Isis Pharmaceuticals trials C-reactive protein drug

Isis Pharmaceuticals, Inc. announced today it has initiated a Phase 1 study of ISIS 353512, an antisense drug that inhibits the production of C-reactive protein (CRP). CRP levels are frequently elevated in patients with a variety of diseases including cardiovascular disease, Crohn's disease, rheumatoid arthritis and end-stage renal disease.

The Phase 1 study of ISIS 353512 is a blinded, randomized, placebo-controlled, dose-escalation study designed to assess the safety and pharmacokinetic profile of ISIS 353512 as well as to assess the initial effects of the drug on baseline CRP levels in healthy volunteers. In addition, Isis is designing a broad Phase 2 program to investigate multiple indications for ISIS 353512.

"We believe that CRP plays an important causal role not only in cardiovascular disease but also in renal and inflammatory diseases. Based on our preclinical data, and the safety and pharmacological data we will obtain from this study, we plan to create a Phase 2 development plan that evaluates several of the most scientifically and commercially attractive indications for ISIS 353512," said Stanley Crooke, Chairman and Chief Executive Officer of Isis. "CRP is an excellent example of the power of our technology which enables us to efficiently develop drugs to any target and to select targets that provide the most significant therapeutic benefit in disease areas where new treatment options are desperately needed."

ISIS 353512 is an antisense drug that targets CRP. For many years, CRP has been used as a clinical biomarker of diseases with an inflammatory component, such as cardiovascular disease, Crohn's disease, rheumatoid arthritis and end-stage renal disease. Elevated levels of CRP have been linked to coronary artery disease and a growing body of evidence from clinical trials implicates CRP in cardiovascular disease progression. Although CRP's active participation in these diseases remains to be determined, several lines of evidence support a causal role of CRP in disease, suggesting that it may be therapeutically beneficial to decrease CRP levels in patients who are at risk for coronary events. In addition, elevated CRP levels have been associated with a worsening of overall outcome in conditions such as end-stage renal disease, suggesting that lowering CRP in these patients would be beneficial. In preclinical studies, ISIS 353512 produced dramatic suppression of liver and serum CRP levels.