{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:31:35Z","timestamp":1790994695826,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100031585","name":"Takeda Development Center Americas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031585","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study evaluated the efficacy, safety, and tolerability of soticlestat as adjunctive therapy in children and young adults with Dravet syndrome (DS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SKYLINE (NCT04940624) was a multicenter, randomized, double\u2010blind, placebo\u2010controlled, phase 3 trial that enrolled patients with DS aged 2\u201321\u2009years with uncontrolled convulsive seizures (\u22654\/month despite adequate treatment). Participants received oral soticlestat 300\u2009mg (weight adjusted) or matching placebo twice daily. The total study duration was 16\u2009weeks, comprising 4\u2010week dose titration and 12\u2010week maintenance treatment periods. The primary endpoint was a comparison of monthly convulsive seizure frequency between baseline and the titration\/maintenance periods. Key secondary endpoints included several modified Caregiver and Clinical Global Impression of Improvement (GI\u2010I) scales for DS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred forty\u2010four participants were randomized (71 placebo, 73 soticlestat) with a mean (SD) age of 10.3 (5.0) years; 72 (50%) were male, and 117 (81.3%) were receiving \u22653 antiseizure medications. Median change from baseline in convulsive seizure frequency over the full treatment period was \u22128.64% with placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200971) and \u221222.16% with soticlestat (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200973), a difference of \u221215.64% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.061); in the maintenance treatment period, these changes were \u221211.99% with placebo and \u221223.29% with soticlestat, a difference of \u221214.29% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.089). The proportion of participants with \u226550% reduction in convulsive seizures was 9.9% with placebo and 27.4% with soticlestat (nominal\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.008). Soticlestat showed clinically meaningful results in the Caregiver and Clinical GI\u2010I, and Clinical GI\u2010I Seizure Intensity and Duration scales over the 16\u2010week treatment period (all nominal\n                      <jats:italic>p<\/jats:italic>\n                      \u2010values\u2009\u2264\u2009.004). The most commonly reported treatment\u2010emergent adverse events related to study drug were somnolence, change in seizure presentation, decreased appetite, and insomnia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Although statistical significance was narrowly missed, soticlestat showed a numerical benefit over placebo for convulsive seizure decrease. Clinically meaningful benefits across multiple secondary endpoints were observed. No new safety concerns emerged.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70164","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:55:59Z","timestamp":1772992559000},"page":"2796-2807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Soticlestat as an adjunctive therapy in children and young adults with Dravet syndrome"],"prefix":"10.1002","volume":"67","author":[{"given":"Joseph","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California, San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-0809","authenticated-orcid":false,"given":"Kette","family":"Valente","sequence":"additional","affiliation":[{"name":"Departamento de Psiquiatria, Faculdade de Medicina Universidade de Sao Paulo  Sao Paulo 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