New publication in The Lancet describes effective reversal of Pradaxa® in healthy volunteers

  • Specific reversal agent idarucizumab* led to immediate, complete and sustained reversal of Pradaxa® in healthy individuals
  • Complete reversal was achieved with a single five-minute infusion of idarucizumab which was well tolerated
  • Data now published are part of the ongoing regulatory review for approval of idarucizumab by the FDA, EMA and Health Canada

Ingelheim, Germany, 16 June, 2015 – Today, The Lancet published results from a healthy volunteer study investigating the reversal of the anticoagulant effect of Pradaxa® (dabigatran etexilate) by its specific reversal agent idarucizumab. The study showed that idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of Pradaxa®. The data support the specific reversal agent as a highly targeted treatment option if reversal of the anticoagulant effect is needed, e.g. for urgent interventions.1 Idarucizumab was granted Breakthrough Therapy Designation by the U.S. FDA2 and has recently been submitted for approval to the FDA, EMA and Health Canada.3 Boehringer Ingelheim pursues accelerated procedures with all three regulatory authorities.3

In the healthy volunteer study now published in The Lancet, participants first received Pradaxa® and then idarucizumab. The specific reversal agent was given two hours after the last dose of Pradaxa®, when dabigatran concentrations were at peak levels. After a five-minute infusion of idarucizumab, anticoagulation was immediately reversed back to baseline levels. The reversal effect was sustained for more than 24 hours for all doses of 2g and above. Idarucizumab was well tolerated by the study participants.1

“The data now published in The Lancet show in an impressive manner how effective idarucizumab was for reversing Pradaxa® in healthy volunteers”, said Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Once approved, the availability of a specific reversal agent for a NOAC will be yet another landmark in anticoagulation care.”

Similar results were also seen in elderly and renally impaired volunteers in a study presented at the Annual Meeting & Exposition of the American Society for Hematology in December 2014.4 Boehringer Ingelheim is now evaluating idarucizumab in the RE-VERSE ADTM study, the first study to investigate a reversal agent to a non-vitamin K antagonist oral anticoagulant in patients.5

NOTES TO THE EDITORS

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) equates to over 4 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.6

Currently approved indications for Pradaxa® are:7,8

  • 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.9 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.10 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.9,11

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 146 affiliates and a total of more than 47,700 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.

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 2014, Boehringer Ingelheim achieved net sales of about 13.3 billion euros. R&D expenditure corresponds to 19.9 per cent of its net sales.

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

This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

Referências

  1. Glund S, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. The Lancet. Published online June 16, 2015. Available at http://dx.doi.org/10.1016/S0140-6736(15)60732-2
  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/press-release/us-fda-grants-breakthrough-therapy-designation-pradaxa-dabigatran-etexilate-specific Last accessed April 2015.
  3. Boehringer Ingelheim Press Release – 3 March 2015. Boehringer Ingelheim submits applications for approval of idarucizumab, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada. http://www.boehringer-ingelheim.com/press-release/boehringer-ingelheim-submits-applications-approval-idarucizumab-specific-reversal Last accessed April 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 April 2015.
  5. Pollack C, et al. A Phase III Clinical Trial to Evaluate the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD™). Poster presentation at the International Stroke Conference, Nashville, TN, USA, 11-13 February 2015.
  6. Boehringer Ingelheim Data on File.
  7. Pradaxa® European Summary of Product Characteristics, 2014.
  8. PRADAXA US Prescribing Information, 2014.
  9. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  10. Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  11. 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.

Footnotes

* Idarucizumab is the recommended International Nonproprietary Name (INN). Idarucizumab is an investigational drug, which has not been approved for clinical use, and further safety and efficacy testing will be required.