{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T08:41:53Z","timestamp":1773477713186,"version":"3.50.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Despite progress in treating homozygous familial hypercholesterolemia, most patients do not achieve low-density lipoprotein cholesterol (LDL-C) targets. This study examined efficacy and safety of the PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitor, alirocumab, in pediatric patients (aged 8\u201317 years) with inadequately controlled homozygous familial hypercholesterolemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>In this open-label, single-arm, multinational, Phase 3 study, patients (n=18) received alirocumab 75 mg or 150 mg (bodyweight &lt;50 kg\/\u226550 kg) every 2 weeks as an adjunct to background treatment. The primary endpoint was percent change in LDL-C from baseline to Week 12. Secondary endpoints included changes in LDL-C and other lipid parameters up to 48 weeks, safety\/tolerability, and alirocumab pharmacokinetics.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              The mean age of patients was 12.4 years; 16\/18 (89%) had mutations in the low-density lipoprotein receptor gene\n              <jats:italic>(LDLR<\/jats:italic>\n              ) and 2\/18 (11%) had mutations in the LDLR adapter protein 1 gene (\n              <jats:italic>LDLRAP1).<\/jats:italic>\n              At baseline, mean LDL-C (standard deviation) was 373.0 (193.5) mg\/dL, which decreased by 4.1% at Week 12 (primary endpoint) and 11.4%, 13.2%, and 0.4% at Weeks 4, 24, and 48, respectively. At Week 12, 9\/18 (50%) patients achieved LDL-C reductions \u226515%. Mean absolute LDL-C decreases ranged from 25 to 52 mg\/dL over follow-up. A post hoc analysis demonstrated heterogeneity of responses according to genotype. There were no unexpected safety\/tolerability findings. Free PCSK9 was reduced to near zero for all patients at Weeks 12 and 24.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The study supports the efficacy and safety of alirocumab as a potential adjunct to treatment for some pediatric patients with homozygous familial hypercholesterolemia.<\/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              ; NCT03510715.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317793","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T09:00:43Z","timestamp":1667466043000},"page":"1447-1457","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia: Phase 3, Multinational Open-Label Study"],"prefix":"10.1161","volume":"42","clinical-trial-number":[{"clinical-trial-number":"nct03510715","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-9629","authenticated-orcid":true,"given":"Eric","family":"Bruckert","sequence":"first","affiliation":[{"name":"H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re, Sorbonne University Paris, France (E.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Caprio","sequence":"additional","affiliation":[{"name":"Yale Pediatric Endocrinology, New Haven, CT (S.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Wiegman","sequence":"additional","affiliation":[{"name":"Department of Metabolic Disorders, Amsterdam UMC, Location AMC, Emma Children\u2019s Hospital, the Netherlands (A.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C. (M.-J.C.)."},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C. (M.-J.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9zar A.","family":"Z\u00e1rate-Morales","sequence":"additional","affiliation":[{"name":"Hospital \u201cPresidente Ju\u00e1rez\u201d del Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), Oaxaca, Oax, M\u00e9xico (C.A.Z.-M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie T.","family":"Baccara-Dinet","sequence":"additional","affiliation":[{"name":"Sanofi, Montpellier, France (M.T.B.-D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garen","family":"Manvelian","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (G.M.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Ourliac","sequence":"additional","affiliation":[{"name":"Aixial, Boulogne-Billancourt, France (A.O.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Scemama","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France (M.S.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen R.","family":"Daniels","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Aurora (S.R.D.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu274"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2017.03.008"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-016-0579-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310217"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv157"},{"key":"e_1_3_3_8_2","unstructured":"European Medicines Agency. 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