The FDA has issued a complete response letter for the New Drug Application (NDA) for the direct factor Xa inhibitor apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF).
The agency has requested additional information on data management and verification from the ARISTOTLE trial, but is not calling for new studies, the companies reported. The ARISTOTLE and AVERROES trials have evaluated apixaban in approximately 24,000 patients with AF, including patients who are expected or demonstrated to be unsuitable for vitamin K antagonist therapy.
ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) found that apixaban reduced the risk of stroke or systemic embolism by 21 percent, major bleeding by 31 percent and death by 11 percent. AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes) results showed that apixaban significantly reduced the risk of stroke or systemic embolism without increasing the risk of major bleeding or intracranial hemorrhage in AF patients. AVERROES was stopped early, based on the beneficial findings.
Apixaban is not approved for the prevention of stroke or systemic embolism in patients with AF in any country. In May 2011, Bristol-Myers Squibb and Pfizer announced the first regulatory approval for apixaban in the 27 countries of the European Union for the prevention of venous thromboembolic events in adult patients who have undergone elective hip or knee replacement surgery.
In February of this year, the companies announced that the FDA had extended the action date for the apixaban NDA for prevention of stroke and systemic embolism in patients with atrial fibrillation by three months to June 28, based on a major amendment to the NDA.
Princeton, N.J.- based Bristol-Myers Squibb and New York City-based Pfizer are collaborating on the development and commercialization of apixaban, an investigational oral anticoagulant discovered by Bristol-Myers Squibb.