Espero Biopharma late-clinical stage oral anti-coagulant candidate – Tecarfarin – addresses an unmet need – a solution with potentially fewer adverse and fatal drug reactions and the likelihood of improved stability in maintaining a therapeutic anti-coagulation level.
This drug product candidate may offer potential for treatment in patients with mechanical and prosthetic heart valves, as well as those with renal dysfunction. Tecarfarin is positioned to be a possible alternative to warfarin.
It may also present advantages over novel oral anti-coagulants that contain direct Thrombin inhibitors and Factor Xa inhibitors, because as a Vitamin K-Antagonist, Tecarfarin potentially maintains the ability to be counteracted in the event of an emergency.
See how Tecarfarin might compare to warfarin and Non-Monitoring Therapy (NMT).Read More
Monitoring & Maintaining the Established Therapeutic Range
Patients who require both short-term and long-term anti-coagulation are often monitored for their anti-coagulation status using the International Normalized Ratio (INR). The goal of any anti-coagulant is to stay within the established therapeutic range (2.0 to 3.0 for most conditions). Outside of the range, patients are at risk of bleeding or of forming blood clots.
Patients will typically submit blood work on a monthly basis to allow physicians to observe the INR. This is most often done through a lab, but some patients are utilizing an at-home testing process. Historically, warfarin presents challenges for maintaining a therapeutic INR, with patients reportedly in the ideal range only 50-58% of the time.
This is due to warfarin’s dependence on certain enzymes, its interactions with some foods and drug-to-drug interactions. Espero Biopharma’s drug candidate, Tecarfarin, has the potential to provide an alternative to warfarin that may offer greater stability for INR. It will likely still require monitoring, but patients on Tecarfarin during clinical trials registered in the target INR range a median of 71.5% of the time. Within the trial, the patient group’s experience with warfarin was a target INR a median 59.3% of the time.
Clinical trials are still underway and they continue to assess Tecarfarin’s potential for maintenance of the INR in the therapeutic range. Researchers are also studying Tecarfarin’s use in patients who are utilizing other drug therapies that have established problematic drug-drug interactions for warfarin, including fluconazole and amiodarone.
Many of the newest alternatives to warfarin – novel oral anti-coagulants (NOACs) – have shown unique risks for bleeding. These newer drugs utilize direct Thrombin inhibitors or Factor Xa inhibitors. Unfortunately, these drugs are challenged to utilize an antidote or reversal agent to restart clotting in the event of an emergency.
Tecarfarin, as a Vitamin K-Antagonist (VKA), could retain its antidote potential. This might add another level of safety for the patient. Clinical trials indicate that these antidotes have the potential to rapidly reverse the anticoagulation effect of Tecarfarin in the event of an emergency.
For Heart Valve Patients
Many patients who have undergone heart valve replacement also have indications for anti-coagulation. In the case of patients with prosthetic heart valves, the presence of a foreign material can stimulate a clotting response. Patients with mechanical heart valves (MHV) require chronic anti-coagulation.
Management of MHV patients can be challenging. To maintain an ideal INR, warfarin requires frequent dose adjustments. MHV patients tend to be younger – with nearly 40,000 MHV procedures performed annually primarily in patients 60 and younger. Tecarfarin may present an alternative for these patients. Clinical trials indicate that while Tecarfarin likely still requires monitoring, it may allow for more stable dosing because it could have fewer drug-drug interactions, food interactions and genetic variability.
Patients with bioprosthetic heart valves (BHV) do not necessarily require anti-coagulation. However, more than 25% of these patients eventually develop another heart condition, atrial fibrillation (AFib), which requires chronic anti-coagulation. The drug candidate, Tecarfarin, may be a suitable alternative for these patients as well, due to the known drug-drug interactions between warfarin and other AFib medications.
For Renal Dysfunction
Patients who require anti-coagulation therapy, while also dealing with renal dysfunction, can be especially challenging to treat. These patients may have issues with traditional Vitamin K-Antagonist therapy because of the tendency for medication to accumulate in the kidneys. Similarly, drug interactions with popular medications intended to treat renal insufficiency are common with current treatments.
As a drug candidate, Tecarfarin potentially offers an alternative. It is being developed to avoid dependency on a critical enzyme that may interfere with renal function. At the same time, the drug may avoid renal elimination and potentially avoid transport using the protein P-gp.
Learn more about Tecarfarin’s potential for renal patients.Read More