Date: 2016-11-01
Type of information: Milestone
Compound: IONIS-FXIRx
Company: Bayer Healthcare (Germany) Ionis Pharmaceuticals (USA - CA)
Therapeutic area: Cardiovascular diseases
Type agreement: licensing
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: prevention of thrombosis
Details: * On May 4, 2015, Isis Pharmaceuticals has entered into an exclusive license agreement with Bayer HealthCare (Bayer) to develop and commercialize ISIS-FXIRx for the prevention of thrombosis. 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. This transaction is subject to clearances under the Hart-Scott Rodino Antitrust Improvements Act.
Financial terms: Under the terms of the agreement, Isis is eligible to receive up to $155 million in near-term payments, including an immediate $100 million up-front payment and a $55 million payment upon advancement of the program following a Phase 2 study in patients with compromised kidney function. Isis is also eligible to receive milestone payments as the drug advances toward the market. In addition, Isis is eligible to receive tiered royalties in the low to high twenty percent range on gross margins of ISIS-FXIRx.
Latest news: * On November. 1, 2016, Ionis Pharmaceuticals announced positive data from a phase 2 placebo-controlled study evaluating IONIS-FXIRx in patients with end-stage renal disease (ESRD) on hemodialysis. In this Phase 2 study patients treated with IONIS-FXIRx achieved statistically significant, dose-dependent reductions in Factor XI activity. Upon review of the Phase 2 data and potential advancement of the program by Bayer, Ionis will be eligible to receive a $55 million payment. * On June 5, 2015, Isis Pharmaceuticals announced that its license agreement with Bayer HealthCare (Bayer) to develop and commercialize ISIS-FXIRx has received clearance under the Hart-Scott-Rodino Antitrust Improvements Act. Based on this approval, Bayer will pay Isis an immediate $100 million up-front payment. In total, Isis is eligible to receive up to $375 million in payments, including the upfront payment and a $55 million near-term milestone payment upon advancement of the program following the Phase 2 study in patients with compromised kidney function. In addition, Isis is eligible to receive tiered royalties in the low to high twenty percent range on gross margins of ISIS-FXIRx. 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.
