title: Mipomersen as a potential adjunctive therapy for hypercholesterolemia.
abstract: Mipomersen, an antisense oligonucleotide directed against apolipoprotein B-100 (apoB), was investigated for its safety and efficacy in reducing low-density lipoprotein (LDL) cholesterol (C) as adjunctive treatment for patients with homozygous familial hypercholesterolemia (HoFH) in a Phase III, double-blind, randomized, controlled trial. HoFH patients are very rare in the general population (∼ 1:1,000,000) and have very high risk for cardiovascular events. HoFH patients respond poorly to statins and most other existing lipid-lowering therapies. Mipomersen (200 or 160 mg) administered subcutaneously to 34 HoFH patients for 26 weeks significantly reduced LDL-C by 24.7% from baseline. In addition, mipomersen lowered plasma lipoprotein (a). In most patients, mipomersen administration was most associated with injection-site reactions; influenza-like symptoms were also more common in mipomersen-treated patients. Four patients had elevated serum alanine aminotransferase (ALT) concentrations, one of whom also had a significant increase in intrahepatic triglyceride content. Another patient met the stopping rules for increased ALT concentrations. No patient developed steatohepatitis during the study. Thus, so far short-term data indicate that mipomersen is safe and effective as an adjunctive drug for lowering LDL-C. Despite these promising results, the longer-term safety and efficacy of mipomersen still needs to be determined.
authors: University of Western Ontario, Robarts Research Institute, London, Ontario, Canada.
authors: Neeraj
authors: N
authors: Patel
authors: Robert A
authors: RA
authors: Hegele
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors* / Q000097:blood; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000592:standards*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000592:standards*; D004311:Double-Blind Method; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy; D017270:Lipoprotein(a) / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D009841:Oligonucleotides / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D009841:Oligonucleotides; C524142:mipomersen