Tecarfarin, an oral anti-coagulant drug candidate, represents Espero Biopharma’s core development program. Tecarfarin has completed a Phase 2 clinical trial to assess its safety and efficacy. The trial was also designed for comparator research to warfarin.
Safety & Tolerability
The results of the first Phase 2 trial showed a potential initial acceptable safety and tolerability profile for Tecarfarin. The drug candidate also demonstrated its efficacy and ability to maintain a patient’s anti-coagulation status – as measured by the International Normalized Ratio (INR) – to within a target therapeutic range. The trial population focused on patients who had a history of difficult INR control utilizing warfarin, defined as maintaining within the target INR less than 45% of the time.
This indicator is critical to the overall effectiveness of an anti-coagulant. Research shows that for every 10% increase in a patient’s time out of the INR range, the risk of mortality due to significant thrombotic or hemorrhagic events increases by 29%.
This trial was designed to establish the optimal dosing regimen and INR monitoring schedule. The 12-week trial assisted researchers in determining the time to reach stable dosing, defined as three consecutive INR readings in the therapeutic range without adjustment. This trial, involving 66 patients, resulted in achieving the target INR rage 71.5% of the time after a three-week dose tritation. The historical experience of this same group of patients on warfarin achieved the INR target a median 59.3% of the time.
Phase 1 Clinical Trials
Espero Biopharma completed five Phase 1 clinical trials in 156 healthy volunteers. The trials indicated no unexpected safety signals, including adverse events, vital signs, ECG, and laboratory testing. There have been no frequent or consistent adverse events suggestive of off-target toxicity. Within the trials, mild side effects typical of an anti-coagulant were experienced, including headache and gastrointestinal effects. Adverse events were mild, including bruising and nose bleeds.
These clinical trials also demonstrated Tecarfarin’s probable ability to be reversed with Vitamin K or fresh plasma, as expected of a Vitamin K-Antagonist (VKA).
Phase 1 clinical trials also studied the impact of this potential drug on other medications, such as Fluxonazole, and found no affect on blood levels. A similar drug interaction study for Amiodarone is currently underway.
In vivo research indicated that drug candidate, Tecarfarin, could be associated with selective reductions in VKOR-dependent coagulation factors (II, VII, IX and X). VKOR-independent factors have the potential to be unaffected. These studies also indicated that anti-coagulation was unaffected by treatment with CYP450 inhibitors. Also, well-known teratogenic effects of warfarin were not seen in reproductive toxicity studies.