{"id":"51dfa0f13e51","type":"article","url":"https://hartvaat.nl/2019/08/06/angptl3-remming-met-monoklonaal-antilichaam-verlaagt-triglyceriden/","title":"ANGPTL3-remming met monoklonaal antilichaam verlaagt triglyceriden","title_en":"Inhibition of Angiopoietin-Like Protein 3 With a Monoclonal Antibody Reduces Triglycerides in Hypertriglyceridemia.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["ace-remmers"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.118.039107","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.118.039107","authors":["Zahid Ahmad","Poulabi Banerjee","Sara Hamon","Kuo-Chen Chan","Aurelie Bouzelmat","William J Sasiela","Robert Pordy","Scott Mellis","Hayes Dansky","Daniel A Gipe","Richard L Dunbar"],"significance":7,"published":"2019-08-06","source_date":"2019-08-06","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/fibraten-bij-hypertriglyceridemie/"],"congress":"","summary_en":"This study demonstrated that ANGPTL3 inhibition with a monoclonal antibody (evinacumab) effectively lowers triglycerides in patients with severe hypertriglyceridemia, establishing a new mechanism for treating this difficult lipid disorder.","created":"2026-07-03T10:28:04Z","updated":"2026-07-03T13:27:16Z","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 remming van ANGPTL3 met een monoklonaal antilichaam voor triglyceridenverlaging bij ernstige hypertriglyceridemie.","abstract_original":"BACKGROUND: Hypertriglyceridemia is associated with increased cardiovascular risk and may be caused by impaired lipoprotein clearance. Angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity, increasing triglycerides and other lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic individuals. Results from 2 Phase 1 studies in hypertriglyceridemic subjects are reported here. METHODS: Subjects with triglycerides >150 but ≤450 mg/dL and low-density lipoprotein cholesterol ≥100 mg/dL (n=83 for single ascending dose study [SAD]; n=56 for multiple ascending dose study [MAD]) were randomized 3:1 to evinacumab:placebo. SAD subjects received evinacumab subcutaneously at 75/150/250 mg, or intravenously at 5/10/20 mg/kg, monitored up to day 126. MAD subjects received evinacumab subcutaneously at 150/300/450 mg once weekly, 300/450 mg every 2 weeks, or intravenously at 20 mg/kg once every 4 weeks up to day 56 with 6 months of follow-up. The primary outcomes were incidence and severity of treatment-emergent adverse events. Efficacy analyses included changes in triglycerides and other lipids over time. RESULTS: In the SAD, 32 (51.6%) versus 9 (42.9%) subjects on evinacumab versus placebo reported treatment-emergent adverse events. In the MAD, 21 (67.7%) versus 9 (75.0%) subjects on subcutaneously evinacumab versus placebo and 6 (85.7%) versus 1 (50.0%) on intravenously evinacumab versus placebo reported treatment-emergent adverse events. No serious treatment-emergent adverse events or events leading to death or treatment discontinuation were reported. Elevations in alanine aminotransferase (7 [11.3%] SAD), aspartate aminotransferase (4 [6.5%] SAD), and creatinine phosphokinase (2 [3.2%) SAD, 1 [14.3%] MAD) were observed with evinacumab (none in the placebo groups), which were single elevations and were not dose-related. Dose-dependent reductions in triglycerides were observed in both studies, with maximum reduction of 76.9% at day 3 with 10 mg/kg intravenously (P<0.0001) in the SAD and of 83.1% at day 2 with 20 mg/kg intravenously once every 4 weeks (P=0.0003) in the MAD. Significant reductions in other lipids were observed with most evinacumab doses versus placebo. CONCLUSION: Evinacumab was well-tolerated in 2 Phase 1 studies. Lipid changes in hypertriglyceridemic subjects were similar to those observed with ANGPTL3 loss-of-function mutations. Because the latter is associated with reduced cardiovascular risk, ANGPTL3 inhibition may improve clinical outcomes. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifiers: NCT01749878 and NCT02107872."}