Isis Pharma Reports Positive Results From ISIS-APO(a)Rx Phase 1 Study

(RTTNews) - Isis Pharmaceuticals, Inc. (ISIS) announced positive results from a Phase 1 study with ISIS-APO(a)Rx. Isis plans to develop it to treat patients with high Lp(a) levels who are at high risk of experiencing cardiovascular events. The placebo-controlled, dose-escalation study was designed to assess the safety, tolerability and pharmacokinetics of ISIS-APO(a)Rx.

ISIS-APO(a)Rx is a wholly owned antisense drug targeting apolipoprotein(a) for the treatment of atherosclerosis. Apolipoprotein(a) contributes to the formation of plaque in arteries through its attachment to an LDL-C particle in a complex called Lp(a). High levels of Lp(a) are associated with an increased risk of atherosclerosis, coronary heart disease, heart attack and stroke. The company said, while statins and other lipid-lowering drugs have a modest effect on lowering Lp(a), patients with elevated Lp(a) are unable to reach recommended safe Lp(a) levels. ISIS-APO(a)Rx is designed to reduce Lp(a) by inhibiting the production of apolipoprotein(a).

ISIS-APO(a)Rx was evaluated in single and multiple doses ranging from 50 mg per week up to 400 mg per week for the single dose and 100 mg, 200 mg and 300 mg for the multiple dose. The company said, after only 3 weeks of dosing, subjects in the 100, 200 and 300 mg multiple-dose cohorts displayed a mean reduction of Lp(a) of 36, 62 and 82 percent, respectively, from baseline. The incoming range of Lp(a) in the study ranged from 10 mg/dL to 98 mg/dL. ISIS-APO(a)Rx reduction of Lp(a) was independent of the baseline Lp(a) measurement.

In addition to Lp(a) activity, subjects treated with 300 mg of ISIS-APO(a)Rx also experienced an up to 59 percent reduction in oxidized phospholipids, lipids that play an important role in proinflammatory and proatherogenic processes believed to be associated with Lp(a).

The company said, in the study, ISIS-APO(a)Rx demonstrated a good safety profile and was generally well tolerated.