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

• Idarucizumab, which was granted Breakthrough Therapy Designation by FDA, was shown to restore the blood clotting mechanism in healthy volunteers1,2
• This is the first time that such an effect was shown in humans for an NOAC antidote
• RE-VERSE AD™ Global Phase III study in patients in the clinical setting already initiated in 29 countries worldwide

Ingelheim, Germany, 19 November 2014 – 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.3

NOTES TO THE EDITORS

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) equates to over 3 million patient-years in all licensed indications worldwide. Pradaxa® has been in the market for more than 6 years and is approved in over 100 countries.4

Currently approved indications for Pradaxa® are:5,6

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and a risk factor for stroke
  • Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery or total knee replacement surgery
  • Treatment of DVT and PE and the prevention of recurrent DVT and recurrent PE in adults

Pradaxa®, a direct thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.7 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.8 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or mandatory dose adjustment.7,9

Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Taking social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative "Making more Health" and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% of its net sales.

For more information please visit www.boehringer-ingelheim.com

* 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.
5.Pradaxa® European Summary of Product Characteristics, 2014.
6.PRADAXA US Prescribing Information, 2014.
7.Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
8.Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
9.Stangier J. et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.

 

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