Oral ISIS 301012 yields encouraging Ph I data

USA-based Isis Pharmaceuticals says that a Phase I study of an oral formulation of its anticholesterol drug candidate, ISIS 301012, has demonstrated oral bioavailability and pharmacological activity.

The second-generation antisense drug targets apoB-100, a protein critical to the synthesis and transport of low-density lipoprotein cholesterol and very low-density lipoprotein, which are involved in heart disease. One month of dosing in healthy volunteers with an oral capsule formulation of the agent resulted in an average of 6% bioavailability and a statistically-significant average reduction of approximately 13% in apoB-100, and commensurate reductions in LDL-C as compared to placebo. The firm noted that lowering cholesterol levels is a key component in the prevention and management of cardiovascular disease.

In the trial, healthy volunteers received either oral ISIS 301012 or placebo over the study period. Treatment with the antisense drug adminstered with a penetration enhancer, resulted in a statistically-significant average reduction in apoB-100 of about 13% versus placebo (p=0.005). Reductions in LDL-C were also statistically-significant (p=0.001). Isis stressed that the the oral form of ISIS 301012 was generally well-tolerated.