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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

weeks of treatment with ISIS 301012.

The most common drug-related adverse events were painless mild to moderate injection site reactions. There was one possibly drug-related serious adverse event reported for the study: a patient in the 400 mg/dL cohort experienced fever more than 12 hours after receiving the first dose and subsequently dropped out of the study. This patient was not included in the per protocol analysis. In this high dose cohort, one patient had consecutive measurements of liver transaminases (ALT) above three times the upper limit of normal (3xULN); the maximal ALT observed in the study was 211 IU/L. Importantly, no patients evidenced liver chemistries that would suggest risk of liver injury (extremely high ALT or ALT elevations together with elevations in bilirubin greater than 2xULN). Patients in this study remain in follow-up.

According to John J.P. Kastelein, M.D., Ph.D., Chairman, Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands, lead investigator in the study, "ISIS 301012 continues to show exceptional promise as a new lipid-lowering agent. This study demonstrates that as an add-on therapy in patients on statins whose LDL-C levels are not adequately controlled, ISIS 301012 effectively enables patients to achieve target levels of LDL-C. This is an important clinical effect which, together its tolerability and lack of drug interactions, make ISIS 301012 an exciting drug for potential use in combination with other lipid-lowering therapies in the patients unable to derive sufficient benefit from available agents."

Mark Wedel, M.D., J.D., Isis' Chief Medical Officer, added, "ISIS 301012 is highly active and well tolerated in combination with statins, both in the routine high cholesterol population represented in this study, as well as in homozygous familial hypercholesterolemic patients on maximal concurrent lipid-lowering therapies. ISIS 301012 continues to perform to our highest ex
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