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Pfizer and Bristol-Myers Squibb presented data at the European Society of Cardiology Congress from a late-stage trial which demonstrated that Eliquis (apixaban) significantly reduced the risk of stroke or systemic embolism, major bleeding, and mortality compared to warfarin. Former president of the American College of Cardiology Ralph Brindis called the study, top-line data from which were presented in June, a "home run," adding that "it is another dagger in the heart for warfarin as an anticoagulation treatment for patients with atrial fibrillation to prevent stroke."

The ARISTOTLE trial, results from which were also published in the NEJM, randomised 18 201 patients with atrial fibrillation and at least one additional risk factor for stroke to receive Eliquis twice daily or warfarin given to achieve a target International Normalized Ratio of 2.0-3.0. Data showed that patients in the Eliquis arm had a 21-percent reduced risk of stroke or systemic embolism, a 31-percent reduced risk of major bleeding and a 11-percent reduced risk of mortality, versus warfarin. Based on these data, the researchers calculated that for every 1000 patients treated with Eliquis instead of warfarin for 1.8 years, which was the average length of the study, stroke would be avoided in 6 patients, major bleeding would be avoided in 15 patients, and death would be avoided in 8 patients. In addition, Eliquis met a key secondary endpoint by demonstrating superiority for the outcome of stroke and systemic embolism, including a 49 percent lower risk of haemorrhagic stroke and a 8 percent lower risk of ischemic or uncertain stroke with Eliquis versus warfarin.

Comparing the data to the RE-LY trial of Boehringer Ingelheim’s Pradaxa (dabigatran), the study authors wrote that Eliquis "appears to combine the advantages of each of the two doses of [Pradaxa], with both a greater overall reduction in the rate of stroke and a lower rate of bleeding than the rates with warfarin." They also noted that in the ROCKET AF trial, Bayer and Johnson & Johnson’s Xarelto (rivaroxaban) lowered intracranial haemorrahge and fatal bleeding, but was not better than warfarin in other major bleeding. However, the researchers noted that the differences in outcomes in the various trials of the three drugs could be due to "differences in the doses of drugs, the pharmacokinetic and pharmacodynamic properties of the drugs, patient populations, or other features of the clinical-trial design."

In an accompanying editorial, Jessica Mega called the ARISTOTLE results "impressive" and noted that "a new era of anticoagulation in patients with atrial fibrillation appears to be emerging." However, she warned that it is too early to say which of the new agents will lead the market until head-to head trials of the various agents have been performed. "The nuances between them will be teased out" in further study and as they are used by clinicians, she noted.

Currently, analysts expect 2015 sales of $1.6 billion for Eliquis. The figure is less than the $3 billion forecast for Xarelto, although Barclays Capital analyst Tony Butler said he believes Eliquis will become the top-selling anti-coagulant, with peak annual sales eventually reaching $5 billion. Lead ARISTOTLE author Chris Granger noted that cost is likely to be the "biggest single barrier" to use of any of the new agents, with Pradaxa priced at $6.75 for a twice-a-day dose, versus warfarin, which is available for pennies a day.

Pfizer and Bristol-Myers Squibb expect to file for approval of Eliquis in the US this year. The product is currently approved in the EU for use in preventing venous thromboembolic events (VTE) in adults who have undergone elective hip or knee replacement surgery.