Alirocumab: PCSK9 inhibitor for LDL cholesterol reduction

Hagai Tavori, Michelle Melone, Shirya Rashid

    Research output: Contribution to journalReview article

    12 Scopus citations

    Abstract

    The proof of concept that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition affects cholesterol levels was first established after the demonstration that PCSK9 loss-of-function mutations result in a significant drop in circulating LDL cholesterol levels. Subsequent studies revealed that PCSK9 binds the epidermal growth factor precursor homology domain-A on the surface LDL Receptor (LDLR) and directs LDLR and PCSK9 for lysosomal degradation. Alirocumab (also known as SAR236553/REGN727) is a monoclonal antibody that binds circulating PCSK9 and blocks its interactions with surface LDLR. Alirocumab clinical trials with different doses on different administration schedules were shown to significantly reduce LDL cholesterol both as a mono-therapy and in combination with statins or ezetimibe. Although there is great potential for anti-PCSK9 therapies in the management of cholesterol metabolism, there is no clear evidence yet that blocking PCSK9 reduces cardiovascular disease outcome. This is being investigated in ongoing Phase III clinical trials with alirocumab.

    Original languageEnglish (US)
    Pages (from-to)1137-1144
    Number of pages8
    JournalExpert Review of Cardiovascular Therapy
    Volume12
    Issue number10
    DOIs
    StatePublished - Oct 1 2014

    Keywords

    • Familial hypercholesterolemia
    • Low-density lipoprotein
    • Low-density lipoprotein receptor
    • Monoclonal antibodies
    • PCSK9

    ASJC Scopus subject areas

    • Internal Medicine
    • Cardiology and Cardiovascular Medicine

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