Abstract
BackgroundRecaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia.MethodsIn this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule).ResultsA total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from −48.37 to −59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase.ConclusionRecaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo.Trial registrationClinicalTrials.gov, number NCT03944109
Highlights
Recaticimab (SHR-1209, a humanized monoclonal antibody against Proprotein convertase subtilisin/kexin type 9 (PCSK9)) showed robust low-density lipoprotein-cholesterol (LDL-C) reduction in healthy volunteers
Baseline characteristics were generally similar between the recaticimab groups and the placebo group, except a little higher proportion of females in the placebo group (Additional file: Table S1)
It has been reported that treatment with atorvastatin increases the level of plasma PCSK9, which partly explained why increasing statin doses only led to diminished reduction in LDL-C level [22, 23]
Summary
Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. Hypercholesterolemia, a common disorder characterized by an elevated plasma concentration of low-density lipoprotein-cholesterol (LDL-C), is one of the predominant causes for atherosclerosis and, cardiovascular disease. Reducing the level of LDL-C remains the cornerstone of hypercholesterolemia management and atherosclerotic cardiovascular disease prevention [1, 2]. Statins that work as cholesterol-synthesis inhibitors are widely prescribed lipid-lowering drugs, with approximately 20 to 65% reduction in the LDL-C level [4]. The addition of gut-acting drugs (bile acid sequestrants or ezetimibe) to a statin regimen only produces an additional 13 to 30% reduction in LDL-C, and bile acid sequestrants are associated with headaches and gastrointestinal complaints, which limit their practical use [2]
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