We are focused on advancing the development of tecarfarin, a Phase 3-ready, anticoagulant designed using a retrometabolic drug design process which targets a different pathway than the most commonly prescribed drugs used in the treatment of thrombosis and AFib.
In March 2019, the FDA granted orphan drug designation, or ODD, for tecarfarin for the prevention of systemic thromboembolism of cardiac origin in patients with ESRD and AFib.
Tecarfarin has been evaluated in 11 human clinical trials in over 1,003 individuals. In Phase 1, Phase 2 and Phase 2/3 clinical trials, tecarfarin has generally been well-tolerated in both healthy adult patients and patients with ESRD and chronic kidney disease, or CKD.
Tecarfarin is Phase 3-ready with a positive safety profile.
We have established that tecarfarin has a similar MOA to that of warfarin and demonstrated that tecarfarin’s elimination from the body was not affected by severe kidney dysfunction.
Tecarfarin has been evaluated in 11 clinical trials in over 1,003 subjects: 269 patients were treated for at least 6 months and 129 patients were treated for one year or more.
In Phase 1, Phase 2, and Phase 2/3 clinical trials, tecarfarin has generally been well-tolerated in both healthy adult subjects and patients with ESRD.
In a Phase 2/3 randomized and blinded trial, 607 patients with indications for chronic anticoagulation were treated with either tecarfarin or warfarin. The Time in Therapeutic Range, or TTR, with tecarfarin was similar to that with well-managed warfarin and tecarfarin appeared to have a favorable safety profile and be well tolerated with only 1.6% of the blinded tecarfarin subjects suffering from major bleeding and no thrombotic events. When thrombotic and major bleeding events during the blinded period were combined, a numerical imbalance favoring tecarfarin over warfarin was seen (warfarin 11 subjects, 3.6 %; tecarfarin 5 subjects, 1.6 %).
In a subsequent Phase 1 study with 23 patients with chronic kidney disease, the metabolism of warfarin was inhibited, but not tecarfarin. The safety of repeated dosing of tecarfarin in CKD patients remained unknown. However, if the pharmacokinetic findings of this single-dose study are present with repeated dosing, tecarfarin may lead to dosing that is more predictable than warfarin in CKD patients who require anticoagulation therapy.
Pivotal Phase 3 Study
We are currently focused on advancing our pivotal Phase 3 trial, called the ACTOR AF Study, with an intent to initiate in the second half of 2023. It is expected to be a randomized, double-blind, placebo-controlled outcomes study of tecarfarin vs. placebo in 492 patients with both end-stage renal disease and atrial fibrillation who are not currently being treated with a chronic oral anticoagulant.
We have licensed out the rights to tecarfarin for several Asian markets including China, to Lee’s Pharmaceutical Holdings Limited, an integrated research-driven and market-oriented biopharmaceutical publicly listed company based in Hong Kong with over 25 years’ experience in the pharmaceutical industry in China. Lee’s Pharmaceutical Holdings Limited is developing tecarfarin as an anti-thrombotic for patients with mechanical heart valves. In 2020 and 2021, Lee’s Pharmaceutical Holdings Limited completed two Phase 1 studies in China and Hong Kong and is currently preparing for its Phase 2 trial, which is expected to begin patient enrollment in December 2022.