{"id":"532343779f2e","type":"article","url":"https://hartvaat.nl/2019/09/01/galnac-geconjugeerd-antisense-tegen-apoc3-triglyceriden-en-atherogene-lipoprotei/","title":"GalNAc-geconjugeerd antisense tegen APOC3: triglyceriden en atherogene lipoproteïnen","title_en":"N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["pelacarsen","yellow-iii"],"journal":"European heart journal","doi":"10.1093/eurheartj/ehz209","source_url":"https://doi.org/10.1093/eurheartj/ehz209","authors":["Veronica J Alexander","Shuting Xia","Eunju Hurh","Steven G Hughes","Louis O'Dea","Richard S Geary","Joseph L Witztum","Sotirios Tsimikas"],"significance":7,"published":"2019-09-01","source_date":"2019-09-01","image":"","kennis":[],"congress":"","summary_en":"This study of a GalNAc-conjugated antisense oligonucleotide targeting APOC3 mRNA demonstrated potent triglyceride reduction with improved hepatic targeting and lower dosing requirements, advancing the next generation of apoC-III-lowering therapies.","created":"2026-07-03T10:28:08Z","updated":"2026-07-03T13:27:19Z","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":"Studie naar een GalNAc-geconjugeerde antisense-oligonucleotide tegen APOC3-mRNA voor verlaging van triglyceriden en atherogene lipoproteïnen. Volgende generatie lipidentherapie.","abstract_original":"AIMS: Elevated apolipoprotein C-III (apoC-III) levels are associated with hypertriglyceridaemia and coronary heart disease. AKCEA-APOCIII-LRx is an N-acetyl galactosamine-conjugated antisense oligonucleotide targeted to the liver that selectively inhibits apoC-III protein synthesis. METHODS AND RESULTS: The safety, tolerability, and efficacy of AKCEA-APOCIII-LRx was assessed in a double-blind, placebo-controlled, dose-escalation Phase 1/2a study in healthy volunteers (ages 18-65) with triglyceride levels ≥90 or ≥200 mg/dL. Single-dose cohorts were treated with 10, 30, 60, 90, and 120 mg subcutaneously (sc) and multiple-dose cohorts were treated with 15 and 30 mg weekly sc for 6 weeks or 60 mg every 4 weeks sc for 3 months. In the single-dose cohorts treated with 10, 30, 60, 90, or 120 mg of AKCEA-APOCIII-LRx, median reductions of 0, -42%, -73%, -81%, and -92% in apoC-III, and -12%, -7%, -42%, -73%, and -77% in triglycerides were observed 14 days after dosing. In multiple-dose cohorts of 15 and 30 mg weekly and 60 mg every 4 weeks, median reductions of -66%, -84%, and -89% in apoC-III, and -59%, -73%, and -66% in triglycerides were observed 1 week after the last dose. Significant reductions in total cholesterol, apolipoprotein B, non-high-density lipoprotein cholesterol (HDL-C), very low-density lipoprotein cholesterol, and increases in HDL-C were also observed. AKCEA-APOCIII-LRx was well tolerated with one injection site reaction of mild erythema, and no flu-like reactions, platelet count reductions, liver, or renal safety signals. CONCLUSION: Treatment of hypertriglyceridaemic subjects with AKCEA-APOCIII-LRx results in a broad improvement in the atherogenic lipid profile with a favourable safety and tolerability profile. ClinicalTrials.gov Identifier: NCT02900027."}