New data show dabigatran-specific antidote idarucizumab* restores blood clotting mechanism in humans

New data on the investigational antidote idarucizumab show that it can reverse the effect of the oral anticoagulant Pradaxa® (dabigatran etexilate) on both blood coagulation and the blood clotting mechanism. In a study in healthy volunteers, administration of idarucizumab after initial pre-treatment with Pradaxa® was shown to restore systemic blood coagulation and re-enable the formation of fibrin, a key component of the blood clotting mechanism.¹ This is the first time that an antidote to a novel oral anticoagulant (NOAC) has demonstrated such an effect. The findings were presented during the American Heart Association’s Scientific Sessions 2014. 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,” said Joanne van Ryn, Ph.D., Department of CardioMetabolic Disease Research, Boehringer Ingelheim. “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 Pradaxa®, and after subsequent administration of idarucizumab or placebo. The results showed that Pradaxa® 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.¹

“With the development of the dabigatran-specific antidote Boehringer Ingelheim continues to advance anticoagulation therapy, demonstrating our commitment to research and scientific innovation” said Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim. “The specific investigational antidote for Pradaxa®, which our scientists at Boehringer Ingelheim are developing, would give physicians an additional and highly targeted option beyond the already existing measures for treatment in clinical situations where patients might benefit from an immediate reversal of the anticoagulant effect of dabigatran.”

In June 2014, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to the dabigatran etexilate specific investigational antidote.²

RE-VERSE AD™, a global patient study, has been underway since May 2014 to investigate the antidote in the clinical setting in patients taking Pradaxa® who have uncontrolled bleeding or require emergency procedures. The study will be open to eligible patients in more than 35 countries and was recently also initiated in the US. 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.⁴

* Idarucizumab is the recommended International Nonproprietary Name (INN).

References

1. van Ryn J. et al. Effect of Dabigatran on the Ability to Generate Fibrin at a Wound site and its Reversal by Idarucizumab, the Antidote to Dabigatran, in Healthy Volunteers: An Exploratory Marker of Blood Loss. Presented on 18th November at the American Heart Association Scientific Sessions 2014, Chicago, USA. Available at: http://www.abstractsonline.com/pp8/#!/3547/presentation/41579
2. Boehringer Ingelheim Press Release – 30 June 2014. U.S. FDA grants Breakthrough Therapy Designation to Pradaxa® (dabigatran etexilate) specific investigational antidote. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/30_june_2014_dabigatranetexilate.html Last accessed November 2014.
3. Boehringer Ingelheim Press Release – 22 May 2014. Antidote for rapid reversal of Pradaxa® (dabigatran etexilate) progresses into next stage of clinical investigation with study in patients. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/22_may_2014_dabigatranetexilate.html; Last accessed November 2014.
4. Boehringer Ingelheim data on file.