- After years of setbacks, Portola Pharmaceuticals has won U.S. approval of its Factor Xa inhibitor reversal agent Andexxa, avoiding further delays that investors feared the Food and Drug Administration might impose before granting an OK.
- Andexxa is an antidote of sorts to the new Factor Xa inhibitors Eliquis and Xarelto, undoing the blood-thinning effects of the drugs for patients with uncontrolled bleeding or who find themselves in life-threatening situations like emergency surgery.
- Shares in Portola spiked higher by more than 20% Friday morning on the news. With an approval now in hand, Portola plans to launch Andexxa on a limited basis in early June followed by a broader roll-out in early 2019.
With the FDA's decision, Andexxa [coagulation factor Xa (recombinant), inactivated-zhzo] becomes the first antidote approved to reverse the effects of Factor Xa inhibitors.
As use of the drugs has risen, more patients have been admitted to hospitals due to Factor Xa inhibitor-related bleeding. In 2016, more than 115,000 such cases were reported in the U.S., according to Portola.
Wafarin, a cheap generic blood-thinner, has maintained a substantial market share in part due to the availability of Vitamin K as an easy reversal agent. Physicians previously wary of prescribing the new oral anticoagulants due to the lack of a reversal agent will now have a new option to help manage their patients.
Importantly, though, the FDA OK only applies to use in patients treated with either Bristol-Myers Squibb and Pfizer's Eliquis (apixaban) or Johnson and Johnson and Bayer's Xarelto (rivaroxaban). Additionally, the label for the drug carries a black box warning for thromembolic risks, ischemic risks, cardiac arrests and sudden death — reflecting the potential adverse side effects of undoing anticoagulation in patients prescribed blood-thinners.
Andexxa's approval is a major relief to investors, whose hopes for the antidote were frustrated first by a three-month delay to the FDA's decision and then by news the regulator might require another clinical trial before approval.
Instead, Portola will need to conduct a randomized post-marketing study of Andexxa, set to begin in 2019 and conclude by 2023. Agreement from the regulator on that point, among others, opened the door for Andexxa's OK.
Andexxa's commercial launch will be limited at first, with drug product sourced from Portola's first-generation manufacturing process.
"Initial U.S. commercial supply of AndexXa will be sourced from our Gen 1 manufacturing process, and due to the limited supply in the first six months, we will focus on a limited number of hospitals to get Andexxa to patients who need it most," said Portola CEO William Lis on a Feb. 28 conference call with analysts.
Once it secures FDA approval for its "Gen 2" manufacturing, Portola will switch and launch Andexxa more broadly.
That element is particularly notable because the FDA initially rejected the drug in 2016 due, in part, to manufacturing-related issues.
Approval of Andexxa also gives Portola a complement to Bevyxxa (betrixaban), its own anticoagulant OK'd by the FDA last summer and launched in January.