Bristol-Myers Squibb and Pfizer reported that an interim analysis of results from a Phase III study of apixaban for the prevention of venous thromboembolism (VTE) in patients undergoing knee replacement indicate that the primary endpoint of this study was not met.
   
The Phase III VTE prevention study known as ADVANCE-1 compared apixaban, an oral Factor Xa inhibitor given at a dose of 2.5 mg, twice daily, to the FDA-approved dose of Sanofi-Aventis’ enoxaparin, 30 mg given twice daily. The primary efficacy outcome was the total of symptomatic or asymptomatic deep vein thrombosis, pulmonary embolism, and death by any cause. The rate of the primary efficacy endpoint on apixaban was similar to enoxaparin (9.0% vs. 8.9%), but did not meet the pre-specified statistical criteria for non-inferiority compared to enoxaparin, which was expected to be 16%, based on previous trials.
   
The companies are considering further studies with different protocols in preventing VTE in knee surgery and will not submit the U.S. filing for VTE prevention in 2009 as planned. Programs directed towards VTE prevention including EMEA registrational studies, treatment of VTE, and the prevention of stroke in atrial fibrillation continue as planned.
   
Full results of the ADVANCE-1 trial will be presented in December. Also, new Phase II data of apixaban in acute coronary syndrome patients (ACS) will be presented at the upcoming meeting of the European Society of Cardiology (ESC).
   
“Bristol-Myers Squibb and Pfizer remain enthusiastic and committed to the clinical development program for apixaban,” said Jack Lawrence, vice president, R&D, Bristol-Myers Squibb. “[The companies] anticipate that the results of APPRAISE-1 being presented at ESC will provide important insight into the potential use of apixaban for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, which affects an estimated 2.7 million people around the world every year.”