Cadrenal Therapeutics, Inc. is set to initiate a Phase 3 clinical trial for its lead drug candidate, tecarfarin, a novel oral and reversible anticoagulant. The trial will evaluate tecarfarin's efficacy in preventing heart attacks, stroke, and death due to blood clots in patients with left ventricular assist devices (LVADs). This late-stage development aims to address the limitations of current anticoagulation therapies in patients with rare cardiovascular conditions.
Addressing Limitations of Current Anticoagulants
Currently, treatment guidelines advise the use of vitamin K antagonists (VKAs) like warfarin for patients with LVADs, end-stage kidney disease (ESKD) and atrial fibrillation (AFib), and mechanical heart valves. However, randomized controlled trials have not demonstrated clinical benefits with warfarin or direct-acting oral anticoagulants (DOACs) such as Eliquis and Xarelto in these populations. Tecarfarin, as a novel VKA, could potentially fill this therapeutic gap.
Metabolic Advantages of Tecarfarin
Warfarin, while used since the 1950s, is associated with adverse events, including bleeding, clotting, skin necrosis, and hair loss. It also has numerous drug-drug interactions due to its complex metabolic profile. Tecarfarin is designed to overcome these limitations by utilizing an alternative metabolic pathway (Carboxylesterase 2, CES2), which is abundant and less susceptible to saturation. Unlike warfarin, which is metabolized by multiple CYP450 isoenzymes and affected by genetic variants and enzyme inhibitors/inducers, tecarfarin's metabolism is less influenced by kidney function and drug interactions.
Phase 3 Trial Design and Regulatory Status
Cadrenal has designed a randomized, single-blind, multicenter Phase 3 study to compare tecarfarin with warfarin in LVAD patients. The final protocol will be announced following discussions with the FDA in Fall 2024. The FDA has granted Orphan Drug Designation (ODD) to tecarfarin for thrombosis prevention in LVAD patients, as well as ODD and Fast Track status for preventing systemic thromboembolism in cardiac patients with ESKD and AFib. ODD provides seven years of U.S. marketing exclusivity, while Fast Track status expedites the development and review process, potentially leading to priority review of the New Drug Application (NDA).
Market Potential and Valuation
Cadrenal estimates a U.S. patient population of approximately 15,000 individuals with LVADs, who are advised to be on continual anticoagulation therapy. If approved, tecarfarin could be utilized by the majority of these patients. The company projects peak sales of approximately $900 million seven years after a potential approval in 2028. For ESKD + AFib, Cadrenal estimates approximately 100,000 individuals in the U.S. with no current clinical evidence supporting any drug for thromboembolic event prevention. Positive Phase 3 results could lead to substantial market share, with projected peak sales of approximately $600 million.
