Efficacy and safety of ongericimab in Chinese patients with heterozygous familial hypercholesterolemia: A randomized, double-blind, placebo-controlled phase 3 trial

Abstract

Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is a prevalent autosomal dominant disorder of lipid metabolism but severely underdiagnosed and undertreated in China. This phase 3 trial aims to evaluate the efficacy and safety of ongericimab, a novel monoclonal antibody that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), in Chinese patients with HeFH.

Methods: Patients who have been diagnosed with definite HeFH according to Dutch Lipid Clinical Network criteria and receiving stable and optimized lipid-lowering therapy were enrolled. A total of 135 patients were randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks (Q2W), or ongericimab 450 mg or matching placebo every 4 weeks (Q4W) for 24 weeks. Patients were stratified according to the use of high-intensity statins. The primary endpoint was the percentage change in LDL-C from baseline to week 24.

Results: Our findings demonstrated that treatment with ongericimab resulted in a significant reduction in LDL-C at week 24. The least-squares mean difference was -69.4 % (95 % confidence interval [CI]: -80.9 %, -57.9 %; p < 0.0001) for the ongericimab 150 mg Q2W group, and -80.6 % (95 % CI: -92.1 %, -69.1 %; p < 0.0001) for ongericimab 450 mg Q4W group compared to respective matching placebo groups. Meanwhile, ongericimab also favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups.

Conclusions: Ongericimab administered at either 150 mg Q2W or 450 mg Q4W for 24 weeks, significantly reduced LDL-C levels and was well-tolerated in Chinese patients with HeFH.

Clinical trial registration: http://www.

Clinicaltrials: gov; Unique Identifier: NCT05325203.

Keywords: Heterozygous familial hypercholesterolemia; Lipid lowering therapy; Low density lipoprotein cholesterol; PCSK9.