The Food and Drug Administration (FDA) has granted Fast Track designation to tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with end-stage renal disease (ESRD) and atrial fibrillation (AFib).

Tecarfarin is a novel oral vitamin K antagonist with a similar mechanism of action to warfarin, though it is metabolized differently. The Company believes that by avoiding cytochrome P450-mediated interactions, tecarfarin may potentially have an improved safety profile over warfarin.

The investigational treatment has been evaluated in 11 human clinical trials in over 1000 patients, including a phase 2/3 trial (EmbraceAC; ClinicalTrials.gov Identifier: NCT00691470), which included 607 patients with indications for chronic anticoagulation. Patients were randomly assigned to receive either tecarfarin or warfarin, with dose adjusted based on international normalized ratio (INR). Findings showed that the time in therapeutic range was similar between the tecarfarin and warfarin groups. Thrombotic and major bleeding events occurred in 11 patients treated with warfarin and 5 patients treated with tecarfarin.

Tecarfarin was also compared with warfarin in a phase 1 study that enrolled 23 patients with chronic kidney disease (CKD). Findings from this trial demonstrated that among CKD patients, the metabolism of warfarin was inhibited, while with tecarfarin, it was not.

The Company is expected to begin a randomized, double-blind, placebo-controlled phase 3 trial of tecarfarin (ACTOR-AF) in the second half of 2023. The study will include patients with both ESRD and AFib who are not currently on chronic oral anticoagulants.

“Patients with ESRD and AFib have not been well represented in clinical trials evaluating stroke prevention,” said Dr Sean Pokorney, an electrophysiologist, Assistant Professor of Medicine at Duke University, and Primary Investigator for the ACTOR-AF Tecarfarin versus placebo phase 3 Trial. “The development of tecarfarin is an exciting opportunity to collect randomized clinical trial data on stroke prevention in patients with ESRD and AFib, and tecarfarin provides a unique opportunity to optimize stroke prevention in patients with ESRD and AFib.”

The FDA’s Fast Track process allows for expedited review of drugs that are expected to fill an unmet need such as providing a therapy that may be better than currently available treatments.

References

  1. Cadrenal Therapeutics (Nasdaq: CVKD) granted FDA Fast Track designation for tecarfarin for prevention of systemic thromboembolism of cardiac origin in patients with end-stage renal disease and atrial fibrillation. News release. Cadrenal Therapeutics. Accessed January 23, 2023. https://www.prnewswire.com/news-releases/cadrenal-therapeutics-nasdaq-cvkd-granted-fda-fast-track-designation-for-tecarfarin-for-prevention-of-systemic-thromboembolism-of-cardiac-origin-in-patients-with-end-stage-renal-disease-and-atrial-fibrillation-301727778.html.
  2. Clinical trials: Advancing the development of tecarfarin for the treatment of ESRD + AFib. Cadrenal Therapeutics. Accessed January 23, 2022. https://www.cadrenal.com/clinical-trials/.