OBJECTIVES: The aim of this study was to compare biweekly and monthly evolocumab 
with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase 
III trial.
BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein 
convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase 
II trials.
METHODS: Patients 18 to 80 years of age with fasting low-density lipoprotein 
cholesterol (LDL-C) ≥100 and <190 mg/dl and Framingham risk scores ≤10% were 
randomized (1:1:1:1:2:2) to oral placebo and subcutaneous (SC) placebo biweekly; 
oral placebo and SC placebo monthly; ezetimibe and SC placebo biweekly; 
ezetimibe and SC placebo monthly; oral placebo and evolocumab 140 mg biweekly; 
or oral placebo and evolocumab 420 mg monthly.
RESULTS: A total of 614 patients were randomized and administered doses. 
Evolocumab treatment reduced LDL-C from baseline, on average, by 55% to 57% more 
than placebo and 38% to 40% more than ezetimibe (p < 0.001 for all comparisons). 
Evolocumab treatment also favorably altered other lipoprotein levels. 
Treatment-emergent adverse events (AEs), muscle-related AEs, and laboratory 
abnormalities were comparable across treatment groups.
CONCLUSIONS: In the largest monotherapy trial using a PCSK9 inhibitor to date, 
evolocumab yielded significant LDL-C reductions compared with placebo or 
ezetimibe and was well tolerated in patients with hypercholesterolemia. 
(Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects 
Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; 
NCT01763827).