Isis Pharmaceuticals Announces Initial Data from Phase 2 Clinical Trial of ISIS 301012

Strategic Insights -

Patients with high cholesterol receiving ISIS 301012, an antisense drug, achieved rapid and prolonged reductions in bad cholesterol, low density lipoprotein (LDL), and triglyceride levels. According to initial data from a phase 2 clinical trial, ISIS 301012 was well tolerated and showed significant reductions in apoB-100, LDL, total cholesterol, and triglyceride levels in patients with high cholesterol. The drug is being developed to treat patients with familial hypercholesterolemia (FH), a genetic disorder that causes extremely high cholesterol levels and results in the early onset of heart disease.

Key Takeaways:

  • ISIS 301012 produced rapid, dose-dependent and prolonged reductions in apoB-100, LDL, total cholesterol, and triglyceride levels in patients with high cholesterol.
  • At a dose of 200 mg/wk for 3 months, ISIS 301012 achieved a median percent reduction from baseline of 47% in apoB-100, 42% in LDL, 34% in total cholesterol, and 46% in triglycerides at day 99.
  • ISIS 301012 was well tolerated in the study, with no safety concerns or drug-drug interactions reported.
  • The drug has the potential to provide an accelerated pathway to commercialization due to the unmet medical need in patients with familial hypercholesterolemia.
  • The study is continuing to explore two higher doses (300 and 400 mg per week) of ISIS 301012.
  • Development plans for ISIS 301012 include rapidly developing the drug for patients with familial hypercholesterolemia and addressing the larger commercial market represented by patients with high cholesterol.
  • Isis is conducting phase 2 trials of ISIS 301012 in combination with statin therapy in patients with high cholesterol.
  • Isis is also conducting phase 2 studies of ISIS 301012 in FH and normal subjects.

Statistics:

  • Median percent reduction from baseline of 47% in apoB-100, 42% in LDL, 34% in total cholesterol, and 46% in triglycerides at day 99.
  • 30 patients with elevated cholesterol levels have been dosed over a period of 3 months with a dose of 50, 100, or 200 mg/wk of ISIS 301012.
  • Study parameters:

+ Total cholesterol: medians of 246-271 mg/dL for the four treatment groups.

+ LDL: medians of 154-173 mg/dL for the four treatment groups.

Sources:

  • Isis Pharmaceuticals, Inc. (ISIS)
  • Symphony GenIsis, Inc.
  • Symphony Capital Partners, L.P.
  • World Disease Weekly editors