Since 2010, the FDA has approved four novel oral anticoagulants. These drugs offer key benefits over the 60-year-old standard of care warfarin — including easier dosing regimens — but uptake of the newcomer drugs has been hampered by the inability to reverse their effects when clotting is needed; for example, after an accident or during emergency surgery. The FDA has now granted accelerated approval to Boehringer Ingelheim's idarucizumab, which acts as an antidote to the company's blood-thinning direct thrombin inhibitor dabigatran.

Idarucizumab is an antibody fragment that binds to dabigatran. In a 283-patient pivotal trial in healthy volunteers, it provided an immediate reduction in the amount of dabigatran in participants' blood that lasted for at least 24 hours. In another trial in 123 patients on dabigatran who needed to reverse its effects owing to uncontrolled bleeding or for emergency surgery, the anticoagulant effect of dabigatran was fully reversed in 89% of patients within 4 hours of administration of the antidote.

Other companies are working in this space as well. Portola Pharmaceuticals' Phase III andexanet alfa is a recombinant modified factor Xa molecule that acts as a decoy to clear factor Xa inhibitors such as Pfizer and Bristol-Myers Squibb's apixaban, Bayer's rivaroxaban and Daiichi Sankyo's edoxaban. Perosphere's small molecule aripazine is in Phase II trials to reverse the effects of factor Xa inhibitors and dabigatran.

These reversal agents could allay lingering concerns from patients and clinicians over the novel anticoagulants, providing a boost to the multibillion-dollar drugs (Nat. Rev. Drug Discov. 14, 5–6; 2015).