{"id":"ae2e75ba4f08","type":"article","url":"https://hartvaat.nl/2020/10/21/vupanorsen-angptl3-antisense-en-triglyceriden-ehj/","title":"Vupanorsen ANGPTL3-antisense en triglyceriden: EHJ","title_en":"Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":[],"journal":"European heart journal","doi":"10.1093/eurheartj/ehaa689","source_url":"https://doi.org/10.1093/eurheartj/ehaa689","authors":["Daniel Gaudet","Ewa Karwatowska-Prokopczuk","Seth J Baum","Eunju Hurh","Joyce Kingsbury","Victoria J Bartlett","Amparo L Figueroa","Philip Piscitelli","Walter Singleton","Joseph L Witztum","Richard S Geary","Sotirios Tsimikas","Louis St L O'Dea"],"significance":7,"published":"2020-10-21","source_date":"2020-10-21","image":"","kennis":[],"congress":"","summary_en":"This study of vupanorsen, a GalNAc-conjugated antisense oligonucleotide targeting ANGPTL3, demonstrated significant reductions in triglycerides and atherogenic lipoproteins with improved hepatic targeting, advancing the ANGPTL3 inhibition approach for dyslipidemia.","created":"2026-07-03T10:28:50Z","updated":"2026-07-03T13:27:59Z","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":"EHJ studie van vupanorsen, een GalNAc-geconjugeerd antisense-middel tegen ANGPTL3-mRNA, voor triglyceriden- en atherogene lipoproteïneverlaging.","abstract_original":"AIMS: Loss-of-function mutations in ANGPTL3 are associated with beneficial effects on lipid and glucose metabolism and reduced risk of coronary artery disease. Vupanorsen (AKCEA-ANGPTL3-L Rx ) is an N-acetyl galactosamine-conjugated antisense oligonucleotide targeted to the liver that selectively inhibits angiopoietin-like 3 (ANGPTL3) protein synthesis. METHODS AND RESULTS: This was a double-blind, placebo-controlled, dose-ranging, Phase 2 study. Patients (N =105) with fasting triglycerides >150 mg/dL (>1.7 mmol/L), type 2 diabetes, and hepatic steatosis were treated for 6 months with 40 or 80 mg every 4 weeks (Q4W), or 20 mg every week (QW) of vupanorsen, or placebo given subcutaneously. The primary efficacy endpoint was per cent change in fasting triglycerides from baseline at 6 months. Median baseline triglycerides were 2.84 mmol/L (252 mg/dL). Significant reductions in triglycerides of 36%, 53%, 47%, and in ANGPTL3 of 41%, 59%, 56%, were observed in the 40 mg Q4W, 80 mg Q4W, and 20 mg QW groups, respectively, compared with 16% reduction in triglycerides and 8% increase in ANGPTL3 in placebo. Compared with placebo, vupanorsen 80 mg Q4W reduced apolipoprotein C-III (58%), remnant cholesterol (38%), total cholesterol (19%), non-high-density lipoprotein cholesterol (HDL-C; 18%), HDL-C (24%), and apolipoprotein B (9%). There was no improvement in glycaemic parameters, or hepatic fat fraction. Treatment with vupanorsen was not associated with clinically significant changes in platelet counts, and the most common adverse events were those at the injection site, which were generally mild. CONCLUSION: Vupanorsen results in a favourable lipid/lipoprotein profile and provides a potential strategy for residual cardiovascular risk reduction."}