{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:11:06Z","timestamp":1792440666361,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is caused by mutations in the <jats:italic>DMD<\/jats:italic> gene resulting in the absence of dystrophin. Casimersen is a phosphorodiamidate morpholino oligomer designed to bypass frameshift <jats:italic>DMD<\/jats:italic> mutations and produce internally truncated, yet functional, dystrophin protein in patients amenable to exon 45 skipping. Our primary study objective was to evaluate safety and tolerability of casimersen; the secondary objective was to characterize the plasma pharmacokinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter, phase 1\/2 trial enrolled 12 participants (aged 7\u201021\u2009years, who had limited ambulation or were nonambulatory) and comprised a 12\u2010week, double\u2010blind dose titration, then an open\u2010label extension for up to 132\u2009weeks. During dose titration, participants were randomized 2:1 to weekly casimersen infusions at escalating doses of 4, 10, 20, and 30\u2009mg\/kg (\u22652\u2009weeks per dose), or placebo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Participants received casimersen for a mean 139.6\u2009weeks. Treatment\u2010emergent adverse events (TEAEs) occurred in all casimersen\u2010 and placebo\u2010treated participants and were mostly mild (over 91.4%) and unrelated to casimersen or its dose. There were no deaths, dose reductions, abnormalities in laboratory parameters or vital signs, or casimersen\u2010related serious AEs. Casimersen plasma concentration increased with dose and declined similarly for all dose levels over 24\u2009hours postinfusion. All pharmacokinetic parameters were similar at weeks 7 and 60.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Casimersen was well tolerated in participants with DMD amenable to exon 45 skipping. Most TEAEs were mild, nonserious, and unrelated to casimersen. Plasma exposure was dose proportional with no suggestion of plasma accumulation. These results support further studies of casimersen in this population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27347","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T03:24:23Z","timestamp":1623209063000},"page":"285-292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":158,"title":["Safety, tolerability, and pharmacokinetics of casimersen in patients with <scp>D<\/scp>uchenne muscular dystrophy amenable to exon <scp>45<\/scp> skipping: A randomized, double\u2010blind, placebo\u2010controlled, dose\u2010titration trial"],"prefix":"10.1002","volume":"64","author":[{"given":"Kathryn R.","family":"Wagner","sequence":"first","affiliation":[{"name":"Center for Genetic Muscle Disorders Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Departments of Neurology and Neuroscience Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Ann &amp; Robert H. Lurie Children's Hospital  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Koenig","sequence":"additional","affiliation":[{"name":"Clinical Development, Sarepta Therapeutics, Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"East","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Sarepta Therapeutics, Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Upadhyay","sequence":"additional","affiliation":[{"name":"Pharmacovigilance, Sarepta Therapeutics, Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoguang","family":"Han","sequence":"additional","affiliation":[{"name":"Biostatistics, Sarepta Therapeutics, Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7145-7663","authenticated-orcid":false,"given":"Perry B.","family":"Shieh","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California, Los Angeles  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01430-8"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S93873"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60756-3"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S97635"},{"key":"e_1_2_12_6_1","unstructured":"Sarepta Therapeutics Inc.Exondys\u00ae (eteplirsen) injection for intravenous use. US prescribing information.2020."},{"key":"e_1_2_12_7_1","unstructured":"Sarepta Therapeutics Inc.Vyondys\u00ae (golodirsen) injection for intravenous use. US prescribing information.2021."},{"key":"e_1_2_12_8_1","unstructured":"NS Pharma Inc.Viltepso\u00ae (viltolarsen) injection for intravenous use. US prescribing information.2021."},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1264"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009233"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01267-2"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23982"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015858"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24555"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-170272"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-180351"},{"key":"e_1_2_12_17_1","unstructured":"MuntoniF ServaisL StraubV et al.Long\u2010term safety and efficacy of golodirsen in male patients with Duchenne muscular dystrophy amenable to exon 53 skipping. Muscular Dystrophy Association Virtual Conference Hub;2020. https:\/\/mdaconference.org\/index.php\/node\/936"},{"key":"e_1_2_12_18_1","unstructured":"Sarepta Therapeutics Inc.Amondys 45 (casimersen) injection for intravenous use. US prescribing information.2021."},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20918"},{"key":"e_1_2_12_20_1","volume":"14","author":"Brogna C","year":"2019","journal-title":"PLoS One"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002891"},{"key":"e_1_2_12_22_1","volume":"16","author":"Zhang S","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2015.0598"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51235"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.27347","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.27347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T17:08:27Z","timestamp":1692983307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.27347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/mus.27347"],"URL":"https:\/\/doi.org\/10.1002\/mus.27347","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]},"assertion":[{"value":"2020-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}