On 26 February, Isis Pharmaceuticals announced the initiation of a phase 2 study evaluating ISIS-CRP(Rx) in patients with paroxysmal atrial fibrillation. While the cause of paroxysmal atrial fibrillation is unknown, elevated levels of C-reative protein (CRP) are associated with an increase in the severity of atrial fibrillation episodes.
ISIS-CRP(Rx) is being evaluated in patients with atrial fibrillation to measure the effect of lowering C-reative protein on the frequency and duration of the episodes.
“C-reative protein is elevated in many inflammatory disorders and can also be elevated in diseases with inflammatory components, like atrial fibrillation. Elevation of C-reative protein 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 C-reative protein on the severity of atrial fibrillation in patients who are prone to frequent and unpredictable atrial fibrillation events. By selectively lowering C-reative protein with ISIS-CRP (Rx), we hope to observe a decrease in the frequency and duration of atrial fibrillation events in these patients,” said Richard Geary, senior vice president of development at Isis. “ISIS-CRP(Rx) is the first drug to be evaluated in clinical studies that can selectively reduce C-reative protein. In our phase 1 studies, we observed selective, dose-dependent reduction of C-reative protein in healthy volunteers. Our phase 2 programme is designed to provide us with proof-of-concept data in diseases where elevated levels of C-reative protein are predictive of severity of disease.”
The phase 2 study is a randomised, placebo-controlled, multiple-dose study evaluating the safety and efficacy of ISIS-CRP(Rx) as a single agent in approximately 20 patients with atrial fibrillation who have pacemakers. The study is designed to evaluate the effects of ISIS-CRP(Rx) on the frequency and duration of atrial fibrillation episodes. In addition to studying ISIS-CRP(Rx) in atrial fibrillation, Isis is also currently evaluating ISIS-CRP(Rx) in a phase 2 study in patients with rheumatoid arthritis, where C-reative protein is chronically elevated. Top-line data from the phase 2 rheumatoid arthritis study is planned for the middle of this year.
“ISIS-CRP(Rx) is the first drug to test the hypothesis that lowering C-reative protein levels could produce therapeutic benefit to patients. Although we are currently only evaluating ISIS-CRP(Rx) in patients with rheumatoid arthritis and atrial fibrillation, if we are successful in demonstrating a significant benefit to lowering C-reative protein in one or both of these diseases, there is a significant potential for ISIS-CRP(Rx) to have broad application in numerous diseases with large commercial opportunity,” concluded Lynne Parshall, chief operating officer at Isis.