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通过单克隆抗体抑制血管类蛋白3可降低高甘油三
Zahid Ahmad1, Poulabi Banerjee2, Sara Hamon2
1Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas (Z.A.).
Circulation
|June 28, 2019
概括
在两项第一阶段研究中,Evinacumab是一种ANGPTL3抑制剂,有效降低过高甘油脂水平. 这种药物耐受性很好,
科学领域:
- 药理学和治疗学
- 心血管医学
- 脂肪新陈代谢
背景情况:
- 过高血糖是心血管疾病的重要危险因素,通常与脂蛋白清除受损有关.
- 血管蛋白样蛋白3 (ANGPTL3) 通过抑制脂蛋白脂酶发挥关键作用,从而增加甘油三水平.
- 在之前的研究中,针对性ANGPTL3抑制剂Evinacumab在降低甘油三方面表现有前途.
研究的目的:
- 评估埃维纳库马布的安全性,耐受性和有效性.
- 评估埃维纳库马布对甘油三和其他脂质水平的剂量依赖作用.
- 在两项第一阶段临床研究中,比较埃维纳库马布与安慰剂的效果.
主要方法:
- 进行了两个随机的,安慰剂控制的第一阶段研究 (单剂量上升 (SAD) 和多剂量上升 (MAD)).
- 参与者 (n=83在SAD中,n=56在MAD中) 的甘油三位数在150- 450 mg/ dL之间,LDL胆固醇≥100 mg/ dL.
- 以不同的剂量和频率通过皮下或静脉注射,并对不良事件和脂质状况进行监测.
主要成果:
- 埃维纳库马布的耐受性一般很好,没有报告严重的不良反应或停止治疗.
- 观察到剂量依赖的甘油三降低,最大降低为76. 9% (SAD) 和83. 1% (MAD) 静脉注射.
- 肝酶和肌酸酶的暂时升高,但与剂量无关或不严重.
结论:
- 埃维纳库马布在过高甘油症患者中表现出良好的安全性和显著的降甘油效果.
- 观察到的脂质变化与与降低心血管风险相关的ANGPTL3功能丧失突变相一致.
- 用埃维纳库马布抑制ANGPTL3是一种有前途的治疗策略,可以治疗高甘油度,并可能改善心血管结果.
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