Reduction of Low-Density Lipoprotein Cholesterol by Monoclonal Antibody Inhibition of PCSK9

Author:

Stein Evan A.1,Raal Frederick2

Affiliation:

1. Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio 45215;

2. Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;

Abstract

Published phase I and II trials with two fully human monoclonal antibodies to PCSK9 have provided comprehensive evidence that inhibiting PCSK9 is a very effective method to reduce low-density lipoprotein cholesterol (LDL-C). In all populations studied so far, whether on statins or LDL-C-reducing diet alone, with or without a genetic defect in the LDL receptor, and in subjects intolerant to statins, the LDL-C reductions have been large and consistent. Even the most efficacious statin, rosuvastatin, at its highest dose has not achieved such reductions. The clinical trials have established that monoclonal antibody therapy targeted to PCSK9 may be administered subcutaneously every two or four weeks. Current data suggest these drugs will provide an effective therapeutic option for LDL-C reduction and that, if proven safe in phase III trials, they will be as important to LDL-C control, and likely to cardiovascular disease risk reduction, as statins have been over the past three decades.

Publisher

Annual Reviews

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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