More information from a large clinical trial of apixaban is needed before the Food and Drug Administration can move forward in reviewing the oral anticoagulant for preventing stroke and systemic embolism for approval in patients with nonvalvular atrial fibrillation, according to a statement issued by Bristol-Myers Squibb on June 25.
Apixaban, a factor Xa inhibitor, is being reviewed by the FDA for this indication, but the agency has issued a complete response letter requesting "additional information on data management and verification from the ARISTOTLE trial," one of the two large studies submitted to the FDA for the approval of this indication, the statement said. No other details were provided.
The other large clinical trial submitted in support of this indication is the AVERROES (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) study, which along with the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, compared apixaban to warfarin or aspirin in almost 24,000 patients with atrial fibrillation. The results of both trials were published last year in the New England Journal of Medicine.
The FDA issues complete response letters to companies when there are outstanding issues that need to be resolved before the drug is approved. The FDA does not announce when these letters are issued, but the manufacturers often do.
The FDA has not asked for any new studies, and Bristol-Myers Squibb and Pfizer, which are collaborating to develop and commercialize apixaban in the United States and internationally, plan to work closely with the FDA on the next steps for the application, the statement said.
If approved in the United States, apixaban will be marketed as Eliquis, its trade name in the European Union, where it was approved in May 2011 for the prevention of venous thromboembolic events (VTEs) in adult patients who have undergone elective hip or knee replacement surgery. It is also under review for the atrial fibrillation indication in the European Union and Japan, the statement said.
In the ARISTOTLE study of patients with atrial fibrillation and at least one other stroke risk factor, apixaban was superior to warfarin in preventing stroke or systemic embolism, and was associated with less bleeding and lower mortality (N. Engl. J. Med. 2011;365:981-92). In the AVERROES study, apixaban was associated with a reduced risk of stroke or systemic embolism, but it did not significantly increase the risk of major bleeding or intracranial hemorrhage (N. Engl. J. Med. 2011;364:806-17).
The statement adds that the companies plan to conduct studies of almost 60,000 patients worldwide for different indications and patient populations, including nine phase III studies that have either been completed or are still underway. It is being studied as a treatment for VTE in the phase III studies.