Isis Pharmaceuticals, Inc, a leader in RNA-targeted technology, with a pipeline of 38 drugs to treat various diseases, has entered into an exclusive license agreement with Bayer HealthCare (Bayer), a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials, to develop and commercialise ISIS-FXIRx for the prevention of thrombosis.
Under the terms of the agreement, Isis is eligible to receive up to USD 155 million in near-term payments, including an immediate USD 100 million up-front payment and a USD 55 million payment upon advancement of the programme 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 per cent 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 commercialisation responsibilities for ISIS-FXIRx.
As part of the clinical development programme, 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.
"We believe Bayer, a leading pharmaceutical company in the treatment of thrombotic disease, is the ideal partner for ISIS-FXIRx. This transaction further demonstrates Bayer's commitment to the field. Bayer has the expertise, commitment and resources to develop ISIS-FXIRx in areas where unmet medical needs exist. We are pleased with the value of this partnership, which supports a robust development programme to maximize the value of ISIS-FXIRx globally and which allows us to participate significantly in future commercial success," said Stanley Crooke, PhD, MD, chief executive officer at Isis Pharmaceuticals.
"We believe that this transaction represents the right deal, with the right partner and the right development plan."
"This first-in-class FXI inhibitor perfectly complements our in-house thrombosis pipeline and is an innovative development candidate for a variety of anti-coagulation needs," said Dr Joerg Moeller, member of the Bayer HealthCare Executive Committee and head of Global Development.
"We believe the novel mechanism of Factor XI inhibition may offer an additional pathway for treating patients for whom there are currently no suitable therapeutic options available. We share a common vision with Isis in developing ISIS-FXIRx to its full potential."
This transaction is subject to clearances under the Hart-Scott Rodino Antitrust Improvements Act.
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 per cent and 30.4 per cent, 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.