FDA issues complete response letter for stroke indication for apixaban

FDA issued a complete response letter (CRL) for a New Drug Application (NDA) for apixaban (Eliquis, Bristol-Myers Squibb) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

If approved for stroke prevention, apixaban would compete against rivaroxaban (Xarelto, Janssen Research & Development) and dabigatran (Pradaxa, Boehringer Ingelheim), which were approved in November 2011 and October 2010, respectively.

The CRL requests additional information on data management and verification from the ARISTOTLE trial. A company press release stated that Bristol-Myers Squibb and Pfizer will work closely with FDA on the appropriate next steps for the apixaban application. FDA has not requested that the companies complete any new studies. FDA and the companies are committed to working expeditiously to address the outstanding questions and move the application forward.

“The companies believe they understand the information requested by the CRL,” Christina Trank, Bristol-Myers Squibb spokesperson, told Formulary. “FDA and the companies are committed to working expeditiously to address the outstanding questions and move the application forward. Per FDA regulation, the agency may take up to 6 months to review the companies’ response to the CRL. We are already working with the agency and we are hopeful that the review of our submission can be completed within a shorter time frame.”

"There is a significant unmet need to reduce the risk of stroke in patients with atrial fibrillation," Elliott Sigal, MD, PhD, executive vice president and chief scientific officer, Bristol-Myers Squibb, said in the press release. "We believe that the 2 large trials called ARISTOTLE and AVERROES have established the therapeutic profile for Eliquis and demonstrated a meaningful advance over the standard of care."

The companies continue to progress with the apixaban application for stroke prevention in atrial fibrillation in markets outside of the United States, including the European Union and Japan, based on the ARISTOTLE and AVERROES studies. These studies evaluated apixaban in approximately 24,000 patients with atrial fibrillation, including patients who are expected or demonstrated to be unsuitable for vitamin K antagonist therapy. The companies are committed to an ongoing clinical development program for apixaban, which is projected to include nearly 60,000 patients worldwide across multiple indications and patient populations and includes a total of 9 completed or ongoing, randomized, double-blind phase 3 trials.

For more on apixaban, click here.