Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial

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dc.authoridKAYIKCIOGLU, MERAL/0000-0003-3692-5227
dc.authoridRaal, FJ/0000-0002-9170-7938
dc.authoridScott, Russell/0000-0002-2107-6480
dc.authoridStein, Evan/0000-0001-7147-5394
dc.authorscopusid7003901975
dc.authorscopusid57211093318
dc.authorscopusid7404341582
dc.authorscopusid7005939626
dc.authorscopusid57202435704
dc.authorscopusid57202353075
dc.authorscopusid58694080100
dc.authorwosidKAYIKCIOGLU, MERAL/B-1486-2018
dc.authorwosidRaal, FJ/ABD-5111-2021
dc.contributor.authorRaal, Frederick
dc.contributor.authorFourie, Nyda
dc.contributor.authorScott, Russell
dc.contributor.authorBlom, Dirk
dc.contributor.authorDe Vries Basson, Matthys
dc.contributor.authorKayikcioglu, Meral
dc.contributor.authorCaldwell, Kate
dc.date.accessioned2024-08-25T18:36:02Z
dc.date.available2024-08-25T18:36:02Z
dc.date.issued2023
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground and Aims Lerodalcibep, a novel small recombinant fusion protein of a proprotein convertase subtilisin/kexin type 9 gene-binding domain (adnectin) and human serum albumin, demonstrated highly effective low-density lipoprotein cholesterol (LDL-C) reduction with monthly 300 mg in 1.2 mL subcutaneous dosing in Phase 2. In this global Phase 3 trial, the safety and efficacy of lerodalcibep were evaluated in heterozygous familial hypercholesterolaemia patients requiring additional LDL-C lowering.Methods Patients were randomized 2:1 to monthly subcutaneous injections of either lerodalcibep 300 mg or placebo for 24 weeks. The primary efficacy endpoints were the per cent change from baseline in LDL-C at Week 24 and the mean of Weeks 22 and 24.Results In 478 randomized subjects [mean age (range); 53 (18-80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L], lerodalcibep reduced LDL-C, compared with placebo by an absolute amount of 2.08 (0.11) mmol/L [LS mean (SE); 95% confidence interval -2.30 to -1.87] with a percentage difference of -58.61 (3.25)% at Week 24 and by 2.28 (0.10) mmol/L (95% confidence interval -2.47 to -2.09) with a percentage difference of -65.0 (2.87)% at the mean of Weeks 22 and 24 (P < .0001 for all). With lerodalcibep, 68% of subjects achieved both a reduction in LDL-C = 50% and the recommended European Society of Cardiology LDL-C targets during the study. Except for mild injection site reactions, treatment-emergent adverse events were similar between lerodalcibep and placebo.Conclusions Lerodalcibep, a novel anti-proprotein convertase subtilisin/kexin type 9 gene small binding protein dosed monthly as an alternative to monoclonal antibodies, significantly reduced LDL-C in subjects with heterozygous familial hypercholesterolaemia with a safety profile similar to placebo.en_US
dc.description.sponsorshipThe authors offer their appreciation to all the investigators, study site staff, and patient volunteers who participated in the study, especially during the height of the COVID-19 pandemic.en_US
dc.description.sponsorshipThe authors offer their appreciation to all the investigators, study site staff, and patient volunteers who participated in the study, especially during the height of the COVID-19 pandemic.en_US
dc.identifier.doi10.1093/eurheartj/ehad596
dc.identifier.issn0195-668X
dc.identifier.issn1522-9645
dc.identifier.pmid37639462en_US
dc.identifier.scopus2-s2.0-85173750898en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1093/eurheartj/ehad596
dc.identifier.urihttps://hdl.handle.net/11454/100503
dc.identifier.wosWOS:001062794800001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherOxford Univ Pressen_US
dc.relation.ispartofEuropean Heart Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240825_Gen_US
dc.subjectLerodalcibepen_US
dc.subjectLow-density lipoprotein cholesterolen_US
dc.subjectFamilial hypercholesterolaemiaen_US
dc.subjectDouble-Blinden_US
dc.subjectLdl-Cen_US
dc.subjectPcsk9en_US
dc.subjectCholesterolen_US
dc.subjectPrevalenceen_US
dc.subjectAlirocumaben_US
dc.subjectEvolocumaben_US
dc.titleLong-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trialen_US
dc.typeArticleen_US

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