{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:24:14Z","timestamp":1791944654283,"version":"4.3.4"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016814","name":"Marinus Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In the placebo\u2010controlled, double\u2010blind phase of the Marigold study (NCT03572933), ganaxolone significantly reduced major motor seizure frequency (MMSF) in patients with cyclin\u2010dependent kinase\u2010like 5 deficiency disorder (CDD). We report 2\u2010year safety and clinical outcomes data from the open\u2010label extension (OLE) phase of Marigold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with CDD who completed the double\u2010blind phase were eligible to continue in the OLE. Efficacy assessments included MMSF reduction from prerandomization baseline, responder rates, and Clinical Global Impression\u2013Improvement scores, including assessment of seizure intensity and duration (CGI\u2010CSID). Safety assessments included treatment\u2010emergent adverse events (TEAEs) and TEAEs leading to discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 101 patients who enrolled in Marigold, 88 (87.1%) entered the OLE (median age\u2009=\u20095\u2009years, 79.5% female). Median 28\u2010day MMSF at baseline was 50.6. At 2\u2009years in the OLE (months 22\u201324), MMSF was reduced by a median of 48.2% (<jats:italic>n<\/jats:italic>\u2009=\u200950); when missing data were imputed, median reduction in MMSF was 43.8% using a mixed effects model and 27.4% using a last observation carried forward model. During months 22\u201324, 23 of 50 (46.0%) patients experienced reductions in MMSF of \u226550%; 12 of 50 (24.0%) patients experienced MMSF reductions of \u226575%. During months 22\u201324, 40 of 49 (81.6%) patients were rated by caregivers as having improvement in seizure\u2010related outcomes based on CGI\u2010CSID scores. Thirty\u2010seven patients discontinued ganaxolone due to lack of efficacy (<jats:italic>n<\/jats:italic>\u2009=\u200913), withdrawal by caregiver (<jats:italic>n<\/jats:italic>\u2009=\u200912), adverse event (<jats:italic>n<\/jats:italic>\u2009=\u200910), physician decision (<jats:italic>n<\/jats:italic>\u2009=\u20091), or death (<jats:italic>n<\/jats:italic>\u2009=\u20091; unrelated to study drug). The most common treatment\u2010related TEAEs were somnolence (17.0%), seizure (11.4%), and decreased appetite (5.7%). Patients reported serious TEAEs (<jats:italic>n<\/jats:italic>\u2009=\u200928, 31.8%); those reported in \u22653% of patients were seizure (<jats:italic>n<\/jats:italic>\u2009=\u20096), pneumonia (<jats:italic>n<\/jats:italic>\u2009=\u20095), acute respiratory failure (<jats:italic>n<\/jats:italic>\u2009=\u20093), aspiration pneumonia (<jats:italic>n<\/jats:italic>\u2009=\u20093), and dehydration (<jats:italic>n<\/jats:italic>\u2009=\u20093).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Sustained reductions in MMSF at 2\u2009years in the OLE support the efficacy of ganaxolone in seizures associated with CDD. Safety findings in the OLE were consistent with the double\u2010blind phase.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17826","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T05:24:43Z","timestamp":1699680283000},"page":"37-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Long\u2010term treatment with ganaxolone for seizures associated with cyclin\u2010dependent kinase\u2010like 5 deficiency disorder: Two\u2010year open\u2010label extension follow\u2010up"],"prefix":"10.1111","volume":"65","author":[{"given":"Heather E.","family":"Olson","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Epilepsy and Clinical Neurophysiology Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Amin","sequence":"additional","affiliation":[{"name":"University Hospitals Bristol and Weston  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-0929","authenticated-orcid":false,"given":"Nadia","family":"Bahi\u2010Buisson","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Necker Enfants Malades University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"New York University Langone Comprehensive Epilepsy Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0902","authenticated-orcid":false,"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics University of Pennsylvania Perelman School of Medicine and Division of Neurology, Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-4167","authenticated-orcid":false,"given":"Elia","family":"Pestana\u2010Knight","sequence":"additional","affiliation":[{"name":"Epilepsy Center Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajsekar R.","family":"Rajaraman","sequence":"additional","affiliation":[{"name":"UCLA Mattel Children's Hospital  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8854-1773","authenticated-orcid":false,"given":"Alex A.","family":"Aimetti","sequence":"additional","affiliation":[{"name":"Marinus Pharmaceuticals, Inc.  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