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.