Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Faculty of Medicine and University Hospital, Kerpener Str. 6, 50937, Cologne, Germany.
Department of Internal Medicine and Geriatrics, Bethel Clinic (EvKB) and Medical School EWL, University of Bielefeld, Bielefeld, Germany.
Curr Atheroscler Rep. 2023 Oct;25(10):701-709. doi: 10.1007/s11883-023-01140-z. Epub 2023 Aug 29.
To provide an insight into the new pharmacological options for the treatment of severe hypertriglyceridemia (sHTG).
sHTG is difficult to treat. The majority of the traditional pharmacological agents available have limited success in both robustly decreasing triglyceride levels and/or in reducing the incidence of acute pancreatitis (AP), the most severe complication of sHTG. Therapeutic options with novel mechanisms of action have been developed, such as antisense oligonucleotides (ASO) and small interfering RNA (siRNA) targeting APOC3 and ANGPTL3. The review discusses also 2 abandoned drugs for sHTG treatment, evinacumab and vupanorsen. The ASO targeting APOC3, volanesorsen, is approved for use in patients with familial chylomicronemia syndrome (FCS) in Europe. Olezarsen, an N-acetylgalactosamine (GalNAc)-conjugated ASO with the same target, seems to have a better safety and efficacy profile. siRNA targeting APOC3 and ANGPTL3, namely ARO-APOC3 and ARO-ANG3, are also promising for the treatment of sHTG. However, the ultimate clinical goal of any sHTG treatment, the decrease in the risk of AP, has not been definitively achieved till now by any pharmacotherapy, either approved or in development.
提供对严重高甘油三酯血症（sHTG）治疗新的药理学选择的深入了解。
sHTG 难以治疗。大多数现有的传统药物在强效降低甘油三酯水平和/或降低 sHTG 最严重并发症急性胰腺炎（AP）的发生率方面都只有有限的成功。已经开发出具有新型作用机制的治疗选择，例如针对 APOC3 和 ANGPTL3 的反义寡核苷酸（ASO）和小干扰 RNA（siRNA）。本文还讨论了两种用于 sHTG 治疗的已放弃药物，evinacumab 和 vupanorsen。针对 APOC3 的 ASO，即 volanesorsen，已在欧洲获得用于治疗家族性乳糜微粒血症综合征（FCS）的批准。具有相同靶标的 N-乙酰半乳糖胺（GalNAc）缀合 ASO，olezarsen，似乎具有更好的安全性和疗效特征。针对 APOC3 和 ANGPTL3 的 siRNA，即 ARO-APOC3 和 ARO-ANG3，也有望用于治疗 sHTG。然而，迄今为止，任何批准或正在开发的药物治疗都没有最终实现 sHTG 治疗的最终临床目标，即降低 AP 的风险。
