An evaluation of the pharmacokinetics of inclisiran in the treatment of atherosclerotic cardiovascular disease. (2nd December 2021)

• Record Type: Journal Article
• Authors: Tomlinson, Brian; Chow, Elaine; Chan, Paul; Lam, Christopher Wai Kei
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 17:Number 12(2021)
• Page Start: 1353
• Page End: 1361
• Publication Date: 2021-12-02
• Subjects: Inclisiran -- low-density lipoprotein cholesterol -- proprotein convertase subtilisin/kexin type 9 -- small interfering RNA -- triantennary N-acetylgalactosamine; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2021.2029402
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction: Inclisiran is a small interfering RNA that inhibits hepatic production of proprotein convertase subtilisin/kexin type 9 (PCSK9) which results in reduction of circulating low-density lipoprotein cholesterol (LDL-C). It can be used alone or in combination with statins or other lipid-lowering therapy. Areas covered: In this article, we review the pharmacokinetics, pharmacodynamics and clinical efficacy of inclisiran based on the published literature. Expert opinion: Inclisiran is a chemically stabilized duplex RNA conjugated with triantennary N-acetylgalactosamine which facilitates rapid and selective liver uptake and the drug is almost entirely removed from the circulation within 24 hours after subcutaneous injection. The duration of action is impressively prolonged and after doses of 300 mg on days one and 90, the dose can be repeated every six months to maintain a durable reduction of LDL-C by about 50%. The efficacy and safety are similar to the monoclonal antibodies targeting PCSK9, evolocumab and alirocumab, and injection site reactions are infrequent and generally mild. The cardiovascular outcome study with inclisiran is ongoing and other long term safety data are keenly awaited. The infrequent dosing regimen offers a major advantage to improve long term compliance and inclisiran may be extensively adopted depending on the cost.