title: 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.affiliation: Departments of Medicine, Harvard Medical School/Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Ricotta
authors.forename: William
authors.initials: W
authors.lastname: Frishman
mesh_terms: D000279:Administration, Cutaneous; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000037:antagonists & inhibitors*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D009841:Oligonucleotides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C524142:mipomersen