{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:21:02Z","timestamp":1793262062101,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis Pharma AG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Inclisiran is a small interfering RNA molecule that reduces low-density lipoprotein cholesterol (LDL-C) by inhibition of proprotein convertase subtilisin\/kexin type 9. This subcutaneous, twice-yearly administered agent has been shown to effectively and safely lower LDL-C in adult patients with established atherosclerotic cardiovascular disease, adults at high risk for atherosclerotic cardiovascular disease, as well as in adults with heterozygous familial hypercholesterolaemia. With the current, limited treatment options available to reach treatment goals in children with severe heterozygous familial hypercholesterolaemia, homozygous familial hypercholesterolaemia, or statin intolerance, inclisiran could be a valuable new therapeutic option.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The objective of these ongoing studies is to investigate the efficacy, safety, and tolerability of inclisiran in adolescents diagnosed with homozygous familial hypercholesterolaemia (ORION-13) or heterozygous familial hypercholesterolaemia (ORION-16).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study design<\/jats:title>\n                  <jats:p>ORION-13 and ORION-16 are both two-part (1-year double-blind inclisiran vs. placebo\/1 year open-label inclisiran) multicentre trials including adolescents aged 12 to &amp;lt;18 years diagnosed with familial hypercholesterolaemia. ORION-13 will include \u223c12 participants diagnosed with homozygous familial hypercholesterolaemia and ORION-16 will include \u223c150 participants diagnosed with heterozygous familial hypercholesteroleamia. The primary endpoint is the percentage change in LDL-C from baseline to Day 330. Secondary efficacy and safety endpoints include changes in other lipid parameters and treatment-emergent adverse events as well as laboratory parameters and vital signs. Exploratory endpoints include individual responsiveness of the participants and change in LDL-C according to the type of underlying causal mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trial Registration<\/jats:title>\n                  <jats:p>https:\/\/www.clinicaltrials.gov\/. Unique identifier: NCT04659863 (ORION-13) and NCT04652726 (ORION-16).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwac025","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T04:24:42Z","timestamp":1644899082000},"page":"1361-1368","source":"Crossref","is-referenced-by-count":37,"title":["Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia"],"prefix":"10.1093","volume":"29","author":[{"given":"M Doortje","family":"Reijman","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Amsterdam UMC, Location AMC , Meibergdreef 9 , 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Global Drug Development, Cardiovascular, Renal and Metabolism, Novartis Pharma AG , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L H","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Paediatric Cardiology, Department of Paediatrics, University of Wisconsin School of Medicine and Public Health , Madison, WI , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bruckert","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Prevention of Cardiovascular Disease, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Stratz","sequence":"additional","affiliation":[{"name":"Global Drug Development, Cardiovascular, Renal and Metabolism, Novartis Pharma AG , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep C","family":"Defesche","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC, Location AMC, University of Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":false,"given":"Robert A","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University , London, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5671","authenticated-orcid":false,"given":"Albert","family":"Wiegman","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Amsterdam UMC, Location AMC , Meibergdreef 9 , 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"2022122818321916000_zwac025-B1","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1093\/eurheartj\/ehv157","article-title":"Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment","volume":"36","author":"Wiegman","year":"2015","journal-title":"Eur Heart J"},{"key":"2022122818321916000_zwac025-B2","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/eurheartj\/ehu274","article-title":"Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. 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