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Study Presented at ACC Shows Treatment With ISIS 301012 Added to,Statins for Only 5 Weeks Results in 75% of Patients Achieving LDL-C,Levels Less Than 100 mg/dL and 50% of Patients Achieving LDL-C,Levels of Less Than 70 mg/dL

* ISIS 301012 coadministered with statins for only five weeks at 400 mg/week lowered LDL-C 47% beyond the levels achieved with statins alone, with similarly favorable effects on other atherogenic lipids

NEW ORLEANS and CARLSBAD, Calif., March 26, 2007 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. announced new results from its Phase 2 clinical trial of ISIS 301012 coadministered with statins presented today at the of Cardiology Annual Scientific Session (ACC) in New Orleans. In the study, patients with high cholesterol were treated for five weeks with up to 400 mg/week of ISIS 301012 added to ongoing stable doses of statins. Data from this study for dose cohorts through 300 mg/week were previously reported. In the 400 mg/week cohort, ISIS 301012 was well tolerated, and patients dosed per protocol experienced statistically significant median improvements in apoB-100, LDL-cholesterol (LDL-C), and triglycerides (TG) of 51%, 47%, 35%, respectively. Later this year, Isis plans to begin a longer-duration Phase 2 study of ISIS 301012 added to statins in patients with routine high cholesterol to define maintenance doses of ISIS 301012 which are expected to be in the range of 100-200 mg/week.

In this study, at a dose 400 mg/week four of eight patients achieved LDL-C levels below 70 mg/dL and six of eight achieved LDL-C levels below 100 mg/dL. Similarly at a dose of 300 mg/week, three of eight patients achieved LDL-C levels below 70 mg/dL and seven of eight patients achieved LDL-C levels below 100 mg/dL. For High-Risk patients, the recommended target levels of LDL-C are 100 mg/dL, and for Very High-Risk patients a target of less than 70 mg/dL should be seriously considered (see Adult Treatment Panel III Recommendations below). Patients in this cohort had baseline LDL-C levels ranging from 109 - 162 mg/dL and had been on statins for a median duration of four years. These results were achieved with only five
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