Bristol-Myers Squibb and Pfizer has presented some fairly promising mid-stage data for their investigational oral anticoagulant apixaban in patients with acute coronary syndrome, a week after a study in another indication for the drug failed.
Results from a 1,715-patient Phase II trial called Appraise-1 were presented at the European Society of Cardiology meeting in Munich, which compared the current standard of care for ACS, including aspirin and Sanofi-Aventis/B-MS’ Plavix (clopidogrel) with apixaban on top of the standard of care.
The data revealed that apixiban appeared to reduce the relative risk of cardiovascular death, non-fatal heart attack, severe recurrent ischaemia and non-haemorrhagic stroke by 27% when taken at the lowest dose (2.5mg) twice daily and by 39% when patients took 10mg of apixaban once daily. However B-MS and Pfizer noted that the six-month study was not powered to demonstrate statistical signifance of the findings.
On a less positive note, the data also revealed that the incidence of major bleeding plus clinically relevant non-major bleeding was 5.7% for patients who received 2.5mg twice a day, 7.9% for those on the higher dose, and 3% for those given standard care alone.
“One of the most vexing problems in cardiology is identifying the right combination of drugs that can inhibit clot formation but not increase the risk of serious bleeding,” said study lead John Alexander of Duke University Medical Center, who presented the findings in Munich. He noted that two arms of the study were discontinued because patients were experiencing unacceptable rates of bleeding but said the data shows that adding 5mg or 10mg of apixaban to a regimen of aspirin or aspirin and clopidogrel “in patients hoping to prevent a second heart attack may offer therapeutic potential.” However, “this needs to be definitively demonstrated in a statistically significant manner in large, well-controlled studies,” Dr Alexander concluded.
The details of Appraise-1 were eagerly anticipated, coming as they did just a week after B-MS and Pfizer said that they will not be seeking approval for apixaban, a novel, oral Factor Xa inhibitor, in 2009. That decision was based on an early evaluation of results from a Phase III study, Advance-1, for the prevention of venous thromboembolism in patients undergoing total knee replacement which indicated that the primary endpoint was not met, ie non-inferiority to Sanofi’s Lovenox (enoxaparin).
The ACS data looks much better but apixaban has still got some ground to make up on Bayer/Johnson & Johnson’s Xarelto (rivaroxaban), another Factor Xa inhibitor, which was recently recommended for approval by the European Committee for Medicinal Products for Human Use for the prevention of VTE in patients undergoing elective hip or knee replacement surgery. Boehringer Ingelheim’s Pradaxa (dabigatran etexilate), an oral direct thrombin inhibitor, has already been approved in the latter indication.
