End-Stage Kidney Disease and Atrial Fibrillation
Patients with ESKD and AFib face a heightened risk of stroke and death, while their increased bleeding risk limits the safe use of standard anticoagulants. Safer, more predictable therapies are urgently needed.
Atrial fibrillation (AFib – a common heart rhythm disorder) increases the risk of serious adverse clinical outcomes, such as stroke and death, in large part because the rhythm disorder predisposes to clot formation in the heart, and the clots can dislodge, travel beyond the heart, and block blood flow to critical organs like the brain. AFib nearly doubles the anticipated mortality and increases the stroke risk by approximately fivefold in these patients. Chronic anticoagulant therapy is typically recommended to decrease this risk in AFib patients, but comes with its own risk of bleeding complications.
There are an estimated 816,000 Americans with end-stage kidney disease (ESKD – severe kidney disease), with approximately 70% on dialysis. Approximately 145,000 ESKD patients also have AFib. Patients with ESKD who also have atrial fibrillation have very high rates of stroke and death, but the use of anticoagulants in these patients becomes more difficult because of their even higher risk of bleeding.
The Problem
An Unmet Need with No Established Standard of Care
At present, there is no evidence to support the use of any drug for the prevention of thromboembolic events in patients with ESKD and AFib, in part due to their high risk of bleeding and the complexities of managing anticoagulants in patients who are on dialysis. With no approved treatment options for patients with ESKD and AFib there is no established standard of care for these patients.
Warfarin and the DOACS (direct-acting oral anticoagulants) are commonly prescribed medications for AFib patients, but not on dialysis. Most trials of anticoagulant therapy in atrial fibrillation have excluded dialysis patients due to their underlying high bleeding risk, the complexities of dialysis management, and because approved therapies for AFib have metabolic profiles that are potentially problematic in patients with severely compromised kidney function.
Our Solution
Tecarfarin: Designed to Improve Safety Without Compromising Effectiveness
Our lead drug candidate, tecarfarin, targets a different metabolic pathway than the most commonly prescribed drugs for the treatment of ESKD and AFib in order to potentially eliminate specific side effects while maintaining or improving effectiveness.
Tecarfarin has been evaluated in 11 human clinical trials in over 1,000 individuals. In Phase 1, Phase 2 and Phase 2/3 clinical trials that have been conducted thus far, tecarfarin has generally been well-tolerated in both healthy adult patients and patients with chronic kidney disease.
Tecarfarin is metabolized via a different metabolic pathway (the human carboxylesterase 2 pathway) than warfarin, thereby avoiding warfarin’s CYP450 metabolism in the liver. This HCES2 pathway is abundantly distributed throughout the body, unlike CYP450, which is confined to the liver. Although it exhibits genetic variability, the variants have not been shown to alter the clearance of the drug significantly.
Tecarfarin was granted an orphan drug designation (ODD) by the FDA for the prevention of systemic thromboembolism (blood clots) of cardiac origin in patients with ESKD and AFib. The FDA also designated the investigation of tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with ESKD and AFib as a Fast Track development program.
Prevalence
AFib is the most common arrhythmia, with its incidence and prevalence increasing over the last 20 years.
There are more than 809,000 Americans with ESKD, with approximately 70% on dialysis. Approximately 150,000 ESKD patients also have AFib.
AFib nearly doubles the anticipated mortality and increases the stroke risk by approximately five-fold in these patients.
