Boehringer Ingelheim has surpassed its rivals in the novel oral anticoagulant (NOAC) category by filing a reversal agent for its Pradaxa drug in Europe.
The antidote – called idarucizumab – allows patients taking Pradaxa (dabigatran) to have the drug’s anticoagulant effects switched off if they suffer a serious bleeding episode.
Thrombin inhibitor Pradaxa and other NOACs on the market – notably the Factor Xa inhibitors Xarelto (rivaroxaban) from Bayer and Johnson & Johnson (J&J), Pfizer/Bristol-Myers Squibb’s Eliquis (apixaban) and Daiichi Sankyo’s recently-approved Savaysa (edoxaban) – have started to replace vitamin K antagonists (VKAs) such as warfarin.
Their main advantage is they do not require complex dose titration and monitoring and have fewer interactions with food and other medicines, but a key downside is that unlike warfarin there is as yet no licensed antidote to reverse their effects.
Boehringer notes that the filing for idarucizumab in the EU, US and Canada is the first time that a NOAC antidote has reached this stage of development. The drug has also been awarded breakthrough status by the FDA and the company is aiming for accelerated review in all three markets.
In trials, a five-minute infusion of idarucizumab was able to reverse the blood thinning effects of Pradaxa (dabigatran) in young healthy volunteers, as well as in elderly people and patients with mild or moderate kidney impairment.
Antidotes are also being developed for Pradaxa’s rivals, with Portola Pharmaceuticals currently conducting phase III trials of andexanet alfa, which has been shown to reverse the effects of Eliquis, Xarelto and Savaysa, as well as the widely-used low-molecular weight heparin drug enoxaparin.
Portola has collaborations in place with the developers of all three Factor Xa inhibitors and also recently secured breakthrough status for tis drug from the US regulator. Meanwhile, Daiichi also said recently it is developing in-house reversal agents that can be used as antidotes if Savaysa causes bleeding complications.
If idarucizumab makes speedy progress to market it could give Pradaxa a lift in the NOAC category, where it is currently in third place after market leaders Xarelto and Eliquis.