{"id":"2f0bb62e9d65","type":"article","url":"https://hartvaat.nl/2025/05/20/angptl3-antilichaam-bij-suboptimaal-gecontroleerde-hyperlipidemie-fase-2/","title":"ANGPTL3-antilichaam bij suboptimaal gecontroleerde hyperlipidemie: fase 2","title_en":"Angiopoietin-Like 3 Antibody Therapy in Patients With Suboptimally Controlled Hyperlipidemia: A Phase 2 Study.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["ace-remmers","ezetimibe","familiaire-hypercholesterolemie","lipidenverlaging"],"journal":"Journal of the American College of Cardiology","doi":"10.1016/j.jacc.2025.03.008","source_url":"https://doi.org/10.1016/j.jacc.2025.03.008","authors":["Xiaojie Xie","Xiaoxia Shi","Yuming Zhang","Shuhong Su","Chenyan Jiang","Liu Miao","Junkui Wang","Daoquan Peng","Lingchun Lv","Xiaohong Chai","Suxin Luo","Yang Zheng","Shan Huang","Dan Zhu","Shangshang Liao","Meng Ren","Xiaohong Gao","Haibo Yang","Hao Zhou","Yuquan He","Yajun Han","Jiahong Xu","Lin Zhang","Laijing Du","Zhuhua Yao","Jianlong Sheng","Xiaoping Peng","Xiaowen Chen","Juxiang Li","Jie Mi","Qiang Lu","Hongju Wang","Zheng Shen","Zhilin Zhao","Feng Gao","Chao Lv","Min Zhu","Ying Zhu","Jian'an Wang"],"significance":7,"published":"2025-05-20","source_date":"2025-05-20","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/","https://hartvaat.nl/kennis/lipiden/ezetimib/"],"congress":"","summary_en":"This phase 2 trial of an ANGPTL3 antibody showed significant LDL and triglyceride lowering in patients with suboptimally controlled hyperlipidemia, expanding the ANGPTL3 inhibition approach to a broader dyslipidemia population.","created":"2026-07-03T10:31:38Z","updated":"2026-07-03T13:30:38Z","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":"Fase 2 trial van een ANGPTL3-antilichaam toonde significante verlaging van LDL en triglyceriden bij suboptimaal gecontroleerde hyperlipidemie. Het middel biedt een nieuw mechanisme voor patiënten die onvoldoende reageren op statines.","abstract_original":"BACKGROUND: Angiopoietin-like 3 (ANGPTL-3) inhibits the activity of lipoprotein lipase and endothelial lipase, increasing both serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. SHR-1918 is a fully human monoclonal antibody against ANGPTL-3. OBJECTIVES: The aim of this study was to assess the lipid-altering efficacy and safety of SHR-1918 in patients at moderate or higher risk of atherosclerotic cardiovascular disease (ASCVD) with suboptimally controlled hyperlipidemia. METHODS: A multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2 study was designed to evaluate the effects of SHR-1918 in hypercholesterolemic patients, who did not achieve optimal LDL-C after 4 to 8 weeks of standard lipid-lowering therapies. A total of 333 patients were enrolled sequentially into 1 of 8 dose cohorts at a 4:1 (active/placebo) ratio. Patients received subcutaneous SHR-1918 at doses of 150, 300, or 600 mg every 4 weeks (Q4W), or SHR-1918 at a dose of 600 mg every 8 weeks (Q8W), alternating with placebo for a total treatment period of 16 weeks. The extension treatment included subcutaneous SHR-1918 at a dose of 150, 300, or 600 mg Q4W over 36 weeks, or SHR-1918 a dose of 600 mg Q8W over 40 weeks and then followed for safety. Prespecified endpoints included percentage change from baseline in LDL-C and TG. Safety was assessed with laboratory test results and by the incidence and severity of adverse events. RESULTS: SHR-1918 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q4W and Q8W administration: 21.7%, 27.3%, and 29.9% with 150, 300, and 600 mg Q4W compared with placebo, respectively, and 22.5% with 600 mg Q8W compared with placebo. SHR-1918 also substantially reduced TG, non-high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein A1, with a better achievement of LDL-C targets. SHR-1918 was generally well-tolerated. CONCLUSIONS: Based on standard lipid-lowering therapy, ANGPTL-3 inhibition with SHR-1918 further reduces LDL-C by 21.7% to 29.9% in patients at moderate or higher risk of ASCVD. These additional reductions are both dose and dosing frequency dependent. (Evaluate the Efficacy and Safety of SHR-1918 in Patients With Hyperlipidemic; NCT06109831)."}