Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased
risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism
of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene
encoding apoC-III (APOC3) is associated with low triglyceride levels and a decreased risk for
cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia.
Although many drugs such as fibrates, statins and omega-3 fatty acids modestly
decrease triglyceride levels (and apoC-III concentrations), there are many patients who
still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially
for CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously
called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both,
apoC-III production and triglyceride concentrations and is being currently evaluated in phase
3 trials. In this narrative review, we present the currently available clinical evidence on the
efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
Keywords: Antisense oligonucleotides, apolipoprotein C-III, hypertriglyceridemia, IONIS-ApoCIIIRx, ISIS
304801, ISIS-ApoCIIIRx, triglycerides, volanesorsen.
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