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佐达西兰是一种RNAi治疗向ANGPTL3的药物,用于混合超脂血症

Robert S Rosenson¹, Daniel Gaudet¹, Robert A Hegele¹

¹From the Metabolism and Lipids Program, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York (R.S.R.); Université de Montréal, Montreal (D.G.), and Robarts Research Institute, London, ON (R.A.H.) - both in Canada; Baylor College of Medicine and the Texas Heart Institute - both in Houston (C.M.B.); Monash Victorian Heart Institute, Monash University, Melbourne, VIC (S.J.N.), and the School of Medicine, University of Western Australia, and the Department of Cardiology, Royal Perth Hospital, Perth (G.F.W.) - all in Australia; Lucas Research, Morehead City, NC (K.J.L.); and Arrowhead Pharmaceuticals, Pasadena, CA (J.S.M., R.Z., M.M., T.C., J.H.).

The New England journal of medicine

|May 29, 2024

概括

佐达西兰有效降低了混合高脂血症的成年人中的甘油三和胆固醇水平. 这种向ANGPTL3的RNA干扰疗法对治疗失脂症和心血管风险有很大的希望.

科学领域:

心血管医学心血管医学
遗传学遗传学是一个
药理学药理学是指药理学的学科.

背景情况:

血管蛋白样3 (ANGPTL3) 在脂质代谢中发挥关键作用,通过抑制脂酶和肝脏吸收富含甘油三蛋白的脂蛋白.
功能丧失的ANGPTL3突变与较低的脂质水平和降低动脉样硬化心血管疾病的风险有关.
佐达西兰是一种RNA干扰 (RNAi) 疗法,旨在减少肝脏中的ANGPTL3表达.

研究的目的:

评估成年混合多脂血症患者中佐达西兰的安全性和有效性.
评估佐达西兰对脂质水平和ANGPTL3表达的剂量依赖作用.

主要方法:

一个双盲,安慰剂控制,剂量范围的2b期试验.
204名患有混合性高脂血症的成年患者被随机分配给接受皮下佐达西兰 (50,100或200毫克) 或安慰剂.
治疗是在第1天和第12周进行的,随访持续到第36周. 主要终点是从基线到24周的甘油三水平的百分比变化.

主要成果:

与安慰剂 (P<0.001) 相比,Zodasiran在24周显示了对ANGPTL3水平和甘油三水平的实质性,剂量依赖的减少.
在非高密度胆固醇,阿波利波蛋白B和LDL胆固醇水平上也观察到显著的剂量依赖性下降.
在接受最高剂量的糖尿病患者中观察到糖化血红蛋白的暂时升高.

结论:

在24周后,Zodasiran治疗导致混合高脂血症患者的甘油三水平显著降低.
向ANGPTL3的RNAi疗法在治疗失脂症方面表现出有效性.
需要进一步研究zodasiran的长期安全性和有效性.

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