title: Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy.
  
  
  RESULTS
  A planned interim analysis of an ongoing, open-label extension trial in patients (n = 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n = 130), 52 (n = 111), 76 (n = 66), and 104 (n = 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time.
  
  
  CONCLUSIONS
  Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations. CLINICALTRIALS.GOV: NCT00694109.
authors.affiliation: Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil raul.santos@incor.usp.br rdsf@uol.com.br.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Oregon Health and Science University, Portland, OR, USA.
authors.forename: P Barton
authors.initials: PB
authors.lastname: Duell
authors.affiliation: Soltero Cardiovascular Research Center Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Cara
authors.initials: C
authors.lastname: East
authors.affiliation: Duke University Medical Center, Durham, NC, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Guyton
authors.affiliation: Kansas University Atherosclerosis & LDL-Apheresis Center, Kansas City, KS, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Moriarty
authors.affiliation: Genzyme Corporation, Cambridge, MA, USA.
authors.forename: Wai
authors.initials: W
authors.lastname: Chin
authors.affiliation: Genzyme Corporation, Cambridge, MA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mittleman
mesh_terms: D000279:Administration, Cutaneous; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016632:Apolipoprotein A-I / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism; D057915:Drug Substitution; D005260:Female; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018570:Risk Assessment; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D017270:Lipoprotein(a); D009841:Oligonucleotides; D014280:Triglycerides; C524142:mipomersen
keywords: Adverse events; Familial hypercholesterolaemia; Hypercholesterolaemia; Lipid-lowering; Long-term safety