MANAGING ANTICOAGULATION IN ACUTE AND SURGICAL CARE REMAINS COMPLEX
In acute care, where rapid response and reversibility are essential, clinicians need therapies that deliver stability without increasing bleeding risk. Current options offer neither the control nor the confidence required.
Oral VKAs and DOACs were designed and developed for long-term, chronic use – not necessarily for acute care settings, such as hospitals, or for surgery that requires procedural anticoagulation, like cardiac surgery. In those circumstances, where real-time monitoring and minute-to-minute adjustments may be necessary, oral therapy is not desirable, and intravenous options are much preferred. Moreover, in acute settings, it is also highly desirable to have reversal options if uncontrolled bleeding becomes a problem.
Unfractionated heparin (UFH) can be administered intravenously and rapidly adjusted, and its effects can be monitored with commonly available blood tests. It is reversible with protamine and remains the primary choice for anticoagulant therapy in acute settings; however, it is also associated with a significant risk of bleeding complications. A common side-effect is low platelet counts, which can occasionally be life-threatening and paradoxically present as clots. Heparin is also known to activate platelets, making them more prone to aggregate. For acute situations, it is administered by a continuous intravenous infusion and requires frequent monitoring with aPTT measurements and constant adjustment. Given the complexity of the coagulation cascade, different clinical circumstances require targeting different parts of the cascade, which may only be possible with high doses of heparin.
The Problem
Balancing Bleeding and Thrombosis in High-Stakes Procedures
Unfractionated heparin is not the perfect anticoagulant for all acute applications. There remains a strong desire for additional antithrombotic options for use in acute-care settings, such as complex cardiac surgery, where a narrow therapeutic range and a need for improved safety profile and reduced bleeding complications are present. While the current standard of care for cardiac surgery is heparin, the high doses of heparin used for cardiopulmonary bypass have their own substantial risk of bleeding complications, especially with re-do operations, in which there can be significant blood loss. An estimated 230,000 to 250,000 coronary artery bypass grafting cases occur globally each year.
Our Solution
Frunexian: Combining Potency, Predictability, and Procedural Control
Frunexian is a highly potent, fast-on/fast-off, selective small molecule that inhibits factor XIa activity in a reliable, dose-proportional fashion. Frunexian is a mechanism-based inhibitor that binds avidly and rapidly to Factor XIa, which can be an advantage for a target like Factor XIa that requires a high degree of target engagement for efficacy. Those pharmacokinetic characteristics, along with limited dependence on renal clearance mechanisms, make frunexian well-suited for use in a critical care environment.
Unlike other IV small molecules under development, frunexian is the only one specifically targeting the acute/critical care hospital setting. All other agents, whether small molecules or antibodies, are targeting chronic indications.