Bayer/Janssen seek Xa inhibitor antidote
pharmafile | February 6, 2013 | News story | Research and Development, Sales and Marketing | Bayer, Janssen, PRT4445, Xarelto
Bayer HealthCare and Janssen Pharmaceuticals have signed a deal with Portola Pharmaceuticals to evaluate the safety of an investigational antidote for Factor Xa inhibitors.
Portola’s PRT4445 is a novel recombinant protein designed to reverse anticoagulant activity in patients treated with that class of drugs and restore normal blood clotting.
In a proof-of-concept study, PRT4445 will be given to healthy patients who have already been administered the oral blood-thinner Xarelto (rivaroxaban), marketed by Bayer in Europe and Janssen in the US.
The programme is scheduled for completion in the second half of the year.
Portola is already fairly sure of its ground: at the European Society of Cardiology 2011 Congress, the company revealed pre-clinical study results showing that PRT064445 does indeed reverse Xarelto’s anticoagulant activity.
Xarelto itself works by blocking the blood clotting enzyme Factor Xa, but an antidote is clinically useful in situations where anticoagulants mean a patient is bleeding too much or uncontrollably, or where they are undergoing emergency surgery.
PRT4445 is similar to native Factor Xa but has been structurally modified to restrict its biological activity to reverse the effects of Factor Xa inhibitors.
It binds Factor Xa inhibitors in the blood, preventing them from stopping native Factor Xa acting in its normal way, which means that they can help in the process of blood coagulation.
Bayer and Janssen will make an upfront payment to Portola and will help with guidance on development and regulation, but Portola retains full global rights for PRT4445.
The new study will look at several doses in an attempt to see how useful the investigational compound is when it comes to reversing the effects of Xarelto.
Xarelto has a variety of licences and is NICE-approved to prevent strokes in patients with atrial fibrillation, and to help reduce the risk of blood clots in patients who have had knee or hip surgery.
“We are committed to exploring ways to expedite reversal of the drug’s effects when necessary, which could provide physicians with an additional treatment option during emergency situations,” said Larry Fields, Janssen’s senior director, clinical development, medical affairs.
In 2008 Portola presented in vivo proof of concept data showing that PRT064445 could act as a universal antidote for reversal of anticoagulation of all current Factor Xa inhibitors.
Two years later it demonstrated that PRT064445 can reverse the pharmacodynamic effects of anticoagulation by Sanofi’s injectable Lovenox (enoxaparin) and fondaparinux, both Factor Xa inhibitors.
It also showed that it could reduce the blood loss caused by these compounds in an animal model.
Venous thromboembolism (VTE) kills half a million people in Europe each year and drugs such as Xarelto – plus Pfizer and Bristol-Myers Squibb’s Eliquis and Boehringer’s Pradaxa – are all looking to dominate the oral anticoagulant market.
Adam Hill
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