{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:59:34Z","timestamp":1787968774671,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006546","name":"Angelini Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Investigate real\u2010world outcomes in drug\u2010resistant epilepsy (DRE) patients treated with cenobamate as adjunctive treatment to other antiseizure medications (ASMs) within the Early Access Programs (EAP) in Germany, France, and the United Kingdom.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DRE adults with uncontrolled focal\u2010onset seizures were included from 19 hospitals participating in the EAP in this retrospective study. Data were sourced from clinical records. Participants were evaluated at baseline, 1 months, and 3\u2009months from cenobamate start, and 3, 6, and 12\u2009months after maintenance. The primary effectiveness endpoint was the 50% responder rate, defined as the reduction in seizure frequency \u226550%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Data were collected from 298 patients who received at least one dose of cenobamate; efficacy was evaluated on 216 patients with seizure data available. At baseline, the median epilepsy duration was 22.2\u2009years, and 41.9% of patients had previous epilepsy surgery, including vagus nerve stimulation, with a median of nine previously failed ASMs. The median number of seizures\/month was 8.8. After 3\u2009months of maintenance, the 50% responder rate (primary endpoint) was 49.3%; the median percentage seizure reduction from baseline was 49.1%. A total of 100%, \u226590%, and \u226575% seizures reduction were reported in 13.6%, 20.0%, and 33.6% of patients, respectively. Both the responder rate and the median percentage seizure reduction steadily increased during the observation period. At 6\u2010month maintenance, the seizure\u2010free rate was 24.2%. The retention rate assessed by Kaplan\u2013Meier decreased from 96.6% at 1\u2010month cenobamate start to 69.7% at 12\u2010month maintenance. Adverse Drug Reactions (ADRs) to cenobamate occurred in 30.9% of patients, with asthenia, dizziness, and somnolence being the most frequent; the majority were mild\u2010to\u2010moderate and resolved during the observation period; three patients (1.0%) experienced a total of seven serious ADRs, all during titration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>In this study, cenobamate demonstrated to be an effective option for people with uncontrolled epilepsy even after multiple failed ASMs or failure of epilepsy surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>This study involved patients with drug\u2010resistant epilepsy, who had continued seizures despite using at least two antiseizure medications (ASMs). Patients received cenobamate (Ontozry) as epilepsy treatment during the Early Access Program (EAP) in France, Germany, and the United Kingdom. An EAP allows patients to receive promising new drugs under clinical supervision before they are commercially available. After 6\u2009months from cenobamate start, 49.3% of patients had their seizures cut by half or more, and 13.6% became seizure\u2010free. A total of 30.9% of patients had an undesirable reaction to cenobamate, mostly mild\u2010to\u2010moderate and resolved; the most frequent were asthenia, dizziness, and somnolence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70021","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T13:32:50Z","timestamp":1742736770000},"page":"736-748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Real\u2010world effectiveness and tolerability of cenobamate in drug\u2010resistant epilepsy: A retrospective analysis of the patients included into the Early Access Programs (\n                    <scp>EAP<\/scp>\n                    ) in Germany, France, and\n                    <scp>United Kingdom<\/scp>"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-8515","authenticated-orcid":false,"given":"Sylvain","family":"Rheims","sequence":"first","affiliation":[{"name":"Department of Functional Neurology and Epileptology Hospices Civils de Lyon and Lyon 1 University  Lyon France"},{"name":"Lyon's Neuroscience Research Center, INSERM U1028\/CNRS UMR 5292, Lyon 1 University  Lyon France"},{"name":"Epilepsy Institute  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-5862","authenticated-orcid":false,"given":"Bernhard J.","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"Department for Adults Kork Epilepsy Center  Kehl\u2010Kork Germany"},{"name":"Medical Faculty University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0833-8850","authenticated-orcid":false,"given":"Edouard","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Francis Rohmer Neurology Epilepsy Units, National Institute of Health and Medical Research 1258, Federation of Translational Medicine of Strasbourg Strasbourg University  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Rosenow","sequence":"additional","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Center of Neurology and Neurosurgery, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"LOEWE Center for Personalized Translational Epilepsy Research (CePTER) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Biraben","sequence":"additional","affiliation":[{"name":"Epilepsy Unit, Neurology Department CHU Pontchaillou  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-8623","authenticated-orcid":false,"given":"Rhys","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal Victoria Infirmary  Newcastle Upon Tyne UK"},{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5802-6226","authenticated-orcid":false,"given":"Alessandro","family":"Lovera","sequence":"additional","affiliation":[{"name":"Global Medical Department Angelini Pharma S.p.A  Rome 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S.p.A  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthinathan","family":"Thangavelu","sequence":"additional","affiliation":[{"name":"Statistics Department Medastats, LLC  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Global Medical Department Angelini Pharma S.p.A  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252807.38124.a3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000503831"},{"key":"e_1_2_12_4_1","unstructured":"Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY\u2010NC\u2010SA 3.0 IGO."},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.3949"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12560"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.05.031"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13723"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30035-1"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.120.019539"},{"key":"e_1_2_12_11_1","unstructured":"Xcorpi FDA. [Accessed 2021 May 1]. Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/212839s000lbl.pdf"},{"key":"e_1_2_12_12_1","unstructured":"Ontozry EMA EPAR. Available from:https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ontozry"},{"key":"e_1_2_12_13_1","unstructured":"Ontozry EMA. 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