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Apolipoprotein B synthesis inhibition: results from clinical trials

Visser, Maartje E; Kastelein, John JP; Stroes, Erik SG

doi: 10.1097/MOL.0b013e32833af4c1
Hyperlipidaemia and cardiovascular disease: Edited by Paul N. Durrington

Purpose of review Mipomersen is a second-generation antisense oligonucleotide developed to inhibit the synthesis of apolipoprotein B-100 in the liver. In this review we will summarize the results of recent preclinical and clinical studies addressing safety and low-density lipoprotein-cholesterol (LDL-c) lowering efficacy of this new compound.

Recent findings In phase 3 clinical trials, mipomersen has been shown to significantly reduce LDL-c in patients with homozygous and heterozygous familial hypercholesterolemia on maximally tolerated lipid-lowering therapy. Injection site reactions, flu-like symptoms and increases in liver transaminases were the main adverse events. A recent safety study, designed to investigate the effects of mipomersen on intrahepatic triglyceride content, failed to show evidence of clinically relevant hepatic steatosis after 13 weeks of treatment.

Summary Mipomersen is a new agent to lower LDL-c in patients at increased risk of cardiovascular disease and/or intolerant to statins. Whereas safety concerns have focused on hepatic fat accumulation, to date no evidence of clinically relevant increases of intrahepatic triglyceride content are reported. Ongoing and future studies are eagerly awaited to assess the impact of mipomersen on hepatic triglyceride content after prolonged exposure.

Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands

Correspondence to Erik S.G. Stroes, MD, PhD, Department of Vascular Medicine, AMC, Room F4.159–2, Meibergdreef 9, PO box 22660, 1100 DD Amsterdam, The Netherlands Tel: +31 20 5666612; fax: +31 20 5669343; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.