Mipomersen Shows Promise in Treating High Cholesterol

Strategic Insights -

Mipomersen, an experimental therapy, has demonstrated significant reductions in low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) levels in patients with familial hypercholesterolemia (FH). These results were presented at the 79th European Atherosclerosis Society (EAS) Congress, where two phase 3 studies showed that mipomersen effectively lowered Lp(a) levels, an independent risk factor for heart disease, in patients with HeFH and high baseline Lp(a). The studies also met all primary, secondary, and tertiary endpoints, and most patients had elevated Lp(a) levels at baseline.

Key Takeaways:

  • Mipomersen decreased LDL-C by 28 and 36 percent compared to increases of 5 and 13 percent for placebo in two separate phase 3 trials in patients with HeFH.
  • Mipomersen reduced Lp(a) by a median 21 and 39 percent compared to zero and five percent for placebo, respectively, in the same trials.
  • In one of the trials, mipomersen reduced the percentage of patients with LDL-C levels ≥ 160 mg/dL by 95%, from 39% to 2%.
  • The most commonly observed adverse events were injection site reactions and flu-like symptoms.
  • Persistent elevations in liver transaminases (ALTs) above 3X ULN were observed in 8% of mipomersen-treated patients across all four studies.
  • Mipomersen-treated patients who were evaluated by MRI had moderate median increases in liver fat.
  • Genzyme expects to file for EU marketing approval of mipomersen for the treatment of patients with homozygous (Ho) FH and severe HeFH in the third quarter of 2011.
  • Genzyme also expects to file for US approval for the HoFH indication in the second half of 2011.

Statistics:

  • 71% and 62% of patients in the two trials had elevated Lp(a) levels ≥ 20 mg/dL at baseline.
  • 124 and 58 patients with HeFH were enrolled in the two trials, respectively.
  • 95% of patients with LDL-C levels ≥ 160 mg/dL had their levels reduced by 95% after receiving mipomersen.
  • 74% and 45% of patients had their LDL-C levels reduced by 74% and 45%, respectively, after receiving mipomersen.
  • 8% of mipomersen-treated patients had persistent elevations in ALTs above 3X ULN.

Sources:

  • Elisabeth Steinhagen-Thiessen, M.D., of the Lipid Ambulatory Clinic, University of Berlin, Germany, presentation at the 79th EAS Congress
  • Clinical Trials Week editors, article published on NewsRx.com
  • Genzyme press release
  • Isis Pharmaceuticals press release
  • European Atherosclerosis Society Congress program