{"id":"965aea903547","type":"article","url":"https://hartvaat.nl/2023/10/21/lerodalcibep-bij-familiaire-hypercholesterolemie-liberate-hefh-langetermijndata/","title":"Lerodalcibep bij familiaire hypercholesterolemie: LIBerate-HeFH langetermijndata","title_en":"Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["cetp-remmers","dyslipidemie","ezetimibe","familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening","ldl-cholesterol","lipidenverlaging","lipoproteïne-a","pcsk9-remmers","pelacarsen","vrouwen"],"journal":"European heart journal","doi":"10.1093/eurheartj/ehad596","source_url":"https://doi.org/10.1093/eurheartj/ehad596","authors":["Frederick Raal","Nyda Fourie","Russell Scott","Dirk Blom","Matthys De Vries Basson","Meral Kayikcioglu","Kate Caldwell","David Kallend","Evan Stein"],"significance":7,"published":"2023-10-21","source_date":"2023-10-21","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/familiaire-hypercholesterolemie/","https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/"],"congress":"","summary_en":"Long-term data on lerodalcibep, a novel small recombinant fusion protein PCSK9 inhibitor, showed sustained LDL cholesterol reduction in heterozygous FH patients. The monthly subcutaneous injection offers a new dosing interval between biweekly antibodies and biannual siRNA.","created":"2026-07-03T10:30:38Z","updated":"2026-07-03T13:29:42Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Langetermijndata van lerodalcibep, een klein recombinant fusie-eiwit PCSK9-remmer, toonden duurzame LDL-verlaging bij heterozygote FH. Het middel biedt een maandelijkse subcutane injectie als alternatief voor bestaande PCSK9-remmers.","abstract_original":"BACKGROUND 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."}