Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial

Eli M. Roth (Lead / Corresponding author), Marja-Riitta Taskinen, Henry N. Ginsberg, John J. P. Kastelein, Helen M. Colhoun, Jennifer G. Robinson, Laurence Merlet, Robert Pordy, Marie T. Baccara-Dinet

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    Abstract

    Background:Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy. Methods In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events = 1%–<5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was = 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.Results: Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p < 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p < 0.0001).At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (< 2% and < 4% of alirocumab and ezetimibe patients,
    respectively). Conclusions: Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide = 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.

    Original languageEnglish
    Pages (from-to)55-61
    Number of pages7
    JournalInternational Journal of Cardiology
    Volume176
    Issue number1
    Early online date2 Jul 2014
    DOIs
    Publication statusPublished - Sep 2014

    Keywords

    • PCSK9
    • Monoclonal antibodies
    • Cholesterol-lowering drugs
    • HYPERCHOLESTEROLEMIA
    • LDL-C
    • Alirocumab

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    Roth, E. M., Taskinen, M-R., Ginsberg, H. N., Kastelein, J. J. P., Colhoun, H. M., Robinson, J. G., Merlet, L., Pordy, R., & Baccara-Dinet, M. T. (2014). Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial. International Journal of Cardiology, 176(1), 55-61. https://doi.org/10.1016/j.ijcard.2014.06.049