ARYx Therapeutics, Inc, a biopharmaceutical company, announced results from its phase-2/3 clinical trial, EmbraceAC, comparing its novel anticoagulant agent tecarfarin (previously ATI-5923) with the leading oral anticoagulant warfarin.
In this trial, tecarfarin demonstrated efficacy essentially the same as in earlier phase-2 studies but did not achieve the primary endpoint of superiority over warfarin, as measured by time in therapeutic range (TTR). This was due to the virtually unprecedented performance of warfarin in this trial. Using the International Normalized Ratio (INR), which is the standard measure of anticoagulation to evaluate TTR, the patients in the trial who were administered tecarfarin stayed within the target therapeutic range 74.0 per cent of the time treated as compared to those patients receiving warfarin who stayed within the target therapeutic range 73.2 per cent of the time (p=0.506). The result for the warfarin group was unexpected based upon the extensive history of prior studies and published literature for the drug. Tecarfarin appeared to be well tolerated by the patients in this pase 2/3 clinical trial.
"While we are obviously disappointed at the outcome of this trial, tecarfarin achieved the results we anticipated based upon two earlier phase-2 studies. We continue to demonstrate a time within therapeutic range of INR that remains consistent from trial to trial, whether dosing decisions are made by treating physicians or through a centralized dosing control. In contrast, warfarin patients did much better than we had reason to expect and as a result we did not achieve statistical significance. This appears to be due in no small part to the central dose control centre that we established for the trial, and to the ability of the centre to anticipate the potential daily pitfalls of warfarin use. Such oversight for warfarin control dosing was necessary for our double-blind trial even though it's not seen in normal clinical practice. An initial analysis of the data reinforces the importance of comparing normal tecarfarin administration to typical warfarin practice in a so-called real world setting," said Dr Paul Goddard, chairman and chief executive officer of ARYx. "There are still a lot of data to be analyzed from this trial. Once we have fully analyzed both the efficacy and safety results, we will continue our on-going partnership discussions with several large pharmaceutical companies to determine the best path forward in the future development of tecarfarin. Of course, as we have previously stated, we also remain focused on the licensing of budiodarone and ATI-7505."
Dr Linda Bavisotto, a board certified physician in Internal Medicine and Hematology, commented, "I've gained experience with tecarfarin therapy as an Investigator in an earlier study and as a member of the dose control center in the EmbraceAC study. Tecarfarin is relatively easy to administer since it appears to have less dose variability than warfarin, can achieve a time in therapeutic range not usually produced by warfarin in previous studies or in clinical practice, and may confer an advantage relative to warfarin of providing a larger range for titration of dose in situations where the therapeutic window may be tight. The improved performance of warfarin in the EmbraceAC study may be a consequence of the dose control centre clinicians' unified approach to dosing, including anticipatory dose adjustments and increased frequency of follow-up monitoring whenever known interactive concurrent medications were introduced by physicians at the study sites. While such proactively adjusted dosing might improve time in therapeutic range for warfarin in an ideally controlled trial, it does not diminish the apparent efficacy of tecarfarin."
Tecarfarin (previously ATI-5923) is modeled on the drug warfarin as an oral anticoagulation therapy for patients who are in danger of forming life-threatening blood clots as a result of atrial fibrillation, prosthetic heart valve replacement or venous thromboembolism.
ARYx Therapeutics is a biopharmaceutical company focused on developing a portfolio of internally discovered products designed to eliminate known safety issues associated with well-established, commercially successful drugs.