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.