{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:55:25Z","timestamp":1782932125737,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T00:00:00Z","timestamp":1596931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Lysosomal acid lipase deficiency is characterized by hepatomegaly and dyslipidaemia, which can lead to cirrhosis and premature atherosclerosis. Sebelipase alfa is an approved recombinant human lysosomal acid lipase. In an open\u2010label extension study of adults with lysosomal acid lipase deficiency (LAL\u2010CL04), sebelipase alfa treatment for 1\u00a0year reduced serum transaminase levels and liver fat content and improved serum lipid levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Final data from LAL\u2010CL04 are reported herein for patients who received sebelipase alfa infusions (1.0 or 3.0\u00a0mg\/kg every other week) for up to 5\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 8 patients enrolled, 7 received sebelipase alfa for 224\u2010260\u00a0weeks; 1 was lost to follow\u2010up. Median baseline levels of alanine aminotransferase and aspartate aminotransferase (81.5 and 50.0\u00a0U\/L, respectively) were decreased through the end\u2010of\u2010study visit (54.0 and 34.0\u00a0U\/L). Median low\u2010density lipoprotein cholesterol decreased from 113 to 78\u00a0mg\/dL, total cholesterol decreased from 171 to 132\u00a0mg\/dL, and high\u2010density lipoprotein cholesterol increased from 37 to 42\u00a0mg\/dL. Most treatment\u2010emergent adverse events were nonserious (99%), mild\/moderate (98%) and unrelated to sebelipase alfa (87%); no patient discontinued as a result of treatment\u2010emergent adverse events. One patient had 2 serious treatment\u2010emergent adverse events (cholecystitis and cholelithiasis; assessed as unlikely related to sebelipase alfa). Two patients had 20 nonserious infusion\u2010associated reactions in weeks 6\u201038; all were manageable. One patient tested positive for antidrug antibodies (single occurrence).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sebelipase alfa was well tolerated and improved serum transaminase and lipid levels for up to 5\u00a0years in adults with lysosomal acid lipase deficiency.<\/jats:p><jats:p><jats:bold>Trial registration number:<\/jats:bold> ClinicalTrials.gov record NCT01488097.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14603","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T09:27:19Z","timestamp":1594632439000},"page":"2203-2214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sebelipase alfa for lysosomal acid lipase deficiency: 5\u2010year treatment experience from a phase 2 open\u2010label extension study"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4415-0003","authenticated-orcid":false,"given":"V\u0115ra","family":"Malinov\u00e1","sequence":"first","affiliation":[{"name":"Department for Metabolic Diseases Children's Clinic General Faculty Hospital and First Faculty of Medicine of Charles University in Prague Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Balwani","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences and Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Medicine Salford Royal Foundation NHS Trust Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Baptiste","family":"Arnoux","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Diseases H\u00f4pital Necker\u2010Enfants Malades Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chester B.","family":"Whitley","sequence":"additional","affiliation":[{"name":"Advanced Therapies Program, and Gene Therapy Center University of Minnesota Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Marulkar","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Abel","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Metabolic and Molecular Bases of Inherited Disease","author":"Grabowski GA","year":"2012"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1509055"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.04.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.014"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.03.019"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.11.002"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.05.027"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000935"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)80092-X"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.12.036"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.03.010"},{"key":"e_1_2_11_13_1","volume-title":"Kanuma\u00ae (sebelipase alfa) [summary of product characteristics]","author":"Alexion Europe SAS","year":"2015"},{"key":"e_1_2_11_14_1","volume-title":"Kanuma\u00ae (sebelipase alfa) [package insert]","author":"Alexion Pharmaceuticals, Inc","year":"2015"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26289"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.022"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijsu.2014.07.013"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501365"},{"key":"e_1_2_11_19_1","first-page":"437A","article-title":"Long\u2010term benefit of sebelipase alfa over 96 weeks in a diverse population of children and adults with lysosomal acid lipase deficiency [abstract 817]","volume":"66","author":"Burton BK","year":"2017","journal-title":"Hepatology"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.14603","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14603","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14603","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14603","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T14:38:38Z","timestamp":1693924718000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,9]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/liv.14603"],"URL":"https:\/\/doi.org\/10.1111\/liv.14603","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,9]]},"assertion":[{"value":"2020-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}