Phase 3 trials of mipomersen for the treatment of hypercholesterolemia

Genzyme and Isis Pharmaceuticals announced results of two Phase 3 studies of patients who had high cholesterol levels while on maximally tolerated lipid-lowering therapy. The first study was a double-blind, placebo-controlled trial that included 58 patients with severe hypercholesterolemia who were already taking maximally tolerated lipid-lowering medications. Severe hypercholesterolemia patients were defined as those who have LDL-C levels ≥ 200 mg/dL with baseline cardiovascular disease (CVD) or LDL-C levels ≥ 300 mg/dL without CVD. Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo weekly for 26 weeks. In this study, mipomersen reduced LDL-C, the primary endpoint, by 36 percent compared with a 13 percent increase for placebo.

The second study was a double-blind, placebo-controlled trial that included 158 patients with hypercholesterolemia (LDL-C ≥ 100 mg/dL) and at high risk of developing coronary heart disease (CHD) who were taking a maximally tolerated dose of a statin. Patients were randomized 2:1 to receive a 200 mg dose of mipomersen or placebo weekly for 26 weeks. In this second study, mipomersen reduced LDL-C by 37 percent compared with a 5 percent reduction for placebo.

Mipomersen is a first-in-class apo-B synthesis inhibitor that reduces LDL-C by preventing the formation of atherogenic lipids. It acts by decreasing the production of apo-B, which provides the structural core for all atherogenic lipids, including LDL-C, which carry cholesterol through the bloodstream.

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