{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:14Z","timestamp":1786978514786,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Evinacumab, an angiopoietin\u2010like 3 inhibitor, significantly reduces low\u2010density lipoprotein cholesterol (LDL\u2010C) in patients with homozygous familial hypercholesterolemia (HoFH). Herein, we report pharmacokinetic and efficacy analyses of evinacumab in &lt;\u20095\u2010year\u2010old patients with HoFH. Population pharmacometric models characterizing evinacumab exposure and LDL\u2010C response accounting for lipoprotein apheresis effect in \u2265\u20095\u2010year\u2010old patients were adapted for growth and maturation to predict and compare evinacumab and LDL\u2010C concentrations across age\/weight groups in virtual \u2265\u20096\u2010month\u2010old patients receiving 15\u2009mg\/kg evinacumab intravenous (iv) infusions every 4\u2009weeks (q4w). As expected from allometric theory, weight\u2010based dosing resulted in decreasing evinacumab exposures with declining body weight. Consistent with trends observed in &gt;\u20095\u2010year\u2010old patients, the predicted percent change from LDL\u2010C baseline (%\u2206LDL\u2010C) was generally comparable or even higher in &lt;\u20095\u2010year\u2010old patients (63.0%\u201368.5%) than in 5\u2010 to &lt;\u200918\u2010year\u2010old patients (61.3%\u201367.8%) or adults (51.7%), with the predicted percentages of patients achieving %\u2206LDL\u2010C\u2009&gt;\u200950% also higher in &lt;\u20095\u2010year\u2010old patients (82.0%\u201386.9%) versus 5\u2010 to &lt;\u200918\u2010year\u2010old patients (72.0%\u201384.5%) and adults (54.8%). Through a managed access program, six 1\u2010 to &lt;\u20095\u2010year\u2010old patients received between 5 and 23 iv infusions of 15\u2009mg\/kg evinacumab q4w. Rapid and clinically meaningful LDL\u2010C reductions were observed, with %\u2206LDL\u2010C at the last reported dose ranging from 41.3% to 77.3%. Based on the actual patient dosing and plasmapheresis history, model\u2010predicted evinacumab and LDL\u2010C concentrations were comparable to the observed data collected in the managed access program. Overall, this analysis provides evidence for the use of evinacumab 15\u2009mg\/kg iv q4w dosing regimen in 6\u2010month\u2010old to 5\u2010year\u2010old patients.<\/jats:p>","DOI":"10.1002\/psp4.70017","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T09:34:56Z","timestamp":1742204096000},"page":"1835-1847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparison of Model\u2010Predicted and Observed Evinacumab Pharmacokinetics and Efficacy in Children Aged &lt;\u20095\u2009Years With Homozygous Familial Hypercholesterolemia"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2326-3335","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Bihorel","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-8555","authenticated-orcid":false,"given":"Robert","family":"Dingman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Mendell","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8841-0212","authenticated-orcid":false,"given":"Katy C.","family":"Norman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4817-0378","authenticated-orcid":false,"given":"Richard T.","family":"George","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Qiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1243-424X","authenticated-orcid":false,"given":"Daniel","family":"Garcia","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical, Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7695-3498","authenticated-orcid":false,"given":"Wendy S.","family":"Putnam","sequence":"additional","affiliation":[{"name":"Ultragenyx Pharmaceutical, Inc.  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Raghuveer","sequence":"additional","affiliation":[{"name":"University of Missouri\u2010Kansas City School of Medicine Children's Mercy Hospital  Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6485-6551","authenticated-orcid":false,"given":"Brian W.","family":"McCrindle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Toronto, Labatt Family Heart Centre, the Hospital for Sick Children  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-3773","authenticated-orcid":false,"given":"Elena","family":"Fornari","sequence":"additional","affiliation":[{"name":"Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5119-9174","authenticated-orcid":false,"given":"Ivo","family":"Baric","sequence":"additional","affiliation":[{"name":"Department of Paediatrics University Hospital Centre Zagreb and University of Zagreb, School of Medicine  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-4502","authenticated-orcid":false,"given":"Shubha","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology and Diabetes Children's Hospital at Westmead  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9033-0959","authenticated-orcid":false,"given":"Melissa","family":"Diamond","sequence":"additional","affiliation":[{"name":"Joe DiMaggio Children's Hospital Memorial Division of Pediatric Cardiology  Hollywood Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-4010","authenticated-orcid":false,"given":"Eliot A.","family":"Brinton","sequence":"additional","affiliation":[{"name":"Utah Lipid Center  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Davis","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Thomas","family":"DiCioccio","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-1577","authenticated-orcid":false,"given":"Lutz","family":"Harnisch","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc.  Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323896111"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324022111"},{"key":"e_1_2_10_4_1","unstructured":"Center for Drug Evaluation and Research \u201cPharmacology\/Toxicology NDA\/BLA Review and Evaluation. 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