{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:02:42Z","timestamp":1793646162097,"version":"4.5.1"},"reference-count":18,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:p>Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of\u200a&gt;\u200a4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]). Objective: To evaluate the efficacy and safety of viltolarsen for an additional 192 weeks in boys with DMD. Methods: This phase 2, open-label, 192-week long-term extension (LTE) study (NCT03167255) evaluated the efficacy and safety of viltolarsen in participants aged 4 to\u200a&lt;\u200a10 years at baseline with DMD amenable to exon 53 skipping. All 16 participants from the initial 24-week study enrolled into this LTE. Timed function tests were compared to the CINRG DNHS group. All participants received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine (TTSTAND). Secondary efficacy outcomes included additional timed function tests. Safety was continuously assessed. Results: For the primary efficacy outcome (TTSTAND), viltolarsen-treated patients showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years compared with the CINRG DNHS control group which declined. Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate. No participants discontinued drug during the study. Conclusions: Based on the results of this 4-year LTE, viltolarsen can be an important treatment strategy for DMD patients amenable to exon 53 skipping.<\/jats:p>","DOI":"10.3233\/jnd-221656","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T11:59:24Z","timestamp":1680263964000},"page":"439-447","source":"Crossref","is-referenced-by-count":42,"title":["Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study"],"prefix":"10.1177","volume":"10","author":[{"given":"Paula R.","family":"Clemens","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CINRG DNHS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamshi K.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Neurology, Ann and Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Division of Neurology, Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Harper","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at Virginia Common wealth University, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean K.","family":"Mah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Department of Pediatrics, UC Davis Health, University of California, Davis, Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University Medical Center, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"Zaidman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University at St Louis, St Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"NS Pharma, Inc., Paramus, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Binghamton University \u2013 State University of New York, Binghamton, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/JND-221656_ref1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul Disord"},{"issue":"4","key":"10.3233\/JND-221656_ref2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD Global Database: Analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","author":"Bladen","year":"2015","journal-title":"Hum Mutat"},{"issue":"6","key":"10.3233\/JND-221656_ref3","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: The protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"issue":"2","key":"10.3233\/JND-221656_ref4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S1474-4422(09)70272-8","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part Implementation of multidisciplinary care","volume":"9","author":"Bushby","year":"2010","journal-title":"Lancet Neurol"},{"key":"10.3233\/JND-221656_ref5","doi-asserted-by":"crossref","unstructured":"Wilton-Clark H , Yokota T . Antisense and gene therapy options for Duchenne muscular dystrophy arising from mutations in the N-terminal hotspot. Genes (Basel). 2022;13(2).","DOI":"10.3390\/genes13020257"},{"issue":"9","key":"10.3233\/JND-221656_ref6","doi-asserted-by":"crossref","first-page":"e2112546119","DOI":"10.1073\/pnas.2112546119","article-title":"Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy","volume":"119","author":"Lim","year":"2022","journal-title":"Proc Natl Acad Sci"},{"key":"10.3233\/JND-221656_ref7","doi-asserted-by":"crossref","unstructured":"Eser G , Topaloglu H . Current outline of exon skipping trials in Duchenne muscular dystrophy. Genes (Basel). 2022;13(7).","DOI":"10.3390\/genes13071241"},{"issue":"4","key":"10.3233\/JND-221656_ref8","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1756285615586123","article-title":"Duchenne muscular dystrophy: Current cell therapies","volume":"8","author":"Sienkiewicz","year":"2015","journal-title":"Ther Adv Neurol Disord"},{"issue":"1","key":"10.3233\/JND-221656_ref9","first-page":"54","article-title":"Exploring the molecular basis for variability among patients with Becker muscular dystrophy: Dystrophin gene and protein studies","volume":"49","author":"Beggs","year":"1991","journal-title":"Am J Hum Genet"},{"issue":"4","key":"10.3233\/JND-221656_ref10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3233\/JND-220811","article-title":"Long-term functional efficacy and safety of viltolarsen in patients with Duchenne muscular dystrophy","volume":"9","author":"Clemens","year":"2022","journal-title":"J Neuromuscul Dis"},{"issue":"7","key":"10.3233\/JND-221656_ref11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41582-019-0203-3","article-title":"Therapeutic developments for Duchenne muscular dystrophy","volume":"15","author":"Verhaart","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JND-221656_ref12","doi-asserted-by":"crossref","unstructured":"Komaki H , Nagata T , Saito T , Masuda S , Takeshita E , Sasaki M , et al. Systemic administration of the antisense oligonucleotide NS-065\/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci Transl Med. 2018;10(437).","DOI":"10.1126\/scitranslmed.aan0713"},{"issue":"8","key":"10.3233\/JND-221656_ref13","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","article-title":"Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping: A phase 2 randomized clinical trial","volume":"77","author":"Clemens","year":"2020","journal-title":"JAMA Neurol"},{"key":"10.3233\/JND-221656_ref15","unstructured":"Viltolarsen (JAN*). Pharmaceutical Evaluation Division, Pharmaceutical Safety and Environmental Health Bureau; Ministry of Health, Labour andWelfare. In: PMDA, editor. 2019."},{"issue":"5","key":"10.3233\/JND-221656_ref16","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/mus.26334","article-title":"Timed function tests have withstood the test of time as clinically meaningful and responsive endpoints in Duchenne muscular dystrophy","volume":"58","author":"McDonald","year":"2018","journal-title":"Muscle Nerve"},{"issue":"1","key":"10.3233\/JND-221656_ref17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/nat.2021.0043","article-title":"Long-term safety and efficacy data of golodirsen in ambulatory patients with Duchenne muscular dystrophy amenable to exon 53 skipping: A first-in-human, multicenter, two-part, open-label, phase 1\/2 trial","volume":"32","author":"Servais","year":"2022","journal-title":"Nucleic Acid Ther"},{"issue":"2","key":"10.3233\/JND-221656_ref18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann Neurol"},{"issue":"15","key":"10.3233\/JND-221656_ref19","doi-asserted-by":"crossref","first-page":"e1540","DOI":"10.1212\/WNL.0000000000201626","article-title":"DMD genotypes and motor function in Duchenne muscular dystrophy: a multi-institution meta-analysis with implications for clinical trials","volume":"100","author":"Muntoni","year":"2023","journal-title":"Neurology"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-221656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:52:25Z","timestamp":1777506745000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-221656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,2]]},"references-count":18,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3233\/jnd-221656","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,2]]}}}