title: Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia.
abstract: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE).
  
  
  
  Seven patients aged 12-18 years were randomized to 200-mg mipomersen or placebo weekly (26 weeks) and received mipomersen in the OLE (52 or 104 weeks). Plasma LDL-C and apo B concentrations and adverse events were assessed.
  
  
  
  All pediatric patients completed the RCT and entered OLE. The 3 mipomersen patients in the RCT experienced mean reductions from baseline to RCT end of 42.7% and 46.1% for LDL-C and apo B, respectively. Of the 4 placebo patients, 3 responded well to mipomersen during OLE, with reductions in LDL-C of 26.5%-42.1%. Three patients completed OLE treatment, and 4 patients discontinued therapy due to adverse events. Lipid level fluctuations were observed and were likely due to poor compliance.
  
  
  
  Long-term mipomersen treatment was successful regarding efficacy parameters for pediatric HoFH patients. The safety profile was consistent with other phase 3 clinical trials. Long-term compliance was an issue. Measures supporting adherence should be encouraged.
authors: Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: frederick.raal@wits.ac.za.
authors: Frederick J
authors: FJ
authors: Raal
authors: Department of Vascular Medicine AMC, AZ Amsterdam, Netherlands; Department of Pediatrics Emma Children's Hospital AMC, AZ Amsterdam, Netherlands.
authors: Marjet J
authors: MJ
authors: Braamskamp
authors: Medical Communications, Sanofi Genzyme, Cambridge, MA, USA.
authors: Sheryl L
authors: SL
authors: Selvey
authors: Biostatistics and Programming, Sanofi Genzyme, Cambridge, MA, USA.
authors: Charlotte H
authors: CH
authors: Sensinger
authors: Department of Vascular Medicine AMC, AZ Amsterdam, Netherlands.
authors: John J
authors: JJ
authors: Kastelein
mesh_terms: D000293:Adolescent; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004347:Drug Interactions; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D009841:Oligonucleotides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012449:Safety
chemical_list: D000924:Anticholesteremic Agents; D009841:Oligonucleotides; C524142:mipomersen
keywords: Cholesterol; Hypercholesterolemia; Lipoproteins; Mipomersen; Pediatrics