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Isis Pharmaceuticals Reports Positive Phase 2 Data for ISIS 301012,in Familial Hypercholesterolemia Patients Presented at ACC

* Homozygous FH patients already being treated with maximally tolerated lipid-lowering therapies experienced 50% further reductions in LDL-C with similar reductions in other atherogenic when treated with 300 mg/week ISIS 301012

NEW ORLEANS, and CARLSBAD, Calif., March 26, 2007 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. announced results from its ongoing Phase 2 clinical trial of ISIS 301012 in patients with homozygous familial hypercholesterolemia (HoFH), presented today at the of Cardiology Annual Scientific Session (ACC) in New Orleans. Data were presented for three HoFH patients on concurrent high-dose lipid-lowering therapies. Two patients had completed at least eleven weeks of dosing at 300 mg/week of ISIS 301012 added to ongoing lipid-lowering therapies and experienced at least 50% further reductions in LDL-cholesterol (LDL-C), with similar effects on apoB and other apoB-containing lipoproteins and triglycerides (TG). A third patient had apoB and LDL-C reductions of 29% and 32%, respectively, after just six weeks of dosing. HDL-cholesterol (HDL-C) remained stable or increased slightly in these patients. ISIS 301012 was well tolerated in the study. ISIS 301012 has been granted orphan drug status for the treatment of homozygous FH and Isis plans to begin registration-directed studies for FH in 2007.

According to Evan Stein, M.D., Ph.D., Director, Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio, lead investigator in the study, "I can't overemphasize the importance of these results. ISIS 301012 produced much more dramatic lipid-lowering effects in these patients than we have ever seen with any other therapeutic agent, including statins and MTP inhibitors. That it did so in patients who were already on maximal lipid-lowering therapies, and did so with such excellent tolerability, is truly remarkable. Achieving an LDL-C less than 100 mg/dL in a homozygous FH patient, other than
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