Efficacy and safety of Ebronucimab, in patients with primary hypercholesterolemia and mixed hyperlipidemia: Results from a randomized, double-blind, placebo-controlled phase III clinical study

Background and Aims: Inhibiting PCSK9 activity results in lowering LDL-C levels and further reducing the risk of cardiovascular events. Ebronucimab (AK102) is a novel fully human immunoglobulin G1 monoclonal antibody against PCSK9. This study aimed to evaluate the safety and efficacy of Ebronucimab in subjects with primary hypercholesterolemia and mixed hyperlipidemia. Methods: A total of 450 patients (male and female) with age ranging from 18 to 80 years were planned to enrolled. There were 4 cohorts (Q2W: 150mg, placebo; Q4W: 450mg, placebo) in this study. In each cohort, subjects were enrolled and randomized in a 2:1:2:1 ratio to receive either Ebdarokimab or matching placebo. Results: Both cohorts (450mg Q4W, 150mg Q2W) can effectively reduce fasting serum LDL-C and keep it stable up to week 12. The percentage change of fasting LDL-C relative to the baseline was 64.90% in 450 mg Q4W group, 59.13% lower than the placebo group. 66.21% in 150 mg Q2W group, and 60.43% lower than the placebo group after treatment. 461 subjects enrolled in safety set. 200(43.4%) subjects experienced at least one treatment-emergent adverse event (TEAE), 143 subjects receiving Ebronucimab and 57 subjects receiving placebo. 64(13.9%) subjects had TEAE (TRAE) related to study drug, including 54(17.5%) jubjects in Ebronucimab group and 10(6.6%) subjects in the placebo group. 14(3.0%) subjects experienced serious adverse event (SAE). Investigators assessed the SAEs were non-related to study drug. No death was reported. Conclusions: Ebronucimab was generally safe and able to lowering serum levels of LDL-C in subjects with primary hypercholesterolemia and mixed hyperlipidemia.