Efficacy and Safety of Evolocumab in Chinese Patients with Primary Hypercholesterolemia and Mixed Dyslipidemia: 12-Week Primary Results of the HUA TUO 华佗 Randomized Clinical Trial

Introduction Evolocumab, a fully human proprotein convertase/subtilisin kexin type 9 inhibitor antibody, significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes mellitus and hyperlipidemia and mixed dyslipidemia. This 12-week study evaluated the efficacy and safety of evolocumab in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia at different levels of cardiovascular disease risk. Methods HUA TUO was a 12-week randomized, double-blind, placebo-controlled study. Chinese patients aged 18 years or older on stable optimized statin therapy were randomized 2:2:1:1 to receive evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg monthly (QM), or a matching placebo. The coprimary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12 and at week 12. Results Overall, 241 randomized patients (mean [standard deviation] age, 60.2 [10.3] years) received evolocumab 140 mg Q2W ( n = 79), evolocumab 420 mg QM ( n = 80), placebo Q2W ( n = 41), or placebo QM ( n = 41). At weeks 10 and 12, the placebo-adjusted least-squares mean percent change from baseline in LDL-C for the evolocumab 140 mg Q2W group was − 70.7% (95% CI − 78.0% to − 63.5%); − 69.7% (95% CI − 76.5% to − 63.0%) for the evolocumab 420 mg QM group. Significant improvements in all other lipid parameters were observed with evolocumab. The patient incidence of treatment-emergent adverse events was similar between the treatment groups and across dosing regimens. Conclusion In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, 12-week treatment with evolocumab significantly lowered LDL-C and other lipids, and was safe and well tolerated (NCT03433755). Graphical Abstract