{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:10:13Z","timestamp":1774354213193,"version":"3.50.1"},"reference-count":12,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The pivotal phase 3 trial MCI186\u201019 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval. Study 19 utilized a targeted enrollment enrichment strategy based on post hoc analyses from earlier trials, selecting patients with higher baseline function, more rapid disease progression, and better respiratory status. To evaluate the generalizability of Study 19 results, subsequent post hoc analyses assessed the efficacy of edaravone in broader ALS populations. One machine learning\u2010based analysis retrospectively applied a validated model to Study 16 data, stratifying patients by predicted risk of respiratory decline. This detectable effect cluster analysis suggested that up to 70% of Study 16 participants may have benefited from edaravone. A second analysis investigated edaravone efficacy in patients from Study 19 with forced vital capacity (FVC) &lt;\u200980% predicted (%p) at the start of treatment, since FVC \u2265\u200980%p was one of the Study 19 inclusion criteria. Both high\u2010 and low\u2010FVC subgroups demonstrated reduced ALS functional rating scale\u2010revised decline at 48\u2009weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations.<\/jats:p>","DOI":"10.1002\/mus.70042","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:29:44Z","timestamp":1770460184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generalizability of Edaravone Efficacy"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1914-5061","authenticated-orcid":false,"given":"Benjamin Rix","family":"Brooks","sequence":"first","affiliation":[{"name":"Clinical Trials Planning LLC  Charlotte North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Ennist","sequence":"additional","affiliation":[{"name":"Origent Data Sciences, Inc.  Vienna Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Beaulieu","sequence":"additional","affiliation":[{"name":"Origent Data Sciences, Inc.  Vienna Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3953","authenticated-orcid":false,"given":"Stephen","family":"Apple","sequence":"additional","affiliation":[{"name":"Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1599955"},{"issue":"1","key":"e_1_2_8_5_1","first-page":"47","article-title":"Edaravone in Amyotrophic Lateral Sclerosis\u2014Lessons From the Clinical Development Program and the Importance of a Strategic Clinical Trial Design","volume":"14","author":"Beydoun S. R.","year":"2018","journal-title":"US Neurology"},{"issue":"9","key":"e_1_2_8_6_1","first-page":"S175","article-title":"Edaravone in the Treatment of Amyotrophic Lateral Sclerosis: Efficacy and Access to Therapy\u2014A Roundtable Discussion","volume":"24","author":"Brooks B. 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