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New Analysis Shows Drug Slows Down Respiratory Decline in Patients with Duchenne Muscular Dystrophy in Three Clinical Trials

Comparison of clinical trial results with prospective natural history data published in the Journal of Neuromuscular Diseases show supportive results for eteplirsen in delaying respiratory decline

July 9, 2019
Amsterdam, NL – Duchenne muscular dystrophy occurs in boys and is characterized by progressive muscle degeneration and weakness leading to a decline in respiratory function. Strategies to arrest this severe progressive deterioration are needed to extend lives and improve quality of life. Results of three clinical trials using eteplirsen, an exon-skipping antisense oligonucleotide, show promising results, according to a study published in the Journal of Neuromuscular Diseases.

Muscular dystrophy is a group of genetic disorders that results in increasing weakening and breakdown of skeletal muscles. Near absence of dystrophin, a critical protein, results in inflammation, necrosis, and eventual replacement of functional muscle tissue with fibrosis and fat. Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy in boys that has a predictable disease course. Muscle weakness usually begins around the age of four in the thighs and pelvis followed by the arms. Most patients are unable to walk by the age of 12. Natural history data show that respiratory function declines linearly and predictably in the second decade of life. Respiratory decline in glucocorticoid-treated DMD patients is typically 5% annually in patients aged 10 to 18 years. Patients require increasing levels of clinical intervention as the disease progresses.

Investigators led by Navid Z. Khan, PhD, Senior Director, Global Medical Affairs, Sarepta Therapeutics, Inc., Cambridge, MA, USA, evaluated respiratory function in eteplirsen-treated patients from three clinical trials and compared them to patients matched by age range, steroid use, and genotype from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) global database. These three trials studied eligible ambulatory DMD patients for at least four years (studies 201 and 202), primarily non-ambulatory DMD patients for two years (study 204), and an ongoing open label multicenter study of ambulatory DMD patients aged seven to 16 years (study 301).

The CINRG DNHS, one of the largest prospective natural history studies of DMD conducted to date, comprises more than 400 DMD patients with complete characterization of demographic data, along with assessments of clinical parameters affected by DMD. The three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (20 patients), all glucocorticoid-treated CINRG patients (172 patients), and all glucocorticoid-treated genotyped CINRG DNHS patients (148 patients). Approximately 13% of cases of DMD are amenable to exon 51 skipping therapies.

Patients in the global patient database experienced respiratory decline at rates in line with the well-established natural history of DMD. In contrast, the respiratory decline in patients treated with eteplirsen was significantly lower, and this was true across all stages of the disease evaluated. Specifically, both ambulatory and non-ambulatory patients demonstrated a slower rate of respiratory decline.

As the disease progresses, patients require increasing levels of clinical intervention including cough assist and ventilation support, and patients are at increased risk of death once this respiratory decline reaches a critical threshold. This work demonstrates that eteplirsen may slow the rate of respiratory decline and therefore may delay time to milestones of decline. This may have notable positive implications on quality of life, and because pulmonary decline is linked to mortality, slowing of decline may result in delayed mortality. The investigators acknowledge that longer term follow-up is needed.

Eteplirsen is an antisense oligonucleotide approved by the FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.


Full open access study: “Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy” by Navid Khan, Helen Eliopoulos, Lixin Han, T. Bernard Kinane, Linda P. Lowes, Jerry R. Mendell, Heather Gordish-Dressman, Erik K. Henricson, and Craig M. McDonald on behalf of the Eteplirsen Investigators and the CINRG DNHS Investigators (DOI: 10.3233/JND-180351), published in the Journal of Neuromuscular Diseases, Volume 6, Issue 2 (2019) by IOS Press. The article is openly available at:

Contact Diana Murray, IOS Press (+1 718-640-5678 or for additional information. Journalists who wish to interview the authors should contact Tracy Sorrentino, Corporate Affairs, Sarepta Therapeutics (+1 617-301-8566 or

These clinical trials were sponsored by Sarepta Therapeutics.

About the Journal of Neuromuscular Diseases
The Journal of Neuromuscular Diseases (JND) facilitates progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias, and myositis). JND publishes research reports, reviews, and short communications. Guided by Editors-in-Chief Carsten G. Bönnemann (National Institute of Neurological Disorders and Stroke, NIH) and Hanns Lochmüller (Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada), the journal is dedicated to providing an open forum for original research in basic science, translational, and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.

About IOS Press
IOS Press is headquartered in Amsterdam with satellite offices in the USA, Germany, India and China and serves the information needs of scientific and medical communities worldwide. IOS Press now publishes more than 80 international peer-reviewed journals and about 75 book titles each year on subjects ranging from computer science, artificial intelligence, and engineering to medicine, neuroscience, and cancer research.