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.

ABSTRACT

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.