Boehringer Ingelheim submits applications for approval of idarucizumab*, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada 

  • First submission of an investigational specific reversal agent to a novel oral anticoagulant (NOAC) for regulatory approval
  • Boehringer Ingelheim pursues accelerated procedures with all three authorities1
  • In Phase I, idarucizumab has shown immediate, complete and sustained reversal of the anticoagulant effect of dabigatran (Pradaxa®)2

Boehringer Ingelheim today announces that idarucizumab has been submitted for approval of marketing authorisation to the European Medicines Agency (EMA), U.S. Food and Drug Administration (FDA) and Health Canada.1 The submission is for use in patients who require rapid reversal of the anticoagulant effect of dabigatran, the active ingredient in Pradaxa®.

“The submissions for idarucizumab mark the first regulatory submissions for a specific reversal agent to a novel oral anticoagulant,” said Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Our discovery and development of idarucizumab in-house is an example of our company’s dedication to the evolution and innovation of anticoagulation care. Idarucizumab is being developed to provide physicians with a specifically targeted reversal agent for Pradaxa® patients in rare emergency situations.”

Idarucizumab was granted Breakthrough Therapy Designation by the U.S. FDA.3 Boehringer Ingelheim pursues accelerated procedures with all three regulatory authorities.1

The submissions to the EMA, FDA and Health Canada are based on the results from clinical trials of idarucizumab in volunteers, including elderly and renally impaired individuals.1,2,4 Phase I data showed an immediate, complete and sustained reversal of the anticoagulant effect of dabigatran following the administration of idarucizumab and no pro-thrombotic effect.2 The submissions also include first interim data from the ongoing RE-VERSE ADTM study. RE-VERSE ADTM is an ongoing global Phase III patient study in which Boehringer Ingelheim continues to evaluate idarucizumab in patients treated with Pradaxa® who are in need of emergency intervention, or experience an uncontrolled or life-threatening bleeding event.5

NOTES TO THE EDITORS

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) equates to over 3.9 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.1

Currently approved indications for Pradaxa® are:6,7

  • 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.8 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.9 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.8,10

References

1. Boehringer Ingelheim Data on File.
2. Glund S, et al. A specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in healthy male volunteers. American Heart Association Scientific Sessions, Dallas, TX, USA, 16-20 November 2013, abstract 17765.
3. 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 March 2015.
4. Glund S. et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects. Presented on 8th December at the 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA. Available at: https://ash.confex.com/ash/2014/webprogram/Paper74960.html Last accessed March 2015.
5. Pollack C, et al. A Phase III Clinical Trial to Evaluate the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD™). International Stroke Conference, Nashville, TN, USA, 11-13 February 2015, Poster presentation.
6. Pradaxa® European Summary of Product Characteristics, 2014.
7. PRADAXA® US Prescribing Information, 2014.
8. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
9. Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
10. 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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