Related Experiment Video
Updated: Jun 5, 2025
A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
An up-to-date review of emerging biologic therapies for hypercholesterolemia
1Faculty of Medicine, Macau University of Science & Technology, Macau, China.
Insights
New biologic therapies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C3 (apoC3), and angiopoietin-like 3 (ANGPTL3) show promise for managing hypercholesterolemia and reducing cardiovascular risk beyond statins.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Hypercholesterolemia and lipid disorders are primary drivers of atherosclerotic cardiovascular disease (ASCVD).
- Statins, while effective, often fail to achieve target low-density lipoprotein (LDL) cholesterol levels, leaving residual lipid risk factors.
- Novel therapeutic strategies are needed to address inadequacies in current lipid-lowering treatments.
Purpose of the Study:
- To review emerging biologic therapies for hypercholesterolemia.
- To highlight novel drug targets beyond traditional lipid-lowering agents.
- To assess the potential of new biologics in reducing cardiovascular events.
Main Methods:
- PubMed literature search for biologic therapies in development for hypercholesterolemia.
- Review of drugs targeting PCSK9, apoC3, ANGPTL3, and lipoprotein(a) [Lp(a)].
- Analysis of current data on efficacy and potential applications of these novel agents.
Main Results:
- Inhibition of PCSK9 remains a key focus, with new monoclonal antibodies and adenectin therapies showing promise.
- Antisense oligonucleotide (ASO) and small interfering RNA (siRNA) targeting apoC3 and ANGPTL3 are effective for severe hypertriglyceridemia and homozygous familial hypercholesterolemia.
- ASO and siRNA targeting Lp(a) are under investigation in cardiovascular outcome studies.
Conclusions:
- Biologic therapies targeting PCSK9, apoC3, ANGPTL3, and Lp(a) represent a significant advancement in managing hypercholesterolemia.
- These novel agents offer potential for broader applications in reducing cardiovascular risk, especially for patients with residual risk.
- Further clinical studies are crucial to confirm the long-term efficacy and safety of these promising treatments.
Introduction:
Hypercholesterolemia and other lipid disorders are major causes of atherosclerotic cardiovascular disease (ASCVD). Statins have been the mainstay of lipid-lowering therapy for many years, but they may not be adequate to achieve the target low-density lipoprotein (LDL) cholesterol levels and there are other residual lipid risk factors.
Areas Covered:
This article reviews the biologic therapies in development for hypercholesterolemia identified by a PubMed search. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major focus, but the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3) that were originally developed to reduce the levels of triglyceride-rich lipoproteins are now being explored to reduce cardiovascular events in a wider range of patients. A brief overview of biologic therapies targeting lipoprotein(a) [Lp(a)] is also proved.
Expert Opinion:
Inhibition of PCSK9 remains an attractive target. In addition to the currently available monoclonal antibodies (mAbs) and small interfering RNA (siRNA), new mAbs and the adenectin lerodalcibep are promising therapies. The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies.
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:18Cardiovascular Drugs: Classification based on Therapeutic Indications
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...