Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials

• Published in: European heart journal Vol. 35; no. 33; pp. 2249 - 2259
• Main Authors: Stein, Evan A, Giugliano, Robert P, Koren, Michael J, Raal, Frederick J, Roth, Eli M, Weiss, Robert, Sullivan, David, Wasserman, Scott M, Somaratne, Ransi, Kim, Jae B, Yang, Jingyuan, Liu, Thomas, Albizem, Moetaz, Scott, Rob, Sabatine, Marc S
• Format: Journal Article
• Language: English
• Published: England 01.09.2014
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - adverse effects; Azetidines - administration & dosage; Clinical Trials, Phase II as Topic; Ezetimibe; Female; Humans; Hyperlipidemias - drug therapy; Lipid Metabolism - drug effects; Male; Middle Aged; Proprotein Convertase 9; Proprotein Convertases - immunology; Randomized Controlled Trials as Topic; Serine Endopeptidases - immunology; Treatment Outcome; Low-density lipoprotein cholesterol; Proprotein convertase subtilizin/kexin type 9; Randomized controlled trials
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehu085

Prior trials with monoclonal antibodies to proprotein convertase subtilizin/kexin type 9 (PCSK9) reported robust low density lipoprotein cholesterol (LDL-C) reductions. However, the ability to detect potentially beneficial changes in other lipoproteins such as lipoprotein (a), triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (Apo) A1, and adverse events (AEs) was limited by sample sizes of individual trials. We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9. The trials randomized 1359 patients to various doses of subcutaneous evolocumab every 2 weeks (Q2W) or 4 weeks (Q4W), placebo, or ezetimibe for 12 weeks; 1252 patients contributed to efficacy and 1314, to safety analyses. Mean percentage (95% CI) reductions in LDL-C vs. placebo ranged from 40.2% (44.6%, 35.8%) to 59.3% (63.7%, 54.8%) among the evolocumab groups (all P < 0.001). Statistically significant reductions in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides and lipoprotein (a) [Lp(a)], and increases in HDL-C were also observed. Adverse events (AEs) and serious AEs with evolocumab were reported in 56.8 and 2.0% of patients, compared with 49.2% and 1.2% with placebo. Adjudicated cardiac and cerebrovascular events were reported in 0.3 and 0% in the placebo and 0.9 and 0.3% in the evolocumab arms, respectively. In addition to LDL-C reduction, evolocumab, dosed either Q2W or Q4W, demonstrated significant and favourable changes in other atherogenic and anti-atherogenic lipoproteins, and was well tolerated over the 12-week treatment period.