Apolipoprotein CIII (APOC3) and angiopoietin-like protein 3 (ANGPTL3) inhibitors: current evidence and future directions
Year: 2025
Type: article
Abstract: Familial chylomicronemia syndrome (FCS) and homozygous familial hypercholesterolemia (HoFH) are rare genetic disorders characterized by profound dyslipidemia and high residual cardiovascular risk, for which conventional therapies have demonstrated limited efficacy. Recent advances in antisense oligonucleotide and small interfering RNA (siRNA)–based therapies targeting apolipoprotein CIII (APOC3) and angiopoietin-like protein 3 (ANGPTL3) have introduced promising treatment options. APOC3 inhibitors such as volanesorsen and olezarsen have been shown to markedly reduce triglyceride (TG) levels and lower the incidence of pancreatitis in individuals with FCS and severe hypertriglyceridemia. siRNA-based plozasiran has produced durable TG-lowering effects with favorable tolerability, although mild hyperglycemia has been observed in individuals with diabetes. In parallel, ANGPTL3 inhibition through monoclonal antibodies (e.g., evinacumab) or RNA inhibitor-based agents (e.g., zodasiran) enables low-density lipoprotein (LDL) receptor–independent LDL cholesterol reduction, offering a valuable therapeutic option for people with HoFH. These agents may help mitigate residual atherosclerotic cardiovascular disease risk in populations insufficiently managed by traditional lipid-lowering therapies. Nevertheless, cardiovascular outcome trials remain unavailable, and long-term benefits have yet to be established. Furthermore, high costs and restricted access pose additional barriers, especially in countries such as Korea, where regulatory approval and importation are pending. To maximize their global impact, cost-effective strategies and equitable access must be prioritized.
Author: Jee Hee Yoo
Institution: Chung-Ang University Gwangmyeong Hospital
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415455334