Isis Pharmaceuticals cholesterol drug meets trial goals

In the trial, eight patients with routine high cholesterol on stable doses of less than or equal to 40mg/day of statins were treated with 200mg/week mipomersen for three months. Results were compared with those from 14 placebo-treated patients. All patients remained on stable statin therapy throughout the study.

Mipomersen treatment resulted in a 42% reduction in apoB and a 48% reduction in LDL-C, beyond reductions achieved with statin therapy alone. With five weeks of treatment at 200mg/week reductions in apoB and LDL-C were 24% and 30% respectively, so, as predicted, extending treatment with mipomersen from five weeks to 13 weeks led to further reductions in apoB and LDL-C.

Further, Isis reported results of an integrated safety analysis including data from more than 250 subjects treated with mipomersen in Phase I and Phase II studies. This analysis demonstrates that mipomersen has been well tolerated and that treatment with mipomersen did not result in evidence of liver toxicity. During the entire study periods, including dosing plus 90 day follow up, 5% and 7% of subjects treated with placebo or 200 mg/week of mipomersen, respectively, experienced ALT elevations of 150-250 IU/L.

Mipomersen is a second-generation antisense drug that reduces the production of apoB-100, a protein critical to the synthesis and transport of ‘bad’ cholesterol and a target that has proved to be undruggable using traditional, small-molecule approaches.

Jeffrey Jonas, executive vice president of Isis Pharmaceuticals, said: “Our clinical experience continues to demonstrate the lipid-lowering activity of mipomersen, which has been equally effective across multiple patient populations both as a single agent and in combination with lipid-lowering therapies. Furthermore, mipomersen’s lipid-lowering effects have been highly predictable. Based on this experience, we are very encouraged by mipomersen’s overall safety and efficacy profile.”