New data on the investigational antidote idarucizumab show that it may reverse the effect of the oral anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) on both blood coagulation and the blood clotting mechanism.
In a study in healthy volunteers, administration of idarucizumab after initial pre-treatment with dabigatran was shown to restore systemic blood coagulation and re-enable the formation of fibrin. A company press release states that this is the first time that an antidote to a novel oral anticoagulant (NOAC) has demonstrated such an effect.
The findings were presented by Joann van Ryn (Department of CardioMetabolic Disease Research, Boehringer Ingelheim) at an abstract/poster session at the American Heart Association’s Scientific Sessions (AHA; 15–19 November, Chicago, USA). The antidote is still under investigation and has not yet been approved for clinical use.
“These data are the first to show idarucizumab reverses dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism,” says van Ryn. “The findings from this sub-analysis complement earlier findings, which showed that idarucizumab provides immediate, complete and sustained reversal of the anticoagulation effect of Pradaxa with no associated procoagulant effects.”
In this sub-study of 35 healthy volunteers, fibrin formation was assessed after a small scratch, similar to a paper cut, was made: Measurements were conducted at baseline, after administration of dabigatran and after subsequent administration of idarucizumab or placebo. The results showed that dabigatran almost completely inhibited the fibrin formation at the wound site, and that idarucizumab restored fibrin formation. Idarucizumab was well tolerated and did not cause any clinically relevant side effects.
In June 2014, the US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to the dabigatran etexilate specific investigational antidote.
Idarucizumab is being investigated in the RE-VERSE AD global study, which includes patients taking dabigatran who have uncontrolled bleeding or require emergency procedures. The study has been underway since May 2014 and will be open to eligible patients in more than 35 countries. It was recently initiated in the USA. This is the first time that an antidote under development for a novel oral anticoagulant is investigated in a study in patients, instead of healthy volunteers, Boehringer Ingelheim states.