Isis Reports That ISIS 301012 is Well Tolerated in Patients Treatedfor Five Or More Months- Twelve of Sixteen FH Patients in an Ongoing Open-Label Extension Study Have Been Dosed With ISIS 301012 for Approximately Five Months or More, and Four Have Been Dosed for More Than Six Months
CARLSBAD, Calif., October 05, 2007 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. announced the first safety results from its ongoing Phase 2 open-label extension (OLE) study of ISIS 301012 in patients with familial hypercholesterolemia (FH) on stable maximally tolerated lipid-lowering therapies. In addition, yesterday Isis announced results from a placebo-controlled Phase 2 study of ISIS 301012 in patients with heterozygous FH that were presented in a poster session today at the Drugs Affecting Lipid Metabolism (DALM) XVI International Symposium in New York City. Collectively, these results will be presented by Dr. John J.P. Kastelein in an oral session at DALM on Saturday at 3:45 p.m. E.T., and Isis will host a conference call Monday morning at 8:00 a.m. E.T. to discuss the results.
The ongoing Phase 2 OLE study includes 16 FH patients who had completed one of Isis' initial Phase 2 studies in FH patients and who subsequently enrolled in this open-label extension study. ISIS 301012 continues to be well tolerated by these patients with extended exposures and in the presence of continued maximally tolerated lipid-lowering therapies. As of September 17, four patients had received more than six months of weekly doses of ISIS 301012 over the course of both initial and OLE studies, and 12 of the 16 patients had total exposures of approximately five months or more. No new types of adverse events were observed with extended dosing or repeat exposures, no worsening of injection site reactions, and no increase in the frequency or severity of liver transaminase elevations.
John J.P. Kastelein, M.D., Ph.D., Chairman, Department of Vascular Medicine at the Academic Medical Center in Amsterdam, The Netherlands, also a principal investigator for the studies, commented, "We are particularly pleased to have had such an uneventful experience with patients in the long-term study. Until now, the longest exposures to ISIS 301012 had been three months, and now to have patients dosed for a total of more than six months without any tolerability issues is quite reassuring. Of course, we will all be eager to see more patients and longer exposure times to strengthen our confidence that ISIS 301012 could truly be a transformational new drug for the treatment of refractory high cholesterol."
About ISIS 301012 and Cholesterol
ISIS 301012 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. Cholesterol can be carried in the bloodstream in a variety of forms, with high-density lipoprotein, or HDL-C, being the good form, and low-density lipoproteins, or LDL-C, and very low-density lipoproteins, or VLDL-C, being bad forms directly involved in heart disease. Collectively, LDL-C, VLDL-C, and other bad forms of cholesterol are referred to as "non-HDL-C." The lowering of non-HDL-C is a key component in the prevention and management of cardiovascular disease. Isis plans to develop ISIS 301012 as the drug of choice for patients who are unable to achieve target cholesterol levels with statins alone or who are intolerant of statins. For future studies, including the registration studies for FH and the long-term coadministration study planned for patients with routine high cholesterol, both expected to begin this year, Isis has selected 200 mg/week as its development dose.
About Familial Hypercholesterolemia
Familial hypercholesterolemia is a genetic condition that results in markedly elevated LDL-C levels beginning at birth and heart attacks at an early age. People with the disease have consistently high levels of LDL-C, which leads to premature atherosclerosis of the coronary arteries. Current therapies for FH are inadequate, and the most severely affected patients may need apheresis, an expensive and time-consuming procedure that removes the "bad" cholesterol from the blood. Homozygous FH is rare, affecting about one in one million people, but heterozygous FH is much more common with a prevalence of approximately one in every 500 people.
Posted: October 2007