{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:01:37Z","timestamp":1792879297786,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This randomized, double\u2010blind, phase 1b\/2a clinical trial was designed to evaluate the safety, tolerability, and efficacy of oral bexicaserin versus placebo for the treatment of seizures in adolescents and adults with developmental and epileptic encephalopathies (DEEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible participants had a DEE diagnosis, were aged 12\u201365\u2009years, and were taking 1\u20134 concomitant antiseizure medications. Randomization to treatment groups (4:1 bexicaserin:placebo) was stratified by type of DEE (Dravet syndrome [DS], Lennox\u2013Gastaut syndrome [LGS], or DEE Other). Following a 28\u2010day baseline period, the treatment period consisted of a 15\u2010day flexible uptitration period (6, 9, or 12\u2009mg three times daily, 5\u2009days each) and a 60\u2010day maintenance period on the highest tolerated dose. Primary end points were safety (adverse events) and change from baseline in countable motor seizure frequency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty\u2010three and nine participants were assigned to bexicaserin treatment and placebo, respectively, and received \u22651 dose (safety set); 35 bexicaserin and nine placebo participants completed titration, entered the maintenance period, and had \u22651 seizure measurement during the maintenance period (full analysis set). Twenty\u2010eight of 43 bexicaserin\u2010treated participants (65.1%) and three of nine (33.3%) in the placebo group reported drug\u2010related treatment\u2010emergent adverse events (TEAEs); seven of 43 participants (16.3%) discontinued bexicaserin due to a TEAE during titration and two of 43 (4.7%) during maintenance, most frequently due to somnolence. Median reductions in countable motor seizure frequencies were \u221259.8% with bexicaserin and \u221217.4% with placebo; reductions with bexicaserin were observed across DEEs (DS, \u221274.6%; LGS, \u221250.8%; DEE Other, \u221265.5%). The proportion of participants achieving \u226550% reductions during the treatment period (responder analysis) was 60.0% with bexicaserin versus 33.3% with placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Bexicaserin was well tolerated and associated with clinically relevant reductions in countable motor seizure frequencies in participants with a variety of DEEs. This novel trial design may expand treatment access to patients previously excluded from clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18689","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T12:03:32Z","timestamp":1761307412000},"page":"646-659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Bexicaserin for the treatment of seizures in developmental and epileptic encephalopathies: A phase 1b\/2a trial (\n                    <scp>PACIFIC<\/scp>\n                    )"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3088-7645","authenticated-orcid":false,"given":"Dennis J.","family":"Dlugos","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Epilepsy Research Centre University of Melbourne, Austin Health  Heidelberg Victoria Australia"},{"name":"Department of Paediatrics Royal Children's Hospital, University of Melbourne  Parkville Victoria Australia"},{"name":"Florey Institute of Neuroscience and Mental Health and Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2242-8027","authenticated-orcid":false,"given":"Jacqueline A.","family":"French","sequence":"additional","affiliation":[{"name":"New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-0537","authenticated-orcid":false,"given":"David G.","family":"Vossler","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4220-2508","authenticated-orcid":false,"given":"Chad","family":"Orevillo","sequence":"additional","affiliation":[{"name":"Longboard Pharmaceuticals (now part of H. Lundbeck A\/S)  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7680-4789","authenticated-orcid":false,"given":"Shikha","family":"Polega","sequence":"additional","affiliation":[{"name":"H. Lundbeck A\/S  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-7287","authenticated-orcid":false,"given":"Randall","family":"Kaye","sequence":"additional","affiliation":[{"name":"Longboard Pharmaceuticals (now part of H. Lundbeck A\/S)  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"and the LP352\u2010201 Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00546-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00063.2021"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18265"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17239"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17547"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15187"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207080"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2021.1244"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108324"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003685"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562864231191000"},{"key":"e_1_2_10_15_1","unstructured":"VosslerDG GidalBE.A summary of antiseizure medications available in the United States: 4th Edition. 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