The final data from the phase I trial showed the drug candidate ISIS 301012 to be capable of producing rapid 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. ApoB-100 levels were reduced on average by 30%-52% and LDL from 17%-48%.
The goal of the 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 at four different dose strengths.
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 minimum active dose in the study was 50mg per week. No treatment-related serious adverse events were reported at any dose level.
ISIS 301012 selectively targets ApoB-100, the protein component of LDL cholesterol. It is this component that has been implicated in the transport of cholesterol and is therefore implicated in cardiovascular disease.
Additional phase II trials will commence in the second-half of 2005 to explore ISIS 301012 as a monotherapy to optimize dose and schedule, as a combination to statins. An oral formulation of ISIS 301012 is currently in phase I studies.