Isis Pharmaceuticals, Inc. has announced the final data from a clinical trial in which ISIS 301012 produced rapid, dose-dependent, and prolonged reductions of its target, ApoB-100, with concomitant reductions in low density lipoprotein (LDL or "bad" cholesterol), very low density lipoprotein (VLDL) and total cholesterol levels. These reductions occurred after only one month of dosing, and lasted more than 100 days. Lowering cholesterol levels is a key component in the management of coronary artery disease. ISIS 301012 selectively targets ApoB-100, the protein component of LDL cholesterol, according to a company release.
"ISIS 301012 is already showing the potential for an attractive profile, validating what we saw in pre-clinical studies, and we are excited about moving it forward in clinical development," said Mark Wedel, Isis' vice president of Clinical Research and CMO. "ApoB-100 has been of great interest in the cardiovascular community because of its critical role in cholesterol transport, and is a molecular target uniquely approachable with antisense technology. This unique means of lowering LDL cholesterol may enable more people than ever before to reach their recommended target levels of LDL with drug treatment," he added.
The goal of this placebo-controlled, dose-escalation Phase 1 study was to measure the safety and pharmacokinetic profile of ISIS 301012, and its ability to reduce several components of cholesterol important in the management of cardiovascular disease. The study enrolled 36 volunteers with elevated cholesterol, and tested ISIS 301012 doses of 50mg, 100mg, 200mg and 400mg. After an initial single dose for safety evaluation, subjects received a three dose loading regimen, followed by a once weekly subcutaneous dose for three weeks, the release added.