Recaticimab Monotherapy for Nonfamilial Hypercholesterolemia and Mixed Hyperlipemia

BACKGROUND Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been used to reduce the level of low-density lipoprotein cholesterol (LDL-C), but require either biweekly or monthly dosing frequency. Recaticimab is a new humanized monoclonal antibody selectively targeting PCSK9, with long-acting characteristic. OBJECTIVES The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk, and to explore different dosing strategies to provide patients with flexible administration options. METHODS This was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 59 sites in China. Patients with fasting LDL-C >= 2.6 to <4.9 mmol/L, fasting triglyceride <= 5.6 mmol/L, and 10-year ASCVD risk score <10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg every 12 weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150 mg Q4W and 450 mg Q12W and to week 16 for 300 mg Q8W. RESULTS A total of 703 patients underwent randomization and received recaticimab (n = 157, 156, and 155 for 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W, respectively) or placebo (n = 78, 79, and 78, respectively). Compared with placebo, recaticimab further reduced LDL-C by 49.6% (95% CI: 44.2%-54.9%) at 150 mg Q4W, 52.8% (95% CI: 48.3%57.2%) at 300 mg Q8W, and 45.0% (95% CI: 41.0%-49.0%) at 450 mg Q12W (P < 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16 weeks of treatment, patients who received recaticimab continued treatment until week 24, whereas those allocated to placebo were switched to recaticimab treatment with the same dosing strategy. Both 24-week recaticimab and 12- or 8-week recaticimab switched from placebo were effective. With 24 weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). CONCLUSIONS Recaticimab monotherapy yielded significant LDL-C reductions and showed comparable safety vs placebo in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate ASCVD risk, even with an infrequent dosing interval up to Q12W.