Isis Pharmaceuticals, Inc. has started a phase II study evaluating ISIS-CRPRx in patients with paroxysmal atrial fibrillation. Atrial fibrillation (AF) involves an irregular and often rapid heart rate that commonly causes poor blood flow to the body.

Paroxysmal AF is a type of AF characterized by unpredictable episodes of AF that can occur as frequently as every day. Patients with AF can experience chest palpitations, chest pain, weakness and decreased blood pressure during an event. While the cause of paroxysmal AF is not known, elevated levels of CRP are associated with an increase in the severity of AF episodes. ISIS-CRPRx is being evaluated in patients with AF to measure the effect of lowering CRP on the frequency and duration of the episodes.

Richard Geary, senior vice president of development at Isis said, "CRP is elevated in many inflammatory disorders and can also be elevated in diseases with inflammatory components, like AF. Elevation of CRP in these diseases is usually associated with increased disease burden and worse disease outcome. In this study, we will evaluate the effect of selectively lowering CRP on the severity of AF in patients who are prone to frequent and unpredictable AF events. By selectively lowering CRP with ISIS-CRPRx, we hope to observe a decrease in the frequency and duration of AF events in these patients." "ISIS-CRPRx is the first drug to be evaluated in clinical studies that can selectively reduce CRP. In our phase I studies, we observed selective, dose-dependent reduction of CRP in healthy volunteers. Our phase II programme is designed to provide us with proof-of-concept data in diseases where elevated levels of CRP are predictive of severity of disease."

The phase II study is a randomized, placebo-controlled, multiple-dose study evaluating the safety and efficacy of ISIS-CRPRx as a single agent in approximately 20 patients with AF who have pacemakers. The study is designed to evaluate the effects of ISIS-CRPRx on the frequency and duration of AF episodes. In addition to studying ISIS-CRPRx in AF, Isis is also currently evaluating ISIS-CRPRx in a phase II study in patients with rheumatoid arthritis (RA), where CRP is chronically elevated. Top-line data from the phase II RA study is planned for the middle of this year.

"ISIS-CRPRx is the first drug to test the hypothesis that lowering CRP levels could produce therapeutic benefit to patients. Although we are currently only evaluating ISIS-CRPRx in patients with rheumatoid arthritis and AF, if we are successful in demonstrating a significant benefit to lowering CRP in one or both of these diseases, there is a significant potential for ISIS-CRPRx to have broad application in numerous diseases with large commercial opportunity," concluded Lynne Parshall, chief operating officer at Isis.

ISIS-CRPRx is an antisense drug that is designed to inhibit the production of C-reactive protein (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, RA 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 implicated 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.