{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:27:04Z","timestamp":1789820824136,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"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":[[2025,6,24]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Homozygous familial hypercholesterolemia (HoFH) is a genetic disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C) present from birth, leading to early-onset and progressive atherosclerotic cardiovascular disease. Early treatment initiation is crucial for cardiovascular risk reduction; however, many patients do not reach LDL-C treatment goals. Inclisiran, a small interfering RNA targeting hepatic PCSK9 (proprotein convertase subtilisin\/kexin type 9), is effective and well tolerated in adult patients with hyperlipidemia; however, it has not yet been studied in pediatric patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Herein we report results of the 1-year, double-blind, placebo-controlled part of the phase 3 study ORION-13 (Study to Evaluate Efficacy and Safety of Inclisiran in Adolescents With Homozygous Familial Hypercholesterolemia) in adolescents with HoFH. This 2-part multicenter study included 13 patients \u226512 to &lt;18 years of age with a genetic diagnosis of HoFH (excluding LDL [low-density lipoprotein] receptor [\n                      <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n                      ] null\/null genotypes) and elevated LDL-C levels (&gt;130 mg\/dL) on maximally tolerated statin treatment, with or without other lipid-lowering therapies. Eligible patients were randomized 2:1 to receive either 300 mg of inclisiran sodium or placebo, administered on days 1, 90, and 270. The primary end point was the mean percentage change in LDL-C from baseline to day 330.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>The mean age of patients was 14.8 years, and mean baseline LDL-C was 272 mg\/dL. The placebo-adjusted mean (95% CI) percentage change in LDL-C from baseline to day 330 was \u221233.3% (\u221259.2% to \u22127.3%). Six of 9 (66.7%) inclisiran-treated patients (versus 1 of 4 [25%] on placebo) achieved a &gt;15% reduction in LDL-C, and 5 of 9 (55.6%) inclisiran-treated patients (versus none on placebo) achieved a &gt;20% reduction. The placebo-adjusted mean (95% CI) percentage change in PCSK9 from baseline to day 330 was \u221260.2% (\u221279.8% to \u221240.7%); corresponding changes in apolipoprotein B, non\u2013high-density lipoprotein cholesterol, and total cholesterol were \u221223.0%, \u221232.7%, and \u221227.8%, respectively. No serious adverse events, treatment discontinuations because of adverse events, or deaths occurred. No new safety findings were reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In a 1-year randomized controlled study (part 1 of ORION-13), inclisiran was effective in lowering LDL-C in adolescents with HoFH and was well tolerated. These results support inclisiran as a potentially useful addition for the treatment of adolescents with HoFH and a minimum of LDLR residual activity.<\/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: NCT04659863.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.124.073233","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:07:22Z","timestamp":1747717642000},"page":"1758-1766","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Efficacy and Safety of Inclisiran in Adolescents With Genetically Confirmed Homozygous Familial Hypercholesterolemia: Results From the Double-Blind, Placebo-Controlled Part of the ORION-13 Randomized Trial"],"prefix":"10.1161","volume":"151","clinical-trial-number":[{"clinical-trial-number":"nct04659863","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 (A.W.), Amsterdam University Medical Center, Location Academic Medical Center, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5238-3002","authenticated-orcid":true,"given":"Amy L.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison (A.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":true,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (R.A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-9629","authenticated-orcid":true,"given":"Eric","family":"Bruckert","sequence":"additional","affiliation":[{"name":"Centre de Sant\u00e9 Ellasante, Paris, France (E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-3442","authenticated-orcid":true,"given":"Anja","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland (A.S., A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Lesogor","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland (A.S., A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Novartis Pharma Co, Ltd, China (Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep","family":"Defesche","sequence":"additional","affiliation":[{"name":"Department of Human Genetics (J.D.), Amsterdam University Medical Center, Location Academic Medical Center, University of Amsterdam, The 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