INTRODUCTION: Severe hypertriglyceridemia (sHTG) is a complex disorder of lipid 
metabolism characterized by plasma levels of triglyceride (TG) greater than 885 
mg/dl (>10 mmol/L). The treatment of sHTG syndromes is challenging because 
conventional treatments are often ineffective in reducing TG under the threshold 
to prevent acute pancreatitis (AP). The inhibition of APOC3, which encodes a 
protein involved in triglyceride (TG)-rich lipoproteins (TGRLs) removal, has 
been reported to be a novel target for the treatment of sHTG. Volanesorsen is a 
second-generation antisense oligonucleotide inhibiting apoC-III 
transcription/translation that has been recently approved in Europe for Familial 
Chylomicronemia Syndrome (FCS) treatment.
AREAS COVERED: This review summarizes the evidences on the efficacy and safety 
of volanesorsen for the treatment of sHTG syndromes.
EXPERT OPINION: Volanesorsen effectively reduces TG in sHTG through a mechanism 
that is mainly LPL-independent, potentially decreasing the risk of AP. Some 
safety concerns have been raised with the use of volanesorsen, mainly 
represented by the occurrence of thrombocytopenia. Due to the potential severity 
of side effects, some caution is needed before affirming the long-term utility 
of this drug. Despite this, volanesorsen currently remains the only drug that 
has been demonstrated effective in FCS, which otherwise remains an untreatable 
disease.