Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
J Am Coll Cardiol. 2024 Nov 12;84(20):2026-2036. doi: 10.1016/j.jacc.2024.07.035. Epub 2024 Oct 9.
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 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.
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.
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%]).
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.
针对前蛋白转化酶枯草溶菌素 9（PCSK9）的单克隆抗体已被用于降低低密度脂蛋白胆固醇（LDL-C）水平，但需要每两周或每月给药一次。Recaticimab 是一种新型人源化单克隆抗体，专门针对 PCSK9，具有长效特性。
本研究旨在评估 recaticimab 单药治疗低至中度动脉粥样硬化性心血管疾病（ASCVD）风险的非家族性高胆固醇血症和混合性高脂血症患者的疗效和安全性，并探索不同的给药策略，为患者提供灵活的给药选择。
这是一项在中国 59 个地点进行的随机、双盲、安慰剂对照、3 期研究。空腹 LDL-C≥2.6 且<4.9mmol/L、空腹甘油三酯≤5.6mmol/L、10 年 ASCVD 风险评分<10%的患者按 2:2:2:1:1:1 的比例随机分配（2:2:2:1:1:1）接受皮下注射 recaticimab，剂量分别为每 4 周（Q4W）150mg、每 8 周（Q8W）300mg 和每 12 周（Q12W）450mg，或匹配的安慰剂，同时接受降脂饮食。主要终点是 150mg Q4W 和 450mg Q12W 治疗 12 周以及 300mg Q8W 治疗 16 周时 LDL-C 与基线相比的百分比变化。
共有 703 名患者接受了随机分组，并接受了 recaticimab（n=157、156 和 155，分别接受 150mg Q4W、300mg Q8W 和 450mg Q12W）或安慰剂（n=78、79 和 78，分别接受 150mg Q4W、300mg Q8W 和 450mg Q12W）治疗。与安慰剂相比，recaticimab 进一步将 LDL-C 降低了 49.6%（95%CI：44.2%-54.9%）（150mg Q4W）、52.8%（95%CI：48.3%-57.2%）（300mg Q8W）和 45.0%（95%CI：41.0%-49.0%）（450mg Q12W）（所有比较均<0.0001）。Recaticimab 的安全性与安慰剂相当。治疗 12 或 16 周后，接受 recaticimab 治疗的患者继续治疗至 24 周，而接受安慰剂治疗的患者则改用相同的给药策略。24 周 recaticimab 和 12 或 8 周 recaticimab 转换为安慰剂均有效。接受 24 周 recaticimab 治疗的患者最常见的治疗相关不良事件是注射部位反应（n=23[4.9%]）。
Recaticimab 单药治疗可显著降低 LDL-C 水平，与安慰剂相比，在低至中度 ASCVD 风险的非家族性高胆固醇血症和混合性高脂血症患者中具有相似的安全性，即使给药间隔长达 Q12W 也如此。
