Eteplirsen treatment attenuates respiratory decline in ambulatory and non-ambulatory patients with duchenne muscular dystrophy

Navid Khan, Helen Eliopoulos, Lixin Han, T. Bernard Kinane, Linda P. Lowes, Jerry R. Mendell, Heather Gordish-Dressman, Erik K. Henricson, Craig M. McDonald

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 glucocorticoid-treated 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.

Original languageEnglish (US)
Pages (from-to)213-225
Number of pages13
JournalJournal of Neuromuscular Diseases
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Dystrophin
  • Exondys 51
  • forced expiratory volume
  • vital capacity

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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