{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:59:33Z","timestamp":1787968773980,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To report interim data from an ongoing, open\u2010label extension (OLE) of a Phase 2b study (X\u2010TOLE) of azetukalner in adults with focal onset seizures (FOS) receiving 1\u20133\u2009antiseizure medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible participants enrolled in the 7\u2010year OLE at 20\u2009mg azetukalner once daily with food. Long\u2010term seizure outcomes included median percentage change (MPC) in monthly (28\u2009days) FOS frequency from the double\u2010blind phase (DBP) baseline and achievement of \u226550%, \u226575%, \u226590%, and 100% seizure reductions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>285\u2009participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At the 24\u2010month interim analysis (September 5, 2023), 182 participants had been treated for \u226512\u2009months and 165 for \u226524\u2009months; 152 (55.3%) continued in the study. The median (range) treatment duration in the OLE was 26.3 (0.1\u201346.6) months. MPC reduction was 83.2% at 24\u2009months in the OLE vs. DBP baseline. For all participants who entered the OLE, 56.4% (155\/275) and 44.4% (122\/275) achieved a \u226550% seizure reduction, 28.4% (78\/275) and 19.6% (54\/275) achieved a \u226590% seizure reduction, and 22.2% (61\/275) and 14.9% (41\/275) achieved seizure freedom (100% seizure reduction) for any consecutive \u22656\u2010 and \u226512\u2010month period, respectively. For those who reached \u226524\u2009months in the OLE, seizure freedom was achieved by 34.5% (57\/165) and 23.6% (39\/165) for any consecutive \u22656\u2010 and \u226512\u2010month period, respectively. The majority of treatment\u2010emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were dizziness (21.8%), headache (15.3%), coronavirus infection (15.3%), somnolence (12.7%), fall (12.7%), and memory impairment (10.9%). Serious AEs were reported in 35 (12.7%) participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The efficacy demonstrated by azetukalner in reducing FOS seizure frequency in the DBP was sustained in this interim analysis. Azetukalner was generally well tolerated, with no new safety signals compared to the DBP. These data suggest sustained long\u2010term efficacy and safety of azetukalner in a difficult\u2010to\u2010treat population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>This long\u2010term study assessed the safety and efficacy of azetukalner to treat focal seizures. Patients taking azetukalner daily with food for about 2\u2009years had far fewer focal seizures with azetukalner than before taking the medication. For those who had been treated for 24\u2009months, about a third were seizure\u2010free for a consecutive 6\u2010month period, and about a quarter were seizure\u2010free for a consecutive 12\u2010month period. Most side effects were mild or moderate, and these included dizziness, headache, and somnolence (sleepiness).<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.70015","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:57:36Z","timestamp":1741741056000},"page":"539-548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interim analysis of the long\u2010term efficacy and safety of azetukalner in an ongoing open\u2010label extension study following a phase 2b clinical trial (X\u2010<scp>TOLE<\/scp>) in adults with focal epilepsy"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline A.","family":"French","sequence":"first","affiliation":[{"name":"New York University Comprehensive Epilepsy Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Porter","sequence":"additional","affiliation":[{"name":"University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Neuroscience Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-2892","authenticated-orcid":false,"given":"Martin J.","family":"Brodie","sequence":"additional","affiliation":[{"name":"University Department of Medicine and Therapeutics Western Infirmary  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3296-8193","authenticated-orcid":false,"given":"Michael A.","family":"Rogawski","sequence":"additional","affiliation":[{"name":"School of Medicine University of California, Davis  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Harden","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals Inc.  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Qian","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals Inc.  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza Luzon","family":"Rosenblut","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals Inc.  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kenney","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals Inc.  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory N.","family":"Beatch","sequence":"additional","affiliation":[{"name":"Xenon Pharmaceuticals Inc.  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"X\u2010TOLE Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052912"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2359-y"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107966"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.1908263"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115413"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527322666221227112621"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3542"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18056"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17376"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14557"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16725"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50896"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13670"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000200792"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14044"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17223"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03441.x"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T06:11:24Z","timestamp":1745388684000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/epi4.70015"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70015","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,7]]},"assertion":[{"value":"2024-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}