Recaticimab Monotherapy for NonfamilialHypercholesterolemia andMixed Hyperlipemia: ThePhase 3 REMAIN-1 Randomized Trial.

Abstract

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. The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patientswith 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. 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<4.9mmol/L, fasting triglyceride≤5.6mmol/L, and 10-year ASCVD risk score<10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150mg every 4weeks (Q4W), 300mg every 8weeks (Q8W), or 450mg every 12weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150mg Q4W and 450mg Q12W and to week 16 for 300mg Q8W. A total of 703 patients underwent randomization and received recaticimab (n=157, 156, and 155 for 150mg Q4W, 300mg Q8W, and 450mg 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 150mg Q4W, 52.8% (95%CI: 48.3%-57.2%) at 300mg Q8W, and 45.0% (95%CI: 41.0%-49.0%) at 450mg Q12W (P< 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16weeks 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 24weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). 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.