Abstract Details

Title Eteplirsen-Treatment Attenuates Respiratory Decline in Ambulatory and Non-ambulatory Patients With Duchenne Muscular Dystrophy: Comparison With Natural History Cohorts

Topic Child Neurology and Developmental Neurology

Presentation(s) S51 - Child Neurology: Bench to Bedside: Progress in Treating Genetic Disorders (4:14 PM-4:25 PM)

Poster/Presentation
Number 005

Background Patients with Duchenne muscular dystrophy (DMD) experience progressive degeneration of skeletal muscles, including respiratory muscles. Respiratory decline in glucocorticoid-treated patients with DMD, measured by FVC%p, is typically 5% annually in patients aged 10 to 18 years.

Objective We evaluated the effect of eteplirsen treatment on the annual change in percent predicted forced vital capacity (FVC%p) in 3 eteplirsen clinical trials compared with well-matched natural history controls from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS).

Design/Methods

Eteplirsen Studies 201 and 202 evaluated eligible ambulatory DMD patients for at least 4 years, Study 204 evaluated primarily non-ambulatory DMD patients for 2 years, and the ongoing Study 301 is evaluating eteplirsen treatment of ambulatory DMD patients for 96 weeks, followed by a 48-week safety extension (interim Week 96 analysis is presented). Eteplirsen-treated patients (n=74) were amenable to exon 51 skipping and were receiving glucocorticoids. Three CINRG DNHS cohorts were included: glucocorticoid-treated patients amenable to exon 51 skipping (Exon 51 CINRG DNHS; n=20), all glucocorticoid-treated patients (All CINRG DNHS; n=172), and all glucocorticoid-treated genotyped CINRG DNHS patients (Genotyped CINRG DNHS; n=148). FVC%p assessments from the ages of 10 to <18 years were included for all patients. Age-based mixed-model analyses were conducted to determine FVC%p annual change (slope) for the eteplirsen-treated patients and CINRG controls.

Results FVC%p annual change was greater for CINRG DNHS Exon 51 controls (−6.00) versus patients in Studies 201/202, 204, and 301 (−2.19, P<0.001; −3.66, P=0.004; and −3.79, P=0.017; respectively). The annual change in FVC%p in all eteplirsen studies compared favorably with the Genotyped CINRG DNHS (−5.67) and All CINRG DNHS (−5.56) cohorts (P<0.05, all comparisons).

Conclusions Significant, clinically meaningful attenuation of FVC%p decline was observed in eteplirsen-treated patients compared with CINRG controls across 3 clinical trials in both ambulatory and non-ambulatory DMD patients.

Authors/Disclosures
PRESENTER	No disclosure on file
Navid Khan	No disclosure on file
	No disclosure on file
Heather Gordish-Dressman	Heather Gordish-Dressman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AGADA Biosciences. Heather Gordish-Dressman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Solid Biosciences. Heather Gordish-Dressman has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for TRiNDS, LLC. Heather Gordish-Dressman has received personal compensation in the range of $500-$4,999 for serving as a Statistical reviewer with TREAT-NMD TACT Committee.
Linda P. Lowes, PT PhD	The institution of Ms. Lowes has received research support from Sarepta Therapeutics.
Craig McDonald, MD (UC Davis Dept. of PM&R)	Dr. McDonald has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PTC Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Solid Biosciences. Dr. McDonald has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Sarepta Therapeutics. The institution of Dr. McDonald has received research support from PTC Therapeutics. The institution of Dr. McDonald has received research support from Edgewise Therapeutics. The institution of Dr. McDonald has received research support from Capricor Therapeutics. The institution of Dr. McDonald has received research support from Italfarmaco. Dr. McDonald has received research support from NS Pharma. The institution of Dr. McDonald has received research support from NIH (NINDS). The institution of Dr. McDonald has received research support from Parent Project Muscular Dystrophy. The institution of Dr. McDonald has received research support from Muscular Dystrophy Association. Dr. McDonald has received personal compensation in the range of $500-$4,999 for serving as a Member National Advisory Board for Medical Rehabilitation Research with NIH.

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