Bristol-Myers Squibb Company and Pfizer Inc provided an update on the apixaban clinical development program. The companies announced that new Phase II data in acute coronary syndrome patients (ACS) will be presented at the upcoming meeting of the European Society of Cardiology (ESC).

In addition, Bristol-Myers Squibb and Pfizer reported that an early evaluation of results from a Phase III study of apixaban for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement indicates that the primary endpoint of this study was not met.

The Phase III VTE prevention study known as ADVANCE-1 compared apixaban, a novel, oral Factor Xa inhibitor given at a dose of 2.5 mg, twice daily, to the FDA-approved dose of enoxaparin, 30 mg given twice daily. The primary efficacy outcome was a composite of symptomatic or asymptomatic deep vein thrombosis, pulmonary embolism, and death by any cause. The rate of the primary efficacy endpoint on apixaban was numerically similar to that observed with enoxaparin (9.0% vs. 8.9%, p=.064), but did not meet the pre-specified statistical criteria for non-inferiority compared to enoxaparin. The actual enoxaparin VTE rate of 8.9 percent was lower than the expected VTE rate of 16 percent seen in previous similar clinical trials, resulting in an inability to demonstrate non-inferiority.

In ADVANCE-1, there were no unexpected findings in adverse events for apixaban compared to enoxaparin. The major bleeding event rate for apixaban was numerically lower, but was not significantly lower, than enoxaparin (0.7% vs. 1.4%, p=.053). The composite rate of clinically relevant non-major bleeding and major bleeding was significantly less in patients who received apixaban than those who received enoxaparin (2.9% vs. 4.3%, p =.034).

Full results of the ADVANCE-1 trial have been submitted to the American Society of Hematology Meeting (ASH) for presentation in December.