Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy

Background: Duchenne muscular dystrophy (DMD) patients experience skeletal muscle degeneration, including respiratory muscles. Respiratory decline in glucocorticoid-treated DMD patients, measured by percent predicted forced vital capacity (FVC%p), is typically 5% annually in patients aged 10 to 18 years. Objective: Evaluate the effects of eteplirsen on FVC%p annual change in 3 trials versus matched Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) controls. Methods: Eteplirsen studies 201/202 evaluated eligible ambulatory DMD patients for at least 4 years, study 204 evaluated primarily non-ambulatory DMD patients for 2 years, and ongoing study 301 is evaluating ambulatory DMD patients for 2 years (interim analysis is included). Eteplirsen-treated patients (n = 74) were amenable to exon 51 skipping and were receiving glucocorticoids. Three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (Exon 51 CINRG DNHS; n= 20), all glucocorticoid-treated CINRG patients (All CINRG DNHS; n = 172), and all glucocorticoidtreated genotyped CINRG DNHS patients (Genotyped CINRG DNHS; n = 148). FVC%p assessments between ages 10 and <18 years were included for all patients; mixed-model analyses characterized FVC%p annual change. Results: FVC%p annual change was greater for CINRG DNHS Exon 51 controls (-6.00) versus patients in studies 201/202, study 204, and study 301 (-2.19, P < 0.001; -3.66, P 0.004; and -3.79, P 0.017, respectively). FVC%p annual change in all eteplirsen studies suggested treatment benefit compared 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 versus CINRG DNHS controls.