Bayer announced the start of a Phase III clinical development program OCEANIC to investigate the efficacy and safety of asundexian, an oral Factor XIa (FXIa) inhibitor, as a potential new treatment in patients with atrial fibrillation and in patients with a non-cardioembolic ischemic stroke or high-risk transient ischemic attack.
Factor XI is a protein in the blood which is converted into its active enzyme form (Factor XIa) as part of the blood coagulation cascade. Factor XI is a promising and differentiated target for the development of safer anticoagulants because of its critical role in pathological versus normal thrombus formation uncoupling hemostasis from thrombosis. Patients with congenital Factor XI genetic deficiency demonstrate a lower risk for venous thromboembolism and ischemic stroke but rarely have spontaneous bleeding.1 The OCEANIC program is designed to assess the potential of asundexian to protect patients from pathological thrombus formation without a corresponding increase in bleeding risk aiming to improve the benefit-risk profile compared to current treatment options. FXIa inhibitors that selectively modulate coagulation through FXIa inhibition could represent a fundamentally new approach to antithrombotic treatment, as they prevent thrombosis yet still allow haemostatic clots that are crucial to repair injury.
The initiation of the OCEANIC program is based on the data from the Phase II PACIFIC program. The PACIFIC-STROKE2 and PACIFIC-AMI3 Phase IIb trials compared the safety and efficacy of asundexian with placebo in patients following acute non-cardioembolic ischemic stroke or acute myocardial infarction (AMI), respectively. Both trials showed consistent safety results for asundexian comparable to placebo arm, regardless of background therapy. The data from the completed PACIFIC Phase IIb clinical trial program, including previously published data from the PACIFIC-AF4 (atrial fibrillation) study, further support the hypothesis that asundexian may reduce the risk of thrombotic events without significantly impacting the risk of bleeding.
“Concerns regarding bleeding risk result in the fact that, currently, many patients are treated sub-optimally or not at all”, said Dr. Ashkan Shoamanesh, Associate Professor of Medicine (Neurology) at McMaster University. “In the PACIFIC trials, we saw encouraging bleeding data, suggesting that asundexian may prevent thromboembolic events without a corresponding increase in bleeding risk. If confirmed, asundexian could offer a potential new therapy and help improve patient care.”
“We have had significant advances for our patients requiring anticoagulation with the introduction of the direct oral anticoagulants. But we still have patients who do not get the therapy, or for whom there is a need for alternative treatment options in thrombosis prevention,” said Manesh Patel, Richard S. Stack Distinguished Professor, Chief of the Division of Cardiology and Co-Director of the Heart Center at Duke University. “The Phase III OCEANIC program is the essential next step to generate more data for asundexian as a potential new treatment option for this large disease area.”
“With deep experience and disease understanding, Bayer is particularly strong in the field of anticoagulation and has made significant contributions to the lives of over 100 million patients. Focusing on Factor XIa inhibition, we are striving for another paradigm shift to investigate a new class of antithrombotics with the potential of an improved benefit-risk profile compared to current treatment options,” said Christian Rommel, Member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Research and Development. “The underlying science of FXIa and the phase II data especially supporting the safety of asundexian make us confident to move the investigational compound forward into Phase III addressing significant therapeutic areas. OCEANIC is one of the largest Phase III endeavours Bayer has undertaken so far. Our clear goal is to develop a new treatment option to prevent thrombotic events.”
The OCEANIC Phase III clinical development program will start with two large multinational studies, OCEANIC-AF and OCEANIC-STROKE, expected to enroll up to 30,000 patients in over 40 countries.
OCEANIC-AF will test asundexian against apixaban in patients with atrial fibrillation. The primary objective of OCEANIC-AF is to determine the effects on prevention of stroke and systemic embolism and, in addition, to show a lower risk for bleeding in patients receiving asundexian when compared to patients receiving apixaban. The first patients are expected to be enrolled later this year.
OCEANIC-STROKE will be a placebo-controlled study on top of standard of care antiplatelet therapy in patients after a non-cardioembolic ischemic stroke or high-risk ischemic attack. The primary objective of the Phase III study OCEANIC-STROKE is to show a lower risk for ischemic stroke in comparison to placebo, without a significant increase in bleeding risk. By selectively modulating coagulation, the once-daily oral FXIa inhibitor asundexian is being investigated as a potential new treatment option in thrombosis prevention.
