昂戈瑞西单抗在中国他汀不耐受的原发性高胆固醇血症或混合性血脂异常患者中的疗效和安全性：一项随机、安慰剂对照的3期试验。
Efficacy and safety of ongericimab in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia: a randomized, placebo-controlled phase 3 trial.
作者信息
Shao Chunli, Zhang Shu, Cheng Zhifeng, Yang Keping, Wang Gaopin, Shi Xiaoxia, Yang Haibo, Ji Yuan, Li Hua, Zhang Shanchun, Ma Jinxia, Pei Zhaohui, Zhang Yumin, Li Yang, Li Lipeng, Zheng Yang, Shao Cong, Zhang Mengqi, Hao Yu, Tang Yi-da
机构信息
Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
Department of Cardiology, Daqing People's Hospital, Daqing, China.
出版信息
Atherosclerosis. 2025 Jun 16;407:120408. doi: 10.1016/j.atherosclerosis.2025.120408.
BACKGROUND AND AIMS
Several protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in statin-intolerant patients, but none have been verified in Chinese patients. This study aimed to evaluate the efficacy and safety of ongericimab, a novel PCSK9 monoclonal antibody, in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia.
METHODS
This was a randomized, multicenter, double-blind, placebo-controlled phase 3 study designed to enroll 120 statin-intolerant adult patients. Eligible patients were randomly assigned in a 2:1 ratio to receive ongericimab 150 mg or placebo subcutaneously every 2 weeks for 12 weeks in the double-blind treatment period, followed by 40 weeks of ongericimab treatment during the open-label period. The primary endpoint was a percentage change in LDL-C from baseline to week 12. The key secondary endpoints included percentage change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC), and lipoprotein(a) [Lp(a)].
RESULTS
From February 6, 2023, to September 23, 2024, a total of 139 patients were enrolled. The least-squares (LS) mean difference between ongericimab and placebo groups in LDL-C from baseline to week 12 was -66.2 % (95 % CI: 74.2 %, -58.2 %; p < 0.0001), with reductions sustained up to week 52. Ongericimab also significantly reduced levels of non-HDL-C, ApoB, TC, and Lp(a). The overall incidence of treatment-emergent adverse events was comparable between the ongericimab and placebo groups.
CONCLUSION
Ongericimab significantly reduced LDL-C as well as other atherogenic lipid levels and was well tolerated in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia.
CLINICAL TRIAL REGISTRATION
CLINICALTRIALS
gov; Unique Identifier: NCT05621070.
背景与目的
几种9型前蛋白转化酶枯草溶菌素/克新蛋白酶（PCSK9）抑制剂已被证明可显著降低他汀类药物不耐受患者的低密度脂蛋白胆固醇（LDL-C）水平，但在中国患者中尚未得到验证。本研究旨在评估新型PCSK9单克隆抗体昂戈瑞西单抗在中国他汀类药物不耐受的原发性高胆固醇血症或混合性血脂异常患者中的疗效和安全性。
方法
这是一项随机、多中心、双盲、安慰剂对照的3期研究，旨在招募120名他汀类药物不耐受的成年患者。符合条件的患者以2:1的比例随机分配，在双盲治疗期每2周皮下注射150 mg昂戈瑞西单抗或安慰剂，共12周，随后在开放标签期进行40周的昂戈瑞西单抗治疗。主要终点是从基线到第12周LDL-C的百分比变化。关键次要终点包括从基线到第12周非高密度脂蛋白胆固醇（non-HDL-C）、载脂蛋白B（ApoB）、总胆固醇（TC）和脂蛋白(a) [Lp(a)]的百分比变化。
结果
从2023年2月6日至2024年9月23日，共招募了139名患者。昂戈瑞西单抗组与安慰剂组从基线到第12周LDL-C的最小二乘（LS）平均差异为-66.2%（95%CI：-74.2%，-58.2%；p<0.0001），降低效果持续至第52周。昂戈瑞西单抗还显著降低了non-HDL-C、ApoB、TC和Lp(a)的水平。昂戈瑞西单抗组与安慰剂组治疗中出现的不良事件总体发生率相当。
结论
昂戈瑞西单抗显著降低了LDL-C以及其他致动脉粥样硬化血脂水平，在中国他汀类药物不耐受的原发性高胆固醇血症或混合性血脂异常患者中耐受性良好。
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