Portola Pharmaceuticals ($PTLA) has laid out the last batch of Phase III data on its "breakthrough" anti-anticoagulant andexanet alfa, filling in the numbers that will be reviewed by regulators considering the biotech's upcoming pitch for marketing approval. And right alongside that announcement comes the latest numbers from Boehringer Ingelheim's breakthrough program for idarucizumab, which is already under review as an antidote to its blockbuster Pradaxa.
In the second part of their Phase III, Portola investigators say that andexanet reversed the anticoagulant activity of Eliquis (apixaban, sold by Pfizer [$PFE] and Bristol-Myers Squibb [$BMY]) by 93.5%. And the biotech says it is positioned to file for an accelerated approval later this year.
It was a small study. Of the 23 patients getting the treatment, there was a minimum reversal of anti-Factor Xa activity of 80%, plasma levels of the anticoagulant dropped significantly and thrombin generation was returned to normal. The investigators added that there were no serious adverse events in the study.
Their antidote--which earned the FDA's breakthrough therapy designation--is a molecule that is designed to latch onto Factor Xa inhibitors like Eliquis, disarming their activity when needed to prevent excessive bleeding. It is also being tested as an antidote for Xarelto.
Boehringer was equally bullish about its Phase III data for idarucizumab, now on the fast track at the FDA. Within hours of a 5-mg dose, investigators say the anticoagulant effect of Pradaxa was reversed in all patients. Within 12 hours, normal coagulant activity returned to 90% of patients.
These antidotes are expected to play a big role in determining who can gain and keep the largest market share for these next-gen anticoagulants. Boehringer got the first-mover advantage to the post-warfarin market with its approval of Pradaxa, but Eliquis and Xarelto have been coming on strong. All the manufacturers involved want to be able to guard against dangerous bleeding episodes that can occur, which makes these antidotes a major interest. And it appears that Boehringer once again is poised to come out a step ahead of its rivals.
"Importantly, our trial endpoints are based on the accepted pharmacodynamic measurements of anticoagulant activity agreed to with regulatory authorities and serve as the basis for our accelerated approval pathway," said John Curnutte, executive vice president, research and development for South San Francisco-based Portola, in a statement. "The results to date across our Phase II and Phase III andexanet alfa studies with both oral and injectable Factor Xa inhibitors suggest that andexanet alfa is the only investigational reversal agent to clinically show meaningful reversal of Factor Xa anticoagulant activity. There is an increasing number of patients on Factor Xa inhibitors who may need their anticoagulant reversed because they are bleeding or require surgery."
The data sets were presented today at the International Society on Thrombosis and Haemostasis 2015 Congress in Toronto.
- here's the release from Portola
- read the release from Boehringer