Positive interim results for AndexXa (andexanet alfa)showed reversal of anti-Factor Xa activity.-Portola Pharma

Portola Pharmaceuticals Inc.announced interim results from the ongoing Phase IIIb/IV ANNEXA-4 study of AndexXa (andexanet alfa), a Factor Xa inhibitor antidote. In this study of patients with Factor Xa inhibitor-associated acute major bleeding, a preliminary analysis of interim data from 67 patients (of whom 47 were evaluated for efficacy) showed that AndexXa rapidly and substantially reversed anti-Factor Xa activity (the anticoagulant mechanism of these drugs) when administered as a bolus, and sustained this reversal when followed by a 120-minute infusion. Additionally, 79 percent of these patients achieved excellent or good hemostasis (stoppage of bleeding) over a 12-hour period following infusion. These interim results were presented orally in a Late-Breaking Science Hot Line session at the European Society of Cardiology (ESC) 2016 Congress in Rome. The interim results were published simultaneously online by The New England Journal of Medicine (NEJM) and are accessible at http://investors.portola.com.

Factor Xa inhibitors are associated with a decreased risk of intracranial hemorrhage compared to warfarin, however the consequences are similar and can be fatal. In large randomized trials, the 30-day mortality rate in Factor Xa inhibitor patients with intracranial hemorrhage (ICH) exceeds 40 percent. The interim results from all 67 patients who received AndexXa showed that the antidote was not associated with any infusion reactions, and no patients developed antibodies to Factor Xa or Factor X or neutralizing antibodies to AndexXa. During the 30-day follow-up period, thrombotic events occurred in 12 patients (18 percent), and death occurred in 10 patients (15 percent). These events occurred within the range expected in this population given the severity of the bleeding, their underlying thrombotic risk, and the low percentage who restarted anticoagulant therapy following their bleeding episode.

Comment:On August 17, 2016, Portola received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for AndexXa. The Company plans to meet with the FDA as soon as possible in order to resolve the outstanding questions in the CRL and determine appropriate next steps. In the EU, Portola submitted a Marketing Authorization Application (MAA), which has been validated and is under review by the European Medicines Agency (EMA).