Safety and efficacy of therapies for chylomicronemia

Expert Rev Clin Pharmacol. 2022 Jun 28. doi: 10.1080/17512433.2022.2094768. Online ahead of print.ABSTRACTINTRODUCTION: Primary chylomicronemia is characterized by pathological accumulation of chylomicrons in plasma causing severe hypertriglyceridemia, typically >10 mmol/L (>875 mg/dL). Patients with the ultra-rare familial chylomicronemia syndrome (FCS) subtype completely lack lipolytic capacity and respond minimally to traditional triglyceride-lowering therapies. The mainstay of treatment is a low-fat diet, which is difficult to follow and compromises quality of life. New therapies are being developed primarily to prevent episodes of life-threatening acute pancreatitis.AREAS COVERED: Antagonists of apolipoprotein (apo) C-III, such as the antisense oligonucleotide (ASO) volanesorsen, significantly reduce triglyceride levels in chylomicronemia. However, approval of and access to volanesorsen are restricted since a substantial proportion of treated FCS patients developed thrombocytopenia. Newer apo C-III antagonists, namely the ASO olezarsen (formerly AKCEA-APOCIII-LRx) and short interfering RNA (siRNA) ARO-APOC3 appear to show efficacy with less risk of thrombocytopenia. Potential utility of antagonists of angiopoietin-like protein 3 (ANGPTL3) such as evinacumab and the siRNA ARO-ANG3 in subtypes of chylomicronemia remains to be defined.EXPERT OPINION: Emerging pharmacologic therapies for chylomicronemia show promise, particularly apo C-III antagonists. However, these t...
Source: Pharmacological Reviews - Category: Drugs & Pharmacology Authors: Source Type: research