Cadrenal Therapeutics is advancing the development of tecarfarin, a novel vitamin K antagonist (VKA), as a safer and more effective anticoagulant option for patients with implanted cardiac devices, particularly those with left ventricular assist devices (LVADs). Recent data and a proposed clinical trial protocol were presented at the European Association for Cardio-thoracic Surgery (EACTS) Mechanical Circulatory Support Summit in Prague, Czech Republic.
The presentation, titled Tec arfarin and H emocompatibility with LVAD Therapy (TECH-LVAD), highlighted tecarfarin's potential to improve the Time in Therapeutic Range (TTR) and reduce bleeding events in patients with the Abbott HeartMate3 (HM3) LVAD. Dr. Mandeep R. Mehra, from Brigham and Women's Hospital and Harvard University, presented the data and outlined the proposed trial design.
Rationale for Tecarfarin in LVAD Patients
Patients with LVADs require chronic anticoagulation to prevent thromboembolic events. Warfarin, a commonly used VKA, is associated with significant adverse events, including bleeding, due to its narrow therapeutic window and interactions with other drugs and food. Direct oral anticoagulants (DOACs) are not recommended in this population, leaving an unmet need for safer anticoagulation options.
Dr. Mehra emphasized the inverse relationship between bleeding rates and TTR in HM3 patients. Data from previous trials suggest that tecarfarin has the potential to improve TTR compared to warfarin. Notably, a trial in end-stage kidney disease (ESKD) patients showed that tecarfarin exposure is not altered by ESKD, while warfarin exposure is increased. This is a critical differentiator, as many LVAD patients have kidney impairment.
Proposed TECH-LVAD Trial
The TECH-LVAD trial, recently submitted to the FDA, aims to compare tecarfarin to warfarin in HM3 LVAD patients. The primary endpoint is the reduction of bleeding events. The trial is designed to address the need for a VKA option that can reduce the bleeding complications associated with HM3 use in advanced heart failure.
"In the proposed TECH-LVAD trial, we plan to study a much-needed VKA option with the expectation of reducing bleeding events that accompany use of the HM3 LVAD in advanced heart failure. Tecarfarin could potentially be an important therapy for patients with LVADs who all require chronic anticoagulation," said Dr. Mehra.
Cadrenal's Perspective
Cadrenal Therapeutics is actively engaged in discussions with the FDA and Abbott regarding the tecarfarin study in LVAD patients. The company aims to increase the visibility of tecarfarin data to accelerate its development and prepare for investigator outreach and patient recruitment for the trial.
Tecarfarin has received orphan drug designation for advanced heart failure patients with implanted LVADs, as well as orphan drug and fast-track status for end-stage kidney disease patients with atrial fibrillation. Cadrenal is also planning to study tecarfarin in patients with mechanical heart valves experiencing anticoagulation difficulties.
