抑制Angiopoietin-Like蛋白质与单克隆抗体3减少甘油三酯高甘油三酯血症。

文章的细节

引用

复制到剪贴板

Banerjee Ahmad Z, P,亨茂年代,陈KC, Bouzelmat, Sasiela WJ, Pordy R,阵线,Dansky H, Gipe哒,邓巴RL

抑制Angiopoietin-Like蛋白质与单克隆抗体3减少甘油三酯高甘油三酯血症。

循环。2019年8月6日,140 (6):470 - 486。doi: 10.1161 / CIRCULATIONAHA.118.039107。Epub 2019年6月27日。

PubMed ID

31242752 (在PubMed

]

文摘

背景:高甘油三酯血症与心血管风险增加,可能是由于脂蛋白清除受损。Angiopoietin-like蛋白3 (ANGPTL3)抑制脂蛋白脂肪酶活性,增加甘油三酯和其他脂质。Evinacumab ANGPTL3抑制剂,减少甘油三酯在健康志愿者和纯合子家族性hypercholesterolemic个人。结果从2 hypertriglyceridemic科目的第一阶段研究报告。方法:受试者甘油三酯> 150 / = 100 mg / dL (n = 83单一剂量提升研究[难过];n = 56为多个提升剂量研究[疯狂])随机3:1 evinacumab:安慰剂。悲伤的话题收到evinacumab 75/150/250 mg皮下注射,或静脉注射5/10/20毫克/公斤,监控126天。疯狂的对象收到evinacumab每周在150/300/450 mg皮下注射一次,300/450毫克每2周,或静脉注射20毫克/公斤每隔4周和6个月的随访中56天。主要的结果是治疗诱发的不良事件的发生率和严重程度。功效分析包括甘油三酯的变化随着时间的推移和其他脂质。 RESULTS: In the SAD, 32 (51.6%) versus 9 (42.9%) subjects on evinacumab versus placebo reported treatment-emergent adverse events. In the MAD, 21 (67.7%) versus 9 (75.0%) subjects on subcutaneously evinacumab versus placebo and 6 (85.7%) versus 1 (50.0%) on intravenously evinacumab versus placebo reported treatment-emergent adverse events. No serious treatment-emergent adverse events or events leading to death or treatment discontinuation were reported. Elevations in alanine aminotransferase (7 [11.3%] SAD), aspartate aminotransferase (4 [6.5%] SAD), and creatinine phosphokinase (2 [3.2%) SAD, 1 [14.3%] MAD) were observed with evinacumab (none in the placebo groups), which were single elevations and were not dose-related. Dose-dependent reductions in triglycerides were observed in both studies, with maximum reduction of 76.9% at day 3 with 10 mg/kg intravenously (P<0.0001) in the SAD and of 83.1% at day 2 with 20 mg/kg intravenously once every 4 weeks (P=0.0003) in the MAD. Significant reductions in other lipids were observed with most evinacumab doses versus placebo. CONCLUSION: Evinacumab was well-tolerated in 2 Phase 1 studies. Lipid changes in hypertriglyceridemic subjects were similar to those observed with ANGPTL3 loss-of-function mutations. Because the latter is associated with reduced cardiovascular risk, ANGPTL3 inhibition may improve clinical outcomes. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifiers: NCT01749878 and NCT02107872.

DrugBank数据引用了这篇文章

药物

Evinacumab