Abstract Details

Title Delays in Progression of Duchenne Muscular Dystrophy with Eteplirsen Treatment: Attenuation of Pulmonary Function Decline and Projected Freedom from Continuous Ventilation

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S6 - Neuromuscular and Clinical Neurophysiology (EMG): Genetic Muscle Disorders (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Objective

In this study, we compare temporal patterns of forced vital capacity % predicted (FVC%p) and projected time to continuous ventilation in Duchenne muscular dystrophy (DMD) patients receiving eteplirsen versus standard of care (SoC).

Background

DMD is a rare genetic disorder characterized by progressive muscle degeneration leading to loss of ambulation and respiratory failure. Eteplirsen is indicated to treat DMD with genetic mutations amenable to exon 51 skipping.

Design/Methods DMD patients with exon 51 skippable mutations treated with eteplirsen or SoC were considered for this analysis. Eteplirsen-treated patients were from Study 204 (N=20) and a subsequent larger efficacy study (Study 301, N=42). SoC patients were drawn from the Cooperative International Neuromuscular Research Group (CINRG) database (N=20). A mixed effects model with repeated measures was used to evaluate the impact of eteplirsen on the decline in FVC%p. The analysis included glucocorticoid-treated patients between 10 and 18 years of age. The model fit FVC%p as the response variable, treatment group (eteplirsen vs. control), age (at visit), and the interaction between treatment group and age as the fixed effects, and patient as a random effect. Time to continuous diurnal ventilation (FVC%p < 30%) was predicted using a linear extrapolation of the model estimated decline in FVC%p from the average FVC%p readings observed between 10-10.5 years old for patients who are treated with glucocorticoid steroids in the specified trials.

Results

Eteplirsen-treated patients experienced a statistically significant attenuation in the FVC%p decline compared to SoC patients (annual rate of decline of 3.82% vs. 5.96%, respectively; P<0.01). Assuming an average starting FVC%p of ~77.82% at age 10, a decline in FVC%p for eteplirsen corresponds to a delay of ~4.5 years in time to needing continuous ventilation vs. SoC patients.

Conclusions Eteplirsen treatment was associated with significant attenuation of pulmonary decline based on FVC%p and clinically meaningful projected time to continuous ventilation.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Erik K. Henricson, MPH (University of California Davis)	No disclosure on file
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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