Efficacy and safety of recaticimab in lowering atherogenic lipids in patients with and without coronary artery disease: a patient-level pooled analysis

Background Patients with coronary artery disease (CAD) are at very high risk of recurrent cardiovascular events and require intensive lipid-lowering therapy to achieve guideline-recommended targets. Recaticimab is a long-acting anti-PCSK9 monoclonal antibody that has demonstrated significant lipid-lowering efficacy in patients with dyslipidaemia. However, whether its efficacy and safety differ according to CAD status remains uncertain. Purpose To investigate the efficacy and safety of recaticimab in patients with dyslipidaemia by CAD status. Methods This patient-level pooled analysis included patients with primary hypercholesterolaemia (non-familial and heterozygous) and mixed hyperlipaemia from four randomised controlled trials [three phase III (REMAIN 1-3) and one phase Ib/II]. Patients receiving approved dose regimens [recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or matching placebo] were analysed. Efficacy endpoints were set as the percentage change in LDL-C, non-HDL-C, and ApoB from baseline to Week 12 for the Q4W group, and to Week 16 for the Q8W group. Attainment of guideline-recommended lipid targets and safety were also assessed. Analyses were performed according to baseline CAD status. Results A total of 1120 patients were included, of whom 353 had CAD and 767 did not. Compared with patients without CAD, those with CAD were older (57 vs 47 years), more frequently male (72% vs 52%), and had lower baseline levels of LDL-C (2.7 vs 3.6 mmol/L), non-HDL-C (3.2 vs 4.1 mmol/L), and ApoB (0.97 vs 1.1 g/L). Patients with CAD received stable background statin therapy, whereas approximately two-thirds of patients without CAD received recaticimab as monotherapy. At Week 12/16, recaticimab significantly reduced LDL-C and other atherogenic lipids (non-HDL-C and ApoB) compared with placebo in both patients with and without CAD across both dosing regimens (Figure 1, all P<0.001). Among patients with CAD, 85.7% (Q4W) and 88.8% (Q8W) achieved LDL-C <1.8 mmol/L, whereas 89.4% (Q4W) and 89.8% (Q8W) of patients without CAD achieved LDL-C <2.6 mmol/L. In addition, 79.8% (Q4W) and 80.6% (Q8W) of patients with CAD receiving recaticimab achieved a >50% reduction from baseline in LDL-C. Similar high target attainment rates were observed for non-HDL-C and ApoB (Table 1). The incidence of treatment-related adverse events was 27.7% with recaticimab vs 24.3% with placebo in patients with CAD, and 21.4% with recaticimab vs 16.2% with placebo in patients without CAD, with most being mild. Conclusion Recaticimab demonstrated significant lipid-lowering efficacy, with high rates of guideline-recommended target attainment for atherogenic lipids, and a favourable safety profile in patients with dyslipidaemia, regardless of CAD status. These findings support its use in both CAD and non-CAD patients.Figure 1.Lipid-lowering efficacyTable 1.Lipid-lowering target attainment