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

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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Duchenne Muscular Dystrophy
Natural History
Vital Capacity
Research
Glucocorticoids
Therapeutics
Exons
Cohort Studies
Respiratory Muscles
Skeletal Muscle

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Eteplirsen treatment attenuates respiratory decline in ambulatory and non-ambulatory patients with duchenne muscular dystrophy. / Khan, Navid; Eliopoulos, Helen; Han, Lixin; Kinane, T. Bernard; Lowes, Linda P.; Mendell, Jerry R.; Gordish-Dressman, Heather; Henricson, Erik K; McDonald, Craig M.

In: Journal of Neuromuscular Diseases, Vol. 6, No. 2, 01.01.2019, p. 213-225.

Research output: Contribution to journalArticle

Khan, Navid ; Eliopoulos, Helen ; Han, Lixin ; Kinane, T. Bernard ; Lowes, Linda P. ; Mendell, Jerry R. ; Gordish-Dressman, Heather ; Henricson, Erik K ; McDonald, Craig M. / Eteplirsen treatment attenuates respiratory decline in ambulatory and non-ambulatory patients with duchenne muscular dystrophy. In: Journal of Neuromuscular Diseases. 2019 ; Vol. 6, No. 2. pp. 213-225.
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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.",
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author = "Navid Khan and Helen Eliopoulos and Lixin Han and Kinane, {T. Bernard} and Lowes, {Linda P.} and Mendell, {Jerry R.} and Heather Gordish-Dressman and Henricson, {Erik K} and McDonald, {Craig M}",
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AU - Khan, Navid

AU - Eliopoulos, Helen

AU - Han, Lixin

AU - Kinane, T. Bernard

AU - Lowes, Linda P.

AU - Mendell, Jerry R.

AU - Gordish-Dressman, Heather

AU - Henricson, Erik K

AU - McDonald, Craig M

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N2 - 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.

AB - 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.

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