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

• Published in: Expert opinion on pharmacotherapy Vol. 21; no. 14; p. 1675
• Main Authors: D'Erasmo, Laura, Gallo, Antonio, Di Costanzo, Alessia, Bruckert, Eric, Arca, Marcello
• Format: Journal Article
• Language: English
• Published: England 21.09.2020
• Subjects: Apolipoprotein C-III - antagonists & inhibitors; Europe; Humans; Hyperlipoproteinemia Type I - drug therapy; Hypertriglyceridemia - blood; Hypertriglyceridemia - drug therapy; Hypertriglyceridemia - metabolism; Lipoproteins - blood; Oligonucleotides - administration & dosage; Oligonucleotides - adverse effects; Oligonucleotides - therapeutic use; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - adverse effects; Oligonucleotides, Antisense - therapeutic use; Pancreatitis - chemically induced; Pancreatitis - prevention & control; Thrombocytopenia - chemically induced; Thrombocytopenia - prevention & control; Triglycerides - blood; Europe; volanesorsen; treatment; Apo c-III; orphan drug; antisense oligonucleotides; familial chylomicronemia syndrome; clinical trials; severe hypertriglyceridemia
• ISSN: 1744-7666
• DOI: 10.1080/14656566.2020.1787380

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 , 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. This review summarizes the evidences on the efficacy and safety of volanesorsen for the treatment of sHTG syndromes. 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.