Lipid-lowering biotechnological drugs: From monoclonal antibodies to antisense therapies-a clinical perspective

Authors

Xiaoming Jia, Baylor College of Medicine, United States
Jing Liu, Baylor College of Medicine, United States
Anurag Mehta, Emory University School of Medicine, United States
Christie M. Ballantyne, Baylor College of Medicine, United States
Salim S. Virani, Baylor College of Medicine, United StatesFollow

Document Type

Article

Department

Office of the Provost; Cardiology

Abstract

Purpose: While low density lipoprotein cholesterol (LDL-C) remains a key contributor of atherosclerotic cardiovascular disease (ASCVD), additional risk factors identified through epidemiological and genetic studies have ushered in a fertile era of drug discovery in lipid-lowering therapy. Unlike contemporary small molecule medications, many of the novel agents are biologics utilizing monoclonal antibody (mAb) or RNA interference (RNAi) technologies. This report aims to review the evidence to date, focusing on completed and ongoing clinical trials and how these new agents will impact clinical practice.
Methods: We review data from pertinent studies on lipid-lowering biologics in clinical use or have translated to human studies and are undergoing clinical trials.
Results: Several targets affecting lipid metabolism have been identified to be causally associated with ASCVD including proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C3 (APOC3), and lipoprotein (a) (Lp[a]). Biotechnological modalities that have been developed for these targets include mAb, small interfering RNA (siRNA), and anti-sense oligonucleotide (ASO) agents. Agents such as alirocumab and evolocumab have shown efficacy in risk reduction of ASCVD in cardiovascular outcome trials and have been incorporated into evidence-based practice guidelines. Other agents included in this review are in various stages of clinical trials and have shown significant efficacy in the reduction of lipid parameters.
Conclusion: The development of new biologics targeting lipid risk factors will provide clinicians additional tools to reduce the risk for ASCVD. Important factors to consider will be cost-effectiveness and improving methods to personalize treatments to risk factors.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Cardiovascular drugs and therapy

Recommended Citation

Jia, X., Liu, J., Mehta, A., Ballantyne, C. M., Virani, S. S. (2020). Lipid-lowering biotechnological drugs: From monoclonal antibodies to antisense therapies-a clinical perspective. Cardiovascular drugs and therapy, 35(6), 1269-1279.
Available at: https://ecommons.aku.edu/provost_office/343