disclose. Dr. Triplett has nothing to disclose. Dr. Yum has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics. Dr. Mancini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis Pharmaceuticals. Dr. Mancini has received research support from Catabasis Pharmaceuticals. Dr. MacDougall has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis Pharmaceuticals. Dr. Fretzen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis Pharmaceuticals. Dr. Fretzen has received research support from Catabasis Pharmaceuticals. Dr. Bista has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis. Dr. Bista has received research support from Catabasis. Dr. Nichols has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis. Dr. Nichols has received research support from Catabasis. Dr. Donovan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Catabasis Pharmaceuticals. Dr. Donovan has received research support from Catabasis Pharmaceuticals.