Early Investigational and Experimental Therapeutics for the Treatment of Hypertriglyceridemia.

Ioannis Parthymos,Matilda Florentin,Michael S Kostapanos,George Liamis

doi:10.3390/jcdd9020042

Abstract

Hypertriglyceridemia has been identified as a risk factor for cardiovascular disease and acute pancreatitis. To date, there are only few drug classes targeting triglyceride levels such as fibrates and ω-3 fatty acids. These agents are at times insufficient to address very high triglycerides and the residual cardiovascular risk in patients with mixed dyslipidemia. To address this unmet clinical need, novel triglyceride-lowering agents have been in different phases of early clinical development. In this review, the latest and experimental therapies for the management of hypertriglyceridemia are presented. Specifically, ongoing trials evaluating novel apolipoprotein C-III inhibitors, ω-3 fatty acids, as well as fibroblast growth 21 analogues are discussed.

Highlights

Investigational and ExperimentalHypertriglyceridemia, defined as triglycerides (TG) > 150 mg/dL (1.7 mmol/L), may be primary due to genetic disorders, or secondary in the context of other diseases, such diabetes mellitus (DM), alcoholism, chronic kidney disease, and endocrine disorders [1].The risk for acute pancreatitis increases progressively with serum TG levels over 500 mg/dL (5.6 mmol/L) and more markedly with levels over 1000 mg/dL (11.3 mmol/L), whilst lower TG levels are encountered in atherogenic dyslipidemia and are associated with enhanced cardiovascular (CV) risk [2,3]
In the REDUCE-IT study, icosapent ethyl administration was associated with a significantly reduced risk for CV disease (CVD) by 22% compared with the placebo in individuals with established CVD or with DM and other CV risk factors [34]
Elevated circulating TGs increase the risk of CVD even in statin-treated patients, while individuals with excessive hypertriglyceridemia may suffer from severe acute pancreatitis

Summary

Introduction

Hypertriglyceridemia, defined as triglycerides (TG) > 150 mg/dL (1.7 mmol/L), may be primary due to genetic disorders, or secondary in the context of other diseases, such diabetes mellitus (DM), alcoholism, chronic kidney disease, and endocrine disorders [1]. The safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of scARO-APOC3 are being evaluated in a phase one trial of healthy individuals, patients with hypertriglyceridemia (TG > 300 mg/dL; 3.38 mmol/L), and patients with a diagnosis of FCS (n = 112 participants). The primary outcome of the study is any reported adverse event within 4 weeks [37] In another randomized, double-blind, placebo-controlled, phase three study, the safety and efficacy of MAT900, an investigational omega-3 FA predominantlycontaining EPA and docosapentaenoic acid 1, will be evaluated in 300 individuals with fasting triglyceridelevels. In a phase two, randomized, double-blind, placebo-controlled trial, the efficacy and safety of BIO89-100 administrated sc weekly or every two weeks in 90 individuals with severe hypertriglyceridemia (TG > 500/1.7 mmol/L and

Pemafibrate

Findings

Conclusions