April 3, 2022Open Access
View Full PaperSafety and efficacy of therapies for chylomicronemia
Key Result
Emerging pharmacologic therapies for chylomicronemia, particularly newer apo C-III antagonists, show promise in reducing triglycerides with potentially less risk of thrombocytopenia.
Structured PICO
Do emerging pharmacologic therapies (apo C-III and ANGPTL3 antagonists) reduce triglyceride levels and prevent acute pancreatitis in patients with primary chylomicronemia?
P
Population
Patients with primary chylomicronemia, including the ultra-rare familial chylomicronemia syndrome (FCS) subtype characterized by severe hypertriglyceridemia (>10 mmol/L or >875 mg/dL).
I
Intervention
Emerging pharmacologic therapies, particularly apolipoprotein (apo) C-III antagonists (volanesorsen, olezarsen, ARO-APOC3) and ANGPTL3 antagonists (evinacumab, ARO-ANG3).
O
Outcome
Reduction in triglyceride levels and prevention of life-threatening acute pancreatitis.surrogate
Emerging apo C-III antagonists show promise in reducing severe hypertriglyceridemia in chylomicronemia with potentially improved safety profiles compared to earlier agents.
Limitations
- 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
Abstract
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.