Abstract 10921: Efficacy and Safety of Ongericimab in Chinese Patients With Homozygous Familial Hypercholesterolemia

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Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder with extremely high low-density lipoprotein cholesterol (LDL-C) levels that contributes to atherosclerotic cardiovascular disease and death, even in adolescent. Ongericimab, a monoclonal antibody against human proprotein convertase subtilisin/kexin type 9 (PCSK9), inhibits PCSK9-mediated degradation of LDL receptor (LDLR), and reduces LDL-C by 58.3-66.5% in Chinese patients with hyperlipidemia. Due to the high genetic heterogeneity of HoFH, the LDL-C lowering effect of Ongericimab remains elusive in Chinese population. This is the first study to assess the efficacy and safety of anti-PCSK9 antibody in Chinese patients with HoFH. Methods: This is a single arm, open-label phase 2 study. 31 patients (aged ≥12 years) with HoFH diagnosed by clinical or genetic criteria, on stable lipid-lowering therapies for ≥4 weeks, were enrolled to receive subcutaneous Ongericimab 450 mg every 4 weeks for 52 weeks. The primary endpoint was percentage change in LDL-C from baseline at week 12. Results: At the time of this interim analysis, 30 out of 31 patients completed 12 weeks treatment. All patients were on statins (77.4% on high intensity statin) and the mean (SD) baseline LDL-C was 8.6 (3.1) mmol/L. The least squares mean percentage change in LDL-C from baseline was -12.6% (95% CI: -19.7%, -5.6%; p=0.001) at week 12. Further analysis based on residual LDLR activity, the mean (SD) LDL-C change from baseline was -21.7 (28.0)% in 14 patients with defective LDLR (at least one defective allele) and -1.4 (9.6)% in 7 patients with negative LDLR (at least one negative allele), respectively (Figure 1). No serious side effects were reported. Conclusion: Ongericimab was well tolerated and significantly reduced LDL-C levels in Chinese patients with HoFH. Patients with defective LDLR demonstrated better response than those with negative LDLR.