The US approval late last year of the blood thinner Eliquis (apixaban) made it the third blood-thinner pill option to come online in the last three years, all of which have proven to be as or more effective as the old go-to warfarin, with lower rates of brain hemorrhaging and fewer blood tests required to get the dosing right. However, unlike warfarin, which has an antidote in the form of vitamin K, no compounds exist that directly counteract the anticoagulation effects of these next-generation blood thinners—something desperately needed for the 1–3% of patients who suffer major bleeding complications, experience trauma injuries or require urgent surgery while on these pills.
New anticoagulation antidotes could be on the way. On 5 February, Portola Therapeutics, a South San Francisco–based company with an injectable antidote called PRT064445, announced that it had sealed a deal with Germany’s Bayer and New Jersey’s Janssen Pharmaceuticals to test PRT064445 in a phase 2 trial involving healthy volunteers given Xarelto (rivaroxaban). This pact comes on top of a similar partnership announced in November 2012 between Portola and the makers of Eliquis, Bristol-Myers Squibb and Pfizer, both based in New York.
Approved by the US Food and Drug Administration in 2011, Xarelto, like Eliquis, blocks a key enzyme in the blood-clotting cascade called factor Xa. PRT064445 works by acting as a decoy for drugs like Eliquis and Xarelto to bind to, preventing them from obstructing factor Xa in the bloodstream.
Reporting online today in Nature Medicine, Portola scientists showed in human plasma that PRT064445 reversed the anticoagulant effects of these drugs and another experimental factor Xa targeted agent known as betrixaban, as well as two indirect factor Xa inhibitors, including a form of heparin, an older injectable anticoagulant. The drug also restored normal clotting in rabbits and rats. According to John Curnutte, head of research and development at Portola, based in South San Francisco, California, PRT064445 also proved safe and well tolerated in an as-yet-unpublished phase 1 study involving 32 healthy volunteers not on anticoagulant therapy.