Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia.

Abstract

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.

• Authors: Daniel N Ricotta, William Frishman
• Journal: Cardiology in review (Cardiol Rev) 2012 Mar-Apr Vol. 20 Issue 2 Pg. 90-5 ISSN: 1538-4683 [Electronic] United States
• PMID: 22293857 (Publication Type: Journal Article, Review)

Chemical References

• Anticholesteremic Agents
• Apolipoprotein B-100
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Oligonucleotides
• Oligonucleotides, Antisense
• mipomersen

Topics

• Administration, Cutaneous
• Anticholesteremic Agents (pharmacokinetics, pharmacology, therapeutic use)
• Apolipoprotein B-100 (antagonists & inhibitors)
• Cardiovascular Diseases (prevention & control)
• Clinical Trials as Topic
• Drug Administration Schedule
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypercholesterolemia (drug therapy)
• Oligonucleotides (pharmacokinetics, pharmacology, therapeutic use)
• Oligonucleotides, Antisense (pharmacokinetics, pharmacology, therapeutic use)