Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial

European Heart Journal, 04/20/2012

The present data suggest that mipomersen is a potential therapeutic option in statin–intolerant patients at high risk for cardiovascular disease (CVD). The long–term follow–up of liver safety is required.

Methods

  • 33 subjects, not receiving statin therapy because of statin intolerance, received a weekly subcutaneous dose of 200 mg mipomersen or placebo (2:1 randomization) for 26 weeks.
  • The primary endpoint was per cent change in LDL cholesterol (LDL–c) from the baseline to Week 28.
  • The other efficacy endpoints were per cent change in apoB and lipoprotein a [Lp(a)].
  • Safety was determined using the incidence of treatment–emergent adverse events (AEs) and clinical laboratory evaluations.
  • After 26 weeks of mipomersen administration, LDL–c was reduced by 47 ± 18% (P < 0.001 vs. placebo). apoB and Lp(a) were also significantly reduced by 46 and 27%, respectively (P < 0.001 vs. placebo).
  • Four mipomersen (19%) and two placebo subjects (17%) discontinued dosing prematurely due to AEs.

Results

  • Persistent liver transaminase increases ≥3× the upper limit of normal were observed in seven (33%) subjects assigned to mipomersen.
  • In selected subjects, liver fat content was assessed, during and after treatment, using magnetic resonance spectroscopy.
  • Liver fat content in these patients ranged from 0.8 to 47.3%.
  • Liver needle biopsy was performed in two of these subjects, confirming hepatic steatosis with minimal inflammation or fibrosis.

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