Pfizer and Bristol-Myers Squibb's apixaban has suffered a setback in trials against venous thromboembolism (VTE).

An early evaluation of results from a phase III study investigating the prevention of VTE in patients undergoing knee replacement surgery indicates that the primary endpoint was not met.

The indication is the most advanced of two that the companies are pursuing for apixaban, and the disappointing results will delay its US filing for approval until at least 2010.

But BMS's vice president for research and development Jack Lawrence insisted: "BMS and Pfizer remain enthusiastic and committed to the clinical development programme for apixaban."

The study, ADVANCE-1, failed to show that apixaban, given at a dose of 2.5-mg twice daily, was more effective than the FDA-approved dose of enoxaparin: 30-mg twice daily.

The drug is a novel, oral Factor Xa inhibitor with potential to prevent and treat blood clots in the veins and arteries and the companies say they are considering further clinical work with different protocols in preventing VTE in knee surgery.

Studies in the drug's second potential indication - the prevention of stroke in atrial fibrillation will continue as planned, as will plans for a European licence in VTE.

The manufacturers are also pinning some hope on new Phase II data in acute coronary syndrome patients (ACS) ¿ that is, those who suffer heart attacks or severe chest pain - which was presented this week at the meeting of the European Society of Cardiology (ESC) in Munich.

The APPRAISE-1 study compared the current standard of care for ACS, including aspirin and clopidogrel, and apixaban came out on top.

John H Alexander, the study's principal investigator at the Duke Clinical Research Institute in North Carolina, said the data suggested that anticoagulation with apixaban on top of current standards of care and continued beyond the initial hospitalisation period may reduce the risk of a second heart attack, stroke or death.

"As with all effective anticoagulants, there was a trade off with some increase in bleeding for reduction in risk," he warned.

ACS affects an estimated 2.7 million people worldwide every year. Lawrence said the study would help to identify appropriate apixaban dosing for future studies, thus balancing efficacy benefit while minimising bleeding for ACS patients.

"The objective is to identify whether apixaban can reduce the risk of secondary cardiovascular events, offering significant improvements for patient lives, as well as reducing the economic burden of cardiovascular disease around the world," he added.

pharmafocus@wiley.com