{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:25:53Z","timestamp":1789820753227,"version":"4.0.1"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,1,30]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The phase 3, part B, open-label study treated 14 patients 5 to 11 years of age with genetically proven HoFH (true homozygotes and compound heterozygotes) with LDL-C &gt;130 mg\/dL, despite optimized lipid-lowering therapy (including LDLR-independent apheresis and lomitapide), with intravenous evinacumab 15 mg\/kg every 4 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Evinacumab treatment rapidly and durably (through week 24) decreased LDL-C with profound reduction in the first week, with a mean (SE) LDL-C reduction of \u221248.3% (10.4%) from baseline to week 24. ApoB (mean [SE], \u201341.3% [9.0%]), non\u2013high-density lipoprotein cholesterol (\u201348.9% [9.8%]), and total cholesterol (\u201349.1% [8.1%]) were similarly decreased. Treatment-emergent adverse events were reported in 10 (71.4%) patients; however, only 2 (14.3%) reported events that were considered to be treatment-related (nausea and abdominal pain). One serious treatment-emergent adverse event of tonsillitis occurred (n=1), but this was not considered treatment-related.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Evinacumab constitutes a new treatment for pediatric patients with HoFH and inadequately controlled LDL-C despite optimized lipid-lowering therapy, lowering LDL-C levels by nearly half in these extremely high-risk and difficult-to-treat individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT04233918.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.123.065529","type":"journal-article","created":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T05:00:45Z","timestamp":1697778045000},"page":"343-353","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":92,"title":["Evinacumab for Pediatric Patients With Homozygous Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"149","clinical-trial-number":[{"clinical-trial-number":"nct04233918","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5671","authenticated-orcid":true,"given":"Albert","family":"Wiegman","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Amsterdam University Medical Centers, Location University of Amsterdam, The Netherlands (A.W., M.D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-8370","authenticated-orcid":true,"given":"Susanne","family":"Greber-Platzer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Austria (S.G.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazia","family":"Ali","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY (S.A., J.M., S.B., P.B., R.T.G., B.H., R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-1936","authenticated-orcid":true,"given":"M. Doortje","family":"Reijman","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Amsterdam University Medical Centers, Location University of Amsterdam, The Netherlands (A.W., M.D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-4010","authenticated-orcid":true,"given":"Eliot A","family":"Brinton","sequence":"additional","affiliation":[{"name":"Utah Lipid Center, Salt Lake City (E.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-9026","authenticated-orcid":true,"given":"Min-Ji","family":"Charng","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (M.-J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubha","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Diabetes, 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