Date: 2014-12-07
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in The New English Journal of Medicine
Company: Isis Pharmaceuticals, now Ionis Pharmaceutitcals (USA - CA)
Product: ISIS-FXIRx, now IONIS-FXIRx
Action
mechanism: antisense oligonucleotide. ISIS-FXIRx is an antisense drug in development for the prevention of clotting disorders. It targets Factor XI, a clotting factor produced in the liver that is an important component of the coagulation pathway. 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 300 mg 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.
Disease: venous thrombolic events (VTE) in patients treated with ISIS-FXIRx undergoing total knee replacement surgery
Therapeutic area: Cardiovascular diseases
Country:
Trial
details: The Phase 2 study of ISIS-FXIRx in 293 patients undergoing TKA was a global, multi-center, open-label, comparator-controlled study comparing ISIS-FXIRx with enoxaparin. Patients in the ISIS-FXIRx-treated groups received either 200 mg or 300 mg of ISIS-FXIRx for six weeks prior to TKA surgery and six hours and three days after surgery. Patients in the enoxaparin group received 40 mg of enoxaparin the evening before surgery, and once daily thereafter for at least eight days. All patients underwent mandatory bilateral venography to detect deep vein thrombosis. Venograms and suspected bleeding events were evaluated by a blinded independent adjudication committee.
Latest
news: * On December 7, 2014, Isis Pharmaceuticals announced final data from its Phase 2 comparator-controlled study evaluating the incidence of venous thromboembolic events (VTE) in patients treated with ISIS-FXIRx undergoing total knee replacement surgery, or total knee arthroplasty (TKA). ISIS-FXIRx is designed to reduce the production of Factor XI, a coagulation factor that plays a key role in thrombosis. These data were published in The New England Journal of Medicine and will be presented at the 56th American Society of Hematology meeting as a late-breaking oral presentation on Tuesday, December 9, 2014. In the paper and presentation titled 'Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis' the authors report that ISIS-FXIRx-treated patients experienced a dose-dependent decrease in venous thromboembolic events. Patients treated with 300 mg 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). 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. Isis Pharmaceuticals is now planning to bring in a partner for later-stage development and commercialization of this program. * On May 22, 2014, Isis Pharmaceuticals announced positive top-line data from a Phase 2 comparator-controlled study evaluating the incidence of venous thrombolic events (VTE) in patients treated with ISIS-FXIRx undergoing total knee replacement surgery, or total knee arthroplasty (TKA). ISIS-FXIRx inhibits the production of Factor XI, a coagulation factor that plays a key role in thrombosis. In this study with a data cutoff of May 7, 2014, ISIS-FXIRx-treated patients experienced a dose-dependent decrease in VTEs. Patients treated with 300 mg of ISIS-FXIRx experienced a seven-fold (p<0.0001) lower incidence of VTEs compared to patients treated with enoxaparin. Patients treated with 200 mg of ISIS-FXIRx had comparable incidence of VTEs compared to patients treated with enoxaparin. Patients treated with ISIS-FXIRx and enoxaparin experienced a very low rate of bleeding with ISIS-FXIRx-treated patients experiencing numerically fewer bleeding events compared to patients treated with enoxaparin. Isis plans to report the full data at an upcoming scientific meeting. ISIS-FXIRx was well tolerated in the study. There were no observed differences in safety compared to the enoxaparin group. 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.
