Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia

Abstract

Background: A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia.

Methods and results: A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups.

Conclusions: Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

Keywords: PCSK9; hypercholesterolemia; lipid‐lowering therapy; low‐density lipoprotein cholesterol; mixed dyslipidemia.

Figure 1. Patient enrollment and disposition.

A total of 1267 patients were screened, and 806 patients were randomized (1 patient with failed screening was randomized by mistake). If the patient completes the last dosing of the investigational product, the patient is considered to have completed treatment. FAS indicates full analysis set; Q2W, every 2 weeks; Q4W, every 4 weeks; and SS, safety analysis set.

Figure 2. Percentage change in LDL‐C level from baseline to scheduled visits for ongericimab 150 mg every 2 weeks dosing (A) and 300 mg every 4 weeks dosing groups (B).

The percentage changes in LDL‐C level from baseline to scheduled visits were analyzed in the full analysis set using a mixed‐effects model for repeated measures. LDL‐C indicates low‐density lipoprotein cholesterol; and LS, least squares.