{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:50:40Z","timestamp":1789660240228,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR056973"],"award-info":[{"award-number":["R01AR056973"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014383","name":"Italfarmaco","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This ongoing, open\u2010label extension study is evaluating the long\u2010term safety, tolerability, and efficacy of givinostat, a Class I and II histone deacetylase inhibitor, in patients with Duchenne muscular dystrophy (DMD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The recruited patients completed one of two prior clinical studies (one Phase 2 and one Phase 3 [EPIDYS]), receiving givinostat or placebo, or were successfully screened but not randomized into EPIDYS. All receive givinostat oral suspension open\u2010label at a flexible, weight\u2010based dose in addition to systemic corticosteroids, and attend visits every 4\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 194 patients are included in the current analyses, with a mean duration of givinostat exposure (excluding use in prior studies) of 559.6\u2009days (SD 373.0); when including use in the prior studies, the maximum exposure to givinostat was &gt;\u20098\u2009years. Although the majority of patients reported \u2265\u20091 adverse event (169\/194 [87.1%]), most were mild\/moderate in severity, and the safety profile of givinostat was consistent with prior studies. Post hoc comparisons with natural history datasets (ImagingDMD and CINRG) suggest, in propensity matched populations, givinostat added to systemic corticosteroids significantly delayed the loss of the ability to rise from the floor, the loss of the ability to complete the 4\u2010stair climb test, and the loss of ambulation (by medians of 2.0\u20133.3\u2009years; all nominal\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Overall, the safety and tolerability of long\u2010term administration of givinostat in patients with DMD was consistent with previous studies. Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      EudraCT number: 2017\u2010000397\u201010;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT03373968\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70165","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T04:14:40Z","timestamp":1755663280000},"page":"2335-2348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Long\u2010Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons"],"prefix":"10.1002","volume":"12","author":[{"given":"Craig M.","family":"McDonald","sequence":"first","affiliation":[{"name":"University of California Davis Health  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Guglieri","sequence":"additional","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragana","family":"Vu\u010dini\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Neurology and Psychiatry for Children and Youth  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyula","family":"Acsadi","sequence":"additional","affiliation":[{"name":"Division of Neurology Connecticut Children's  Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Brandsema","sequence":"additional","affiliation":[{"name":"Division of Neurology The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Bruno","sequence":"additional","affiliation":[{"name":"Center of Translational and Experimental Myology IRCCS Istituto Giannina Gaslini  Genova Italy"},{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health \u2013 DINOGMI University of Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika L.","family":"Finanger","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children \u2013 Portland  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Harper","sequence":"additional","affiliation":[{"name":"Division of Neurology Virginia Commonwealth University, Children's Hospital of Richmond  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes Lopez","family":"Lobato","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Rocio  Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Masson","sequence":"additional","affiliation":[{"name":"Developmental Neurology Unit Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Muelas","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Neurology Department Hospital Universitari i Polit\u00e8cnic La Fe  Valencia Spain"},{"name":"Neuromuscular Reference Centre, European Reference Network for Neuromuscular Diseases (ERN\u2010EURO\u2010NMD), Neuromuscular and Ataxias Research Group Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia 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Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Phan","sequence":"additional","affiliation":[{"name":"MD Rare Disease Research, LLC  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria A.","family":"Sansone","sequence":"additional","affiliation":[{"name":"Neurorehabilitation Unit, The NeMO Clinical Center in Milan University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariacristina","family":"Scoto","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre and MRC Centre for NMD Great Ormond Street Hospital &amp; UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Willis","sequence":"additional","affiliation":[{"name":"The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust  Oswestry 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