{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:55:17Z","timestamp":1791456917368,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational All"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Berotralstat (BCX7353) is an oral, once\u2010daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long\u2010term safety study of berotralstat in patients with HAE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>APeX\u2010S is an ongoing, phase 2, open\u2010label study conducted in 22 countries (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE\u2010C1\u2010INH) were centrally allocated to receive berotralstat 150\u00a0or 110\u00a0mg once daily. The primary objective was to determine long\u2010term safety and the secondary objective was to evaluate effectiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Enrolled patients (<jats:italic>N<\/jats:italic>\u00a0=\u00a0227) received berotralstat 150\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0127) or 110\u00a0mg (<jats:italic>n<\/jats:italic>\u00a0=\u00a0100) once daily. The median (range) duration of exposure was 342 (11\u2013540) and 307 (14\u2013429) days for the 150\u2010mg and 110\u2010mg groups, respectively. Treatment\u2010emergent adverse events (TEAEs) occurred in 91% (<jats:italic>n<\/jats:italic>\u00a0=\u00a0206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (<jats:italic>n<\/jats:italic>\u00a0=\u00a091, 40%), abdominal pain (<jats:italic>n<\/jats:italic>\u00a0=\u00a057, 25%), headache (<jats:italic>n<\/jats:italic>\u00a0=\u00a040, 18%), and diarrhea (<jats:italic>n<\/jats:italic>\u00a0=\u00a031, 14%) and were mostly mild to moderate. Fifty percent (<jats:italic>n<\/jats:italic>\u00a0=\u00a0113) of patients had at least one drug\u2010related adverse event (AE; 150\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a057 [45%]; 110\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a056 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a013 [10%]; 110\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a06 [6%]). Three (1.3%) patients experienced a drug\u2010related serious TEAE. Among patients who received berotralstat through 48\u00a0weeks (150\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a073; 110\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a030), median HAE attack rates were low in month 1 (150\u00a0mg, 1.0 attacks\/month; 110\u00a0mg, 0.5 attacks\/month) and remained low through 12\u00a0months (0 attacks\/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this analysis, both berotralstat doses, 150\u00a0 and 110\u00a0mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>The study is registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> (NCT03472040).<\/jats:p><\/jats:sec>","DOI":"10.1002\/clt2.12035","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T09:09:55Z","timestamp":1624007395000},"source":"Crossref","is-referenced-by-count":55,"title":["Long\u2010term safety and effectiveness of berotralstat for hereditary angioedema: The open\u2010label APeX\u2010S study"],"prefix":"10.1002","volume":"11","author":[{"given":"Henriette","family":"Farkas","sequence":"first","affiliation":[{"name":"Hungarian Angioedema Center of Reference and Excellence Department of Internal Medicine and Hematology Semmelweis University  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