Isis Pharmaceuticals, Inc., a leading company in RNA-targeted drug discovery and development, has initiated a phase 2 study evaluating ISIS-FXIRx in patients with end-stage renal disease (ESRD) on hemodialysis.  In May 2015, Isis entered into an exclusive license agreement with Bayer HealthCare (Bayer) to develop and commercialize ISIS-FXIRx for the prevention of clotting disorders.

The phase 2 study is intended to further characterize the profile of ISIS-FXIRx and will provide essential data for Bayer's future clinical development programme for ISIS-FXIRx. Upon completion of the study and advancement of the programme by Bayer, Isis will be eligible to receive a $55 million payment.  

"ESRD patients receiving chronic dialysis are prone to increased thrombosis. However, antithrombotic treatment options for these patients remain limited because these patients also have a high risk of bleeding. ISIS-FXIRx is a first-in-class antisense drug in clinical development that has shown a significant reduction in clotting without increasing bleeding events in previous clinical studies. This phase 2 study furthers both our and Bayer's goal of initially providing ISIS-FXIRx to patients with high unmet need," said B. Lynne Parshall, chief operating officer at Isis Pharmaceuticals. "These data will support Bayer's plans for a robust development programme to optimize the clinical potential of this drug."

ISIS-FXIRx is designed to inhibit the production of Factor XI, a coagulation factor produced in the liver that is involved in the propagation of clots. The phase 2 study is a randomized, double-blind, placebo controlled study in which ISIS-FXIRx will be administered to approximately 50 patients with ESRD on hemodialysis. The first patient has already been dosed in this study that will evaluate the safety, pharmacokinetic and pharmacodynamic effects of weekly dosing of 200mg or 300mg ISIS-FXIRx for up to 12 weeks.

ISIS-FXIRx is an antisense drug in development for the prevention of clotting disorders. High levels of Factor XI increase the risk of thrombosis, a process involving aberrant blood clot formation that can be responsible for heart attacks and strokes, while Factor XI deficiency results in a lower incidence of thromboembolic events with minimal increase in bleeding risk. In a phase 2 comparator-controlled study evaluating the incidence of venous thromboembolic events, or VTEs, in patients treated with ISIS-FXIRx undergoing total knee replacement surgery, patients treated with 300mg of ISIS-FXIRx experienced a seven-fold lower rate of VTE as compared with those treated with enoxaparin (4.2% and 30.4%, respectively; p<0.001). In this study, ISIS-FXIRx was generally well tolerated with no observed differences in safety outcomes compared with enoxaparin. The data from this study was published in the New England Journal of Medicine in December 2014.

Isis and Bayer entered into an exclusive license agreement to develop and commercialize ISIS-FXIRx for the prevention of clotting disorders. After completion of ongoing activities at Isis, Bayer will assume all global clinical development as well as worldwide regulatory and commercialization responsibilities for ISIS-FXIRx. As part of the clinical development program, Bayer plans to evaluate the therapeutic profile of ISIS-FXIRx in patients for whom currently available anticoagulants may not be used, such as in patients with a high risk of bleeding due to multiple co-morbidities. Isis is eligible to receive milestone payments as the drug advances toward the market and is eligible to receive tiered royalties in the low to high twenty percent range on gross margins of ISIS-FXIRx.