Evaluation of efficacy and safety of antisense inhibition of apolipoprotein C-III with volanesorsen in patients with severe hypertriglyceridemia.

Abstract

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.

• Authors: Laura D'Erasmo, Antonio Gallo, Alessia Di Costanzo, Eric Bruckert, Marcello Arca
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 21 Issue 14 Pg. 1675-1684 (Oct 2020) ISSN: 1744-7666 [Electronic] England
• PMID: 32646313 (Publication Type: Journal Article, Review)

Chemical References

• Apolipoprotein C-III
• ISIS 304801
• Lipoproteins
• Oligonucleotides
• Oligonucleotides, Antisense
• Triglycerides
• lipoprotein triglyceride

Topics

• Apolipoprotein C-III (antagonists & inhibitors)
• Europe
• Humans
• Hyperlipoproteinemia Type I (drug therapy)
• Hypertriglyceridemia (blood, drug therapy, metabolism)
• Lipoproteins (blood)
• Oligonucleotides (administration & dosage, adverse effects, therapeutic use)
• Oligonucleotides, Antisense (administration & dosage, adverse effects, therapeutic use)
• Pancreatitis (chemically induced, prevention & control)
• Thrombocytopenia (chemically induced, prevention & control)
• Triglycerides (blood)