Abstract Details

Title 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

Topic Child Neurology and Developmental Neurology

Presentation(s) S51 - Child Neurology: Bench to Bedside: Progress in Treating Genetic Disorders (4:25 PM-4:36 PM)

Poster/Presentation
Number 006

Background NF-kB is fundamental to the initiation and progression of skeletal and cardiac muscle disease in DMD.

Objective Edasalonexent is an orally administered small molecule inhibiting NF-kB under development for Duchenne muscular dystrophy (DMD).

Design/Methods A Phase 2 trial with an open-label-extension enrolled 31 steroid-naïve 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<0.05), as did C-reactive protein, a biomarker of inflammation (p<0.05). A composite of lower leg muscle MRI-T2, a measure that has been shown to be highly correlated with function and loss of functional milestones, showed stabilization compared to off-treatment progression (p<0.05). Additionally, the rate of fat accumulation in the vastus lateralis and soleus muscles as measured by MRS decreased compared to the off-treatment period. Edasalonexent was well tolerated at all doses without safety signals. Height and weight increased age-appropriately, while heart rate declined toward age-normative values (p<0.05).

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.

Authors/Disclosures
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital) PRESENTER	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
Erika L. Finanger, MD (Oregon Health Science University, Child Neurology)	Dr. Finanger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics. Dr. Finanger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Finanger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reata. Dr. Finanger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer.
Gihan Tennekoon, MD (Children's Hosp of Philadelphi)	No disclosure on file
Perry Shieh, MD, PhD, FAAN (UCLA)	Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Catalyst.
	No disclosure on file
	No disclosure on file
William Rooney, PhD (Oregon Health & Science University)	Dr. Rooney has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Maria Mancini (Edgewise Therapeutics)	No disclosure on file
	No disclosure on file
	No disclosure on file
Pradeep Bista (Biogen Idec)	No disclosure on file
	No disclosure on file
Joanne Donovan, MD, PhD (Catabasis Pharmaceuticals)	No disclosure on file

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