Emerging pharmacologic therapies for chylomicronemia, particularly newer apo C-III antagonists, show promise in reducing triglycerides with potentially less risk of thrombocytopenia.
Do emerging pharmacologic therapies (apo C-III and ANGPTL3 antagonists) reduce triglyceride levels and prevent acute pancreatitis in patients with primary chylomicronemia?
Emerging apo C-III antagonists show promise in reducing severe hypertriglyceridemia in chylomicronemia with potentially improved safety profiles compared to earlier agents.
INTRODUCTION: Primary chylomicronemia is characterized by pathological accumulation of chylomicrons in the 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 treatments are still investigational. Further study of their efficacy and safety in patients with both rare FCS and more common multifactorial chylomicronemia is needed.
Shamsudeen et al. (2022) conducted a review in Primary chylomicronemia and familial chylomicronemia syndrome (FCS). Apolipoprotein C-III antagonists and ANGPTL3 antagonists was evaluated. Emerging pharmacologic therapies for chylomicronemia, particularly newer apo C-III antagonists, show promise in reducing triglycerides with potentially less risk of thrombocytopenia.