Isis Initiates Phase I Trial of Oral ISIS 301012 for Cardiovascular Disease

Isis Pharmaceuticals has initiated a Phase I study of an oral capsule formulation of ISIS 301012, a second-generation antisense inhibitor of apoB-100, for the lowering of high cholesterol.

The initiation of this trial expands the company's clinical development program for ISIS 301012. The subcutaneous form of the drug is completing a Phase I study and is expected to enter Phase II clinical trials later this year.

Data previously reported from the Phase I trial showed that subcutaneously administered ISIS 301012 produced rapid and prolonged reductions of its target, apoB-100, as well as low density lipid (LDL), very low density lipid and total cholesterol in healthy volunteers with elevated cholesterol. ApoB-100 is the sole lipoprotein of LDL cholesterol, the "bad" lipid involved in heart disease.

Goals of the oral formulation Phase I trial are to evaluate the oral bioavailability of ISIS 301012, and to demonstrate safety and the pharmacological effects of the drug in healthy volunteers. In the trial, volunteers will receive either oral ISIS 301012 or placebo over a one-month period. In animal studies, the oral formulation of ISIS 301012 reduced apoB-100, LDL cholesterol and total cholesterol.