Development of proprotein convertase subtilisin/kexin type 9 inhibitors and the clinical potential of monoclonal antibodies in the management of lipid disorders

Abstract

Sanjiv Gupta Department of Interventional Cardiology, Santokba Durlabhji Memorial Hospital Cum Medical Research Institute, Jaipur, India Abstract: The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of published long-term ODYSSEY and OSLER studies are summarized. There have been three excellent meta-analysis studies on PCSK9 inhibitors which are outlined. The complex problem of cost-effectiveness was carefully evaluated by the Institute for Clinical and Economic Review (ICER). The draft report (ICER-2015) is summarized herewith. The cardiovascular outcome trials with Evolocumab (FOURIER), Alirocumab (ODYSSEY OUTCOME) and Bococizumab (SPIRE-1 and SPIRE-2) are the ongoing clinical trials, and their results are expected in 2017–2018. The search for new cost-effective analogs of PCSK9 inhibitors is ongoing. Keywords: PCSK9, LDLc, ASCVD

Keywords

• PCSK-9
• LDLc
• ASVCD