Abstract 10451: Efficacy and Safety of Ebronucimab, a Monoclonal Antibody Against Pcsk9, in Patients With Hyperlipidemia: Result From a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Introduction Elevated low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to Low-density lipoprotein receptors (LDL-R) and triggers their degradation. Inhibiting PCSK9 activity results in lowering LDL-C levels and further reduceing the risk of cardiovascular events. Ebronucimab (AK102) is a novel fully human immunoglobulin G1 (IgG1) monoclonal antibody against PCSK9. Objectives To evaluate the safety, efficacy of ebronucimab and further identify the optimal dosing scheme in patients with hyperlipidemia. Methods A total of 260 Chinese patients with hyperlipidemia (≧18 years, male or female) were planned to be enrolled, and randomized to receive ebronucimab 450 mg every 4 weeks (q4w), 300 mg q4w, 150 mg q2w, 75 mg q2w or matching placebo via subcutaneous injection. The patients were treated up to 12 weeks (day 85). Serum samples were collected at preselected timepoints to analyze the lipid profiles. Results Efficacy Ebronucimab showed significant and dose-dependent LDL-C reductions from baseline. At week 12, the mean reductions in LDL-C were 65.48 %, 48.14%, 63.69% and 37.39% for 450 mg q4w, 300 mg q4w, 150 mg q2w and 75 mg q2w dose groups, respectively. Patients in the 450 mg q4w and 150 mg q2w groups achieved higher and more sustained LDL-C reduction compared with other dose groups. Similar trend was observed in serum levels of total cholesterol (TC), apolipoprotein B (ApoB), lipoprotien (a) (LP[a]). Safety A total of 49.6% (130/262) patients experienced at least 1 treatment-emergent adverse event (TEAE), 109 patients (109/210 [51.9%]) in ebronucimab groups and 21 patients (21/52 [40.4%]) in the placebo group. Most TEAEs were mild and moderate. No adverse events were apparently dose dependent with ebronucimab. The overall incidence of serious adverse events (SAEs) was 3.4 % (9/262). Conclusions Ebronucimab was generally safe and well tolerated in Chinese patients with hyperlipidemia. Patients treated with ebronucimab achieved a significant reduction in serum levels of LDL-C and other lipids, especially in 450 mg q4w and 150 mg q2w treatment groups.