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

Eli M Roth; Marja-Riitta Taskinen; Henry N Ginsberg; John J P Kastelein; Helen M Colhoun; Jennifer G Robinson; Laurence Merlet; Robert Pordy; Marie T Baccara-Dinet

doi:10.1016/j.ijcard.2014.06.049

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

Journal article

Open access

Peer reviewed

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

Eli M Roth, Marja-Riitta Taskinen, Henry N Ginsberg, John J P Kastelein, Helen M Colhoun, Jennifer G Robinson, Laurence Merlet, Robert Pordy and Marie T Baccara-Dinet

International journal of cardiology, Vol.176(1), pp.55-61

09/2014

DOI: 10.1016/j.ijcard.2014.06.049

PMID: 25037695

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Abstract

Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy. 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 10mg/day (n=51) or alirocumab 75 mg subcutaneously (via 1-mL 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. Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and 138.3 (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). 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.

Proprotein Convertases - antagonists & inhibitors

Hypercholesterolemia - blood

Double-Blind Method

Humans

Middle Aged

Ezetimibe

Antibodies, Monoclonal - therapeutic use

Male

Hypercholesterolemia - drug therapy

Anticholesteremic Agents - therapeutic use

Azetidines - therapeutic use

Hypercholesterolemia - diagnosis

Female

Aged

Serine Endopeptidases

Proprotein Convertase 9

Details

Title: Subtitle: Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial
Creators: Eli M Roth - The Sterling Research Group, Cincinnati, OH, USA. Electronic address: eroth@sterlingresearch.org
Marja-Riitta Taskinen - Cardiovascular Research Unit, Diabetes and Obesity Research Program, University of Helsinki, Finland
Henry N Ginsberg - Columbia University, New York, NY, USA
John J P Kastelein - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Helen M Colhoun - Medical Research Institute, University of Dundee, Dundee, UK
Jennifer G Robinson - College of Public Health, University of Iowa, IA, USA
Laurence Merlet - Sanofi, Paris, France
Robert Pordy - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA
Marie T Baccara-Dinet - Sanofi, Montpellier, France
Resource Type: Journal article
Publication Details: International journal of cardiology, Vol.176(1), pp.55-61
DOI: 10.1016/j.ijcard.2014.06.049
PMID: 25037695
NLM abbreviation: Int J Cardiol
ISSN: 0167-5273
eISSN: 1874-1754
Publisher: Netherlands
Grant note: DOI: 10.13039/100004339, name: Sanofi; DOI: 10.13039/100009857, name: Regeneron
Language: English
Date published: 09/2014
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9983995056002771

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