- Portola Pharmaceuticals Inc. stock fell almost 25% by market open Thursday on news the company may have to conduct another clinical trial for its Factor Xa inhibitor reversal agent AndexXa before the drug can gain U.S. approval.
- "[T]he request that's been made require[s] a randomized clinical trial, and then the expectation that we would have discussions over the review period," Portola CEO William Lis said during a Feb. 28 earnings call. Lis noted, however, the Food and Drug Administration has given limited information about the potential trial, and therefore his company is not changing AndexXa's expected launch date, set for May.
- AndexXa was initially rejected in August 2016. The company resubmitted the drug a year later and got a user fee action date of Feb. 3. The company informed investors in December that the potential approval date has since been pushed back to May 4.
Warfarin has long been the go-to blood thinner among prescribers, but the tides are starting to shift.
Johnson & Johnson and Bayer's Xarelto (rivaroxaban), Boehringer Ingelheim GmbH's Pradaxa (dabigatran), and Pfizer Inc. and Bristol-Myers Squibb Co.'s Eliquis (apixaban) are the first members in a class of next-generation drugs fittingly dubbed new oral anticoagulants (NOACs). They tout stronger efficacy profiles than warfarin and last year, for the first time, total prescriptions for the three NOACs outpaced the market share commanded by warfarin.
Even with those gains, warfarin is proving to be a tough competitor to edge out. That's partly because its blood-thinning effects can easily be reversed via vitamin K — a valuable characteristic in certain situations, such as when patients taking the drug need emergency surgery. Without those reversal agents, physicians were initially more hesitant to prescribe NOACs given the safety risks.
So far, Pradaxa is the only NOAC with an FDA-approved reversal agent, Praxbind (idarucizumab). Portola's looking to change that with AndexXa (andexanet alfa), which could serve as an antidote to Eliquis and Xarelto.
The FDA's apprehension, while frustrating for Portola and its investors, isn't completely unfounded. Reversal agents fall into the primary care market, meaning millions of patients could ultimately take AndexXa. As such, Portola's drug surely has to clear a very high bar for safety and efficacy should it stand a chance at getting approved.
But the road to market has been a bumpy one.
In August 2016, the FDA rejected AndexXa due to issues with the drug's manufacturing, proposed label and post-market clinical requirements. A year later, the agency agreed to review a revised Biologics License Application for AndexXa, and set a target action date of Feb. 3. As part of its discussions with regulators, Portola agreed to provide data on a usual care cohort that participated in the Phase 3 ANNEXA-4 study of AndexXa.
The saga didn't end there, however. Regulators pushed back the applications' target action date early this year, claiming they needed more time to review the new data added to it. Now, it appears the information package is still not enough to gain approval.
"[W]e had thought we ruled out a randomized clinical trial. We thought ... that the UCC was a reasonable compromise," Lis said.