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

• Published in: International journal of cardiology Vol. 176; no. 1; pp. 55 - 61
• Main Authors: Roth, Eli M, Taskinen, Marja-Riitta, Ginsberg, Henry N, Kastelein, John J.P, Colhoun, Helen M, Robinson, Jennifer G, Merlet, Laurence, Pordy, Robert, Baccara-Dinet, Marie T
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier 01.09.2014
• Subjects: Aged; Antibodies, Monoclonal - therapeutic use; Anticholesteremic Agents - therapeutic use; Azetidines - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Disorders of blood lipids. Hyperlipoproteinemia; Double-Blind Method; Ezetimibe; Female; Heart; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - diagnosis; Hypercholesterolemia - drug therapy; Immunomodulators; Male; Medical sciences; Metabolic diseases; Middle Aged; Pharmacology. Drug treatments; Proprotein Convertase 9; Proprotein Convertases - antagonists & inhibitors; Serine Endopeptidases; Apo; apolipoprotein; NCEP-ATPIII; LS; ITT; PCSK9; lower limit of normal; treatment-emergent adverse events; Lp(a); not elsewhere classified; HDL-C; randomization; ULN; high-density lipoprotein cholesterol; serious adverse events; systematic coronary risk estimation; AE; body mass index; adverse event; IQR; Non-HDL-C; standard error; CVD; EZE; subcutaneously; Hypercholesterolemia; ezetimibe; least squares; Monoclonal antibodies; SAEs; modified intent-to-treat; Alirocumab; standard deviation; every 2 weeks; SCORE; glycated hemoglobin A1c; LDL-C; low-density lipoprotein cholesterol; interquartile range; intent-to-treat; mITT; LLN; lipoprotein (a); SC; SD; low-density lipoprotein receptors; R; SE; proprotein convertase subtilisin/kexin 9; HbA1c; LDLR; National Cholesterol Education Program Adult Treatment Panel III; BMI; non-high-density lipoprotein cholesterol; cardiovascular disease; TGs; EOT; triglycerides; cardiovascular; NEC; Cholesterol-lowering drugs; end of treatment; upper limit of normal; CV; Q2W; TEAEs; Phase III trial; Ezetimibe; Lipids; Cardiovascular disease; Hyperlipoproteinemia; Monoclonal antibody; Result; Lipoprotein LDL; Randomization; Immunotherapy; Dyslipemia; Cardiology; Human; Metabolic diseases; Cholesterol LDL; Patient; Immunomodulator; Treatment; Double blind study; Inhibitor; Comparative study; Antilipemic agent
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2014.06.049

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) 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). 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.