Two reversal agents for novel oral anticoagulants (NOACs) have aced clinical trials, setting them on course for regulatory approval.
Portola Pharmaceuticals and Bristol-Myers Squibb (BMS) has reported phase III data on its Factor Xa inhibitor antidote Annexa (andexanet alfa), showing it can effectively reverse the anticoagulant effects of Pfizer’s Eliquis (apixaban) by 94% when given as a bolus and two-hour infusion.
Meanwhile, Boehringer Ingelheim has reported more data from a 90-patient, real-world trial of its idarucizumab antibody, which shows it completely blocked the activity of the company’s thrombin inhibitor Pradaxa (dabigatran) – within minutes – in patients who needed reversal.
NOACs such as Eliquis and Pradaxa are increasingly being used in place of older drug such as warfarin because they are easier to administer and have a reduced risk of interactions with food and other medicines, but the lack of a reversal agent to block their activity in the event of bleeding side effects has been a concern.
Boehringer has already submitted idarucizumab for approval in the US, EU and Canada, taking the lead among companies developing antidotes for NOACs, which also include Factor Xa inhibitors Xarelto (rivaroxaban) from Bayer and Johnson & Johnson (J&J) and Daiichi Sankyo’s recently-approved Savaysa (edoxaban).
Earlier trials have also shown that andexanet alfa can reverse the effects of Xarelto and Savaysa, as well as the widely-used low-molecular weight heparin drug enoxaparin. Portola is collaborating with the companies developing all three of the Factor Xa inhibitors, while Daiichi Sankyo is also developing its own reversal agent.
It has been speculated that becoming first to have a reversal agent on the market will help Pradaxa capture market share from its rivals. It is currently third in the NOAC market behind Xarelto and Eliquis.
The new data means that Portola and BMS are now starting to catch up, with a filing in the US now planned before the end of the year.
Date from EvaluatePharma published earlier this year suggested the NOAC market will expand by 11.5% annually until it reaches $15.3bn in sales in 2018.