Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk

BACKGROUND: YUKAWA is a 12-week, randomized, double-blind, placebo-controlled, phase 2 study evaluating the efficacy and safety of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. METHODS AND RESULTS: 310 eligible patients receiving stable statin (±ezetimibe) therapy were randomized to 1 of 6 treatments: placebo every 2 weeks (Q2W) or monthly (QM), evolocumab 70 mg or 140 mg Q2W, or evolocumab 280 mg or 420 mg QM. The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) measured by preparative ultracentrifugation (UC). Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C <1.8 mmol/L. Mean (SD) age was 62 (10) years; 37% were female; and the mean (SD) baseline LDL-C was 3.7 (0.5) mmol/L (by UC). Mean (SE) changes vs. placebo in LDL-C were greatest in the high-dose groups: -68.6 (3.0) % and -63.9 (3.2) % with 140 mg Q2W and 420 mg QM dosing, respectively. Up to 96% of evolocumab-treated patients achieved LDL-C <1.8 mmol/L. Adverse events (AEs) were more frequent in evolocumab (51%) vs. placebo (38%) patients; 4 patients taking evolocumab discontinued treatment because of an AE. There were no significant differences in AE rates based on dose or dose frequency. CONCLUSIONS: In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy, evolocumab significantly reduced LDL-C and was well tolerated during this 12-week study.