Isis Pharmaceuticals, Inc. is initiating a Phase 2 clinical trial of its drug ISIS-FXIRx used to inhibit clotting in patients undergoing total knee arthroplasty (TKA). According to the drugs proponents, it inhibits the production of Factor XI, a coagulation factor produced in the liver that is involved in the formation of clots. In this study, Isis will evaluate the effectiveness of ISIS-FXIRx in reducing the number of thrombotic events in patients after TKAs without increasing bleeding.
“Although there are a number of anti-coagulants on the market today that are considered standard-of-care in multiple therapeutic settings, complications of bleeding associated with these medications remain high and can lead to fatal outcomes, ” said Harry Buller, Ph.D., M.D., professor of medicine at Academic Medical Center in The Netherlands. “Factor XI plays a key role in the formation of clots but inhibiting it does not cause bleeding. Humans who are deficient in Factor XI tend to have a lower incidence of stroke and venous thrombosis with no evidence of spontaneous bleeding episodes.”
The Phase 2 study is a global, multi-center, open-label, comparator-controlled study in up to 400 patients who are undergoing TKAs. The study will compare ISIS-FXIRx safety and activity to enoxaparin, a commonly used anti-coagulant. In a Phase 1 study in healthy volunteers, ISIS-FXIRx produced robust dose-dependent, statistically significant reduction of greater than 80% in Factor XI activity with no bleeding events observed, according to a company report.
Given the mechanism of Factor XI inhibition, Isis officials believe that the drug could be used broadly to prevent deep vein thrombosis or pulmonary embolism in many different therapeutic settings, including stroke, myocardial infarction and with surgeries such as knee or hip replacement, where additional safe and effective anti-thrombotic drugs are needed. Isis Pharmaceuticals was founded in 1989 and is located in Carlsbad, California.
