Efficacy and safety of Ongericimab in patients with hypercholesterolemia: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: < 0.00001

• Effect Size: MD -69.48% for 150mg Q2W regimen

• Primary Outcome: LDL-C reduction ranging from 61.82% to 73.11% across dosing regimens

• Nnt Or Sensitivity: Clinically significant LDL-C reduction >50% in all patients based on effect sizes

• Confidence Interval: 95% CI: -73.02 to -65.94

Clinical Application

Requires specialist initiation and PBS authority approval for PCSK9 inhibitors Would align with RACGP lipid management guidelines and PBS criteria for PCSK9 inhibitors in high-risk cardiovascular patients Australian patients with hypercholesterolemia inadequately controlled on maximum tolerated statin therapy

Abstract

BACKGROUND: Hypercholesterolemia represents abnormally elevated cholesterol levels and constitutes a major modifiable risk factor for cardiovascular diseases (CVDs). Low-density lipoprotein cholesterol (LDL-C) reduction remains the primary therapeutic target. However, many high-risk patients fail to achieve recommended LDL-C targets with conventional lipid-lowering therapies. Ongericimab is a new humanized recombinant monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). We aimed to evaluate the efficacy and safety of Ongericimab compared to placebo in patients with hypercholesterolemia. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Cochrane Library, Web of Science and Google Scholar through February 2025 for randomized controlled trials (RCTs) comparing Ongericimab versus placebo. Outcomes were pooled as mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) using random-effects models. RESULTS: Five RCTs comprising 1421 patients were included. Ongericimab significantly reduced LDL-C across all dosing regimens: 150 mg every 2 weeks (MD -69.48%, 95% CI: -73.02 to -65.94), 300 mg every 4 weeks (MD -61.82%, 95% CI: -66.66 to -56.98), and 450 mg every 4 weeks (MD -73.11%, 95% CI: -89.56 to -56.65); all p < 0.00001. Significant reductions were also observed in lipoprotein(a) (MD range: -44.81% to -50.06%), apolipoprotein B, non-HDL cholesterol, triglycerides, and total cholesterol, along with significant increases in HDL cholesterol and apolipoprotein A1. Adverse event rates were comparable between groups, with a pooled reduction OR of 0.85 (95% CI: 0.73-0.99) for overall treatment-emergent adverse events, favoring Ongericimab. CONCLUSION: This meta-analysis demonstrates that Ongericimab is effective and safe for improving lipid parameters in patients with hypercholesterolemia and dyslipidemia. These findings support Ongericimab as a valuable therapeutic option for patients requiring additional LDL-C reduction beyond conventional therapy. Further long-term studies are recommended to confirm cardiovascular outcomes.

References

1. 1.Youseif, A. L., Younis, A. F., Elmezayen, Z. W., Eldahrawy, M., Hammad, N., Hamed, B. M., Saleh, A. R., Mohamed, A. A., Saad, O. A., Ramadan, A. M., & Awad, A. A. (2026). Efficacy and safety of Ongericimab in patients with hypercholesterolemia: a systematic review and meta-analysis. European Journal of Clinical Pharmacology. https://doi.org/10.1056/NEJMoa1501031