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Positive Phase 2 Data for ISIS-FXIRx for the Prevention of Venous Thrombosis in Patients Undergoing Total Knee Replacement Surgery Published in the New England Journal of Medicine

Data to be presented Tuesday, December 9 in the late-breaking session at the American Society of Hematology annual meeting

Thrombosis remains a leading cause of morbidity and mortality worldwide. Thrombosis is often treated with anticoagulants such as warfarin, oral Factor Xa and thrombin inhibitors. Although these treatments are effective, there are limitations that restrict or prevent their use in a number of indications. As such, there is a significant unmet need for safer and more effective anticoagulants.

ISIS-FXIRx is an antisense drug designed to reduce the production of Factor XI, a coagulation factor that plays a key role in propagation of clots, but not in the initiation of clots. Therefore, it is hypothesized that reducing Factor XI activity could decrease the number of clots without increasing bleeding risk. Indeed, human genetic studies show that humans with lower levels of Factor XI have decreased incidence of venous thrombosis whereas humans with elevated levels of Factor XI have a higher risk of thrombosis.

Isis conducted a Phase 2 study in patients undergoing total knee replacement surgery to compare the efficacy and safety of ISIS-FXIRx with enoxaparin. Results of this study were published online December 7, 2014 in the New England Journal of Medicine.

In this study, patients treated with 300 mg of ISIS-FXIRx experienced a seven-fold lower rate of venous thromboembolic events (VTE) as compared with those treated with enoxaparin (4.2% and 30.4%, respectively; p<0.001). Patients treated with 200 mg of ISIS-FXIRx had a rate of VTE comparable to that in patients treated with enoxaparin (26.9% and 30.4%, respectively). The rate of VTE in patients given enoxaparin is within the range documented in previous studies in this therapeutic setting. ISIS-FXIRx treatment was associated with a dose-dependent and sustained reduction in Factor XI activity that correlated with the lower rate of VTE. The rate of bleeding was low with ISIS-FXIRx and enoxaparin.

In this study, ISIS-FXIRx was well tolerated. There were no observed differences in safety outcomes compared with enoxaparin. In particular, there were no flu-like symptoms, and injection site reactions were infrequent and mild. There have been no drug-related serious adverse events reported to date.

The Phase 2 study was published ahead of print and on-line in the New England Journal of Medicine on Sunday, December 7, 2014.

Click here for more information

Click here to access the webcast slides

Click here to access Dr. Büller's slides

Reference:
Büller, H. et al. (2014) Factor XI Antisense Oligonucleotide for Prevention of venous Thrombosis. New England Journal of Medicine

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