Correction: A previous version of this article misrepresented sales of Xarelto over the first six months of 2016. Sales of Xarelto by Johnson & Johnson totaled $1.2 billion in the U.S. over that period, while Bayer separately reported sales in other markets.
- Portola Pharmaceuticals on Tuesday touted positive interim results from a real-world study of its anticoagulant reversal agent, two weeks after the company revealed the Food and Drug Administration had refused to approve the drug due to issues related to manufacturing.
- Data from the Phase 3b/4 trial of Andexxa (andexanet alfa), a Factor Xa inhibitor antidote, showed treatment with the drug effectively stopped bleeding in 79% of patients who presented with an acute major bleed while on a Factor Xa inhibitor.
- There is currently no FDA-approved antidote to Factor Xa inhibitors, which include Bristol-Myers Squibb's rapidly growing Eliquis (apixaban) and Johnson & Johnson's Xarelto (rivaroxaban). Given the unmet medical need, Portola's development of Andexxa has been closely followed.
News of the positive results did little to lift Portola's stock, which shed over a quarter of its value in the three days following announcement of the complete response letter (CRL) from the FDA on August 17.
Portola had filed for approval of Andexxa on the basis of two Phase 3 trials evaluating the reversal agent in older healthy patients taking either Xarelto or Eliqius. But the FDA apparently had problems with Portola's approach to manufacturing, requesting more information in the CRL. Regulators also asked for more data supporting Andexxa's efficacy as an antidote to edoxaban and enoxaparin, which Protola sought to include on Andexxa's label.
Safety data from initial patients enrolled in the Phase 3b/4 study was also included in that initial application. Now, Portola has more data from that trial, which involved patients presenting to a hospital or center with a major bleed rather than the healthy volunteers recruited for the previous two studies.
Preliminary analysis looked at 67 patients, 47 of whom were evaluated for efficacy. Following bolus administration of Andexxa, median anti-Factor Xa activity dropped by 89% from baseline in patients on Xarelto and by 93% among those taking Eliquis. Over the 12-hour period following infusion, 79% of those 47 patients achieved "excellent or good" hemostasis, according to the company.
During 30-day follow-up, thrombotic events occurred in 12 patients and death in 10 patients, which the company said was within an expected range given the severity of the bleeding episodes.
A data and safety monitoring board recommended the study proceed as planned. Meanwhile, Portola is working with the FDA to determine the next steps for approval of Andexxa, but a timeline remains unclear at this point.
Bristol-Myers and J&J have invested heavily in advertising their new anticoagulant treatments, seeking to encourage doctors to prescribe them over the standard warfarin. But the lack of a reversal agent raises the risk of uncontrollable bleeding, even though Factor Xa inhibitors have a lower risk of intracranial hemorrhage compared to warfarin.
Portola's Andexxa would meet that need and could have a substantial market opportunity, if approved. Success of Andexxa would also give a boost to sales of Eliquis, Xarelto and other Factor Xa inhibitors.
Even without an antidote, revenue from Eliquis surpassed $1.5 billion over the first six months of 2016. Sales of Xarelto in the U.S., where it is marketed by Johnson & Johnson,totaled $1.2 billion during the same period. Bayer, which sells Xarelto in markets outside the U.S., recorded about $1.5 billion in revenue over that stretch of time.
Before the recent CRL setback, approval of Boehringer Ingelheim's Praxbind, a reversal agent for Boehringer's Pradaxa, last October had taken some of the wind out of Portola's sales. While Pradaxa is not a Factor Xa inhibitor, it was the first reversal agent approved for a new anticoagulant. Portola's stock has declined steadily since last December.
Interim results from the Phase 3b/4 study of Andexxa were first published in The New England Journal of Medicine and can be viewed here.