Dose-Ranging Study Examined Apixaban in Patients Taking Commonly Used Anti-Platelet Therapies

Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc (NYSE: PFE) announced today the results of a Phase 2 dose-ranging study (APPRAISE-1) involving the investigational compound apixaban in patients with acute coronary syndrome (ACS, commonly known as heart attack or severe chest pain). The study compared the current standard of care for ACS, including aspirin and clopidogrel, with apixaban on top of the standard of care. The study results were presented during a late-breaking session at the annual European Society of Cardiology (ESC) meeting in Munich, Germany.

Apixaban, which is currently being developed by the two companies, is an investigational oral, highly selective factor Xa inhibitor, a new class of agents with therapeutic potential to prevent and treat blood clots in the veins and arteries.

“The APPRAISE-1 study provided encouraging trends suggesting that anticoagulation with apixaban on top of current standards of care and continued beyond the initial hospitalization 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. We look forward to further studies of apixaban in patients with ACS to fully understand its potential beyond current therapies in this population,” said John H. Alexander, M.D., Principal Investigator of the APPRAISE-1 study, Duke Clinical Research Institute and Duke Heart Center in Durham, North Carolina.

The six-month APPRAISE-1 study was not powered to demonstrate significance on the composite efficacy endpoint of cardiovascular death, non-fatal heart attack, severe recurrent ischemia and non-hemorrhagic stroke. However, there was a non-significant relative risk reduction compared to placebo (n=611) of 27 percent for 2.5 mg twice daily (n=317) and 39 percent for 10 mg once daily (n= 318) doses.

The incidence of the primary endpoint of this safety study, major bleeding plus clinically relevant non-major bleeding, was 5.7 percent for apixaban patients who took the 2.5 mg twice daily dose (n=315), 7.9 percent for patients who took the 10 mg once daily dose (n=315), and 3.0 percent for patients who took placebo (n=599). The bleeding scale used in the APPRAISE-1 trial was the comprehensive International Society of Thrombosis and Haemostasis (ISTH) standard. The incidence of major ISTH bleeding was 0.8 percent with placebo (n=599) versus 1.6 and 1.9 percent with the 2.5 mg twice daily (n=315) and 10 mg once daily (n=315) doses, respectively. Results for major bleeding measured using the more commonly used TIMI scale, in a post-hoc assessment, were 0.3 percent (n=599) for placebo, 0.0 percent (n=315) for the 2.5 mg twice daily apixaban dose and 1.0 percent (n= 315) for the 10 mg once daily apixaban dose. Two additional arms of the study that examined higher doses, 10 mg twice daily and 20 mg once daily, were stopped early due to increased total bleeding.

The incidence of adverse events, serious adverse events and discontinuations due to adverse events was similar for all treatment groups. The discontinuation rates for bleeding events were 1.2 percent with placebo, 1.9 percent with the 2.5 mg twice daily dose and 2.9 percent with the 10 mg once daily dose. The incidence of liver function test abnormalities following six-month dosing was similar with apixaban and placebo.