Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome

ABSTRACT

Introduction: A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD)–familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy, and insulin resistance.

Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins, and insulin-sensitizing therapies depending on the extent of residual lipoprotein lipase (LPL) activity; novel therapies in development target triglyceride (TG)-rich lipoprotein particle clearance. Previously, a gene therapy approach to LPL-alipogene tiparvovec showed that direct targeting of LPL function reduced pancreatitis events. An antisense oligonucleotide to apolipoprotein-C3, volanesorsen has been shown to decrease TGs by 70–80% and possibly to reduce rates of pancreatitis admissions. Studies are underway to validate its long-term efficacy and safety. Other approaches investigating the role of LPL modulating proteins such as angiopoietin-like petide-3 (ANGPTL3) are under consideration.

Expert opinion: Current therapeutic options are not sufficient for management of many cases of FCS. The availability of antisense anti-apoC3 therapies and, in the future, ANGPTL3 therapies may remedy this.

KEYWORDS:

• Lipoprotein lipase deficiency
• familial chylomicronemia syndrome
• antibody therapy
• antisense oligonucleotide
• treatment

Declaration of interest

R Chaudhry has no conflicts of interest. A Viljoen has received travel support and/or served on speakers’ bureaus and/or advisory and/or involved in clinical trials funded by Amgen, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck Sharpe & Dohme, Napp, Novo Nordisk, and Sanofi-Aventis. AS Wierzbicki has been a clinical investigator for studies sponsored by Chiesi and Akcea. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.