Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

Raul D. Santos, P. Barton Duell, Cara East, John R. Guyton, Patrick M. Moriarty, Wai Chin, Robert S. Mittleman

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)566-575
Number of pages10
JournalEuropean heart journal
Issue number9
StatePublished - Mar 1 2015


  • Adverse events
  • Familial hypercholesterolaemia
  • Hypercholesterolaemia
  • Lipid-lowering
  • Long-term safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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