FDA Approves Praxbind® (idarucizumab), Specific Reversal Agent for Pradaxa® (dabigatran etexilate)

  • First FDA approval of a specific reversal agent for a novel oral anticoagulant (NOAC)1
  • Praxbind® immediately reverses the anticoagulant action of dabigatran2,3

Ingelheim, Germany, 19. October 2015 – Boehringer Ingelheim GmbH announced the U.S. Food and Drug Administration (FDA) granted approval of Praxbind® (idarucizumab).4 Praxbind® is indicated for patients treated with Pradaxa® (dabigatran etexilate), when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding.

"We are very pleased to offer Praxbind®, the first specific reversal agent for a novel oral anticoagulant, now approved by the FDA," said Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. "With this approval, Boehringer Ingelheim is again leading the evolution of anticoagulation care, as we did with the introduction of Pradaxa®. While we anticipate that Praxbind® will be rarely used in clinical practice, the availability of a specific reversal agent has the potential to give physicians and patients added confidence in choosing Pradaxa®."

The FDA granted Praxbind® Breakthrough Therapy Designation and the application received Priority Review.5 Praxbind® was approved under an Accelerated Approval Pathway.6 The application included data from healthy volunteers as well as results from an interim analysis of the RE-VERSE AD™ trial (NCT 02104947).2,3,7,8 In the studies, the reversal effects of Praxbind® were evident immediately, within minutes after administration of 5 grams of Praxbind®.2,3,7,8 No procoagulant effect was observed after the administration of Praxbind®.2,3,7

"The emergence of novel oral anticoagulants, or NOACs, marked a significant advancement in anticoagulation care. While general management strategies for NOAC-related bleeding are available, until today, there was no option for specific and immediate reversal of the anticoagulant effect of a NOAC in a patient in rare emergencies where speed matters, such as life threatening bleeding or the need to quickly perform surgery or interventions," said Dr. Charles Pollack, lead investigator of RE-VERSE AD™, Professor of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA. "The availability of Praxbind® now provides a unique option for reversing anticoagulation in patients taking Pradaxa®."

Boehringer Ingelheim is committed to making Praxbind® available as widely as possible. Praxbind® is currently being assessed by different regulatory authorities, including Health Canada.6 Further submissions are ongoing.4

NOTES TO THE EDITORS

About the Praxbind® Clinical Trial Programme
Praxbind® was discovered and developed by Boehringer Ingelheim scientists.4 The research programme was initiated in 2009, before Pradaxa® was launched in the U.S. in 2010.4,9

The company completed three phase I trials of Praxbind® in human volunteers, and included these data in the Praxbind® biologics license application (BLA) it submitted to the U.S. Food and Drug Administration.4,6-8

Boehringer Ingelheim is continuing to evaluate Praxbind® in RE-VERSE AD™, a phase III global study that includes patients taking Pradaxa® who have uncontrolled bleeding or require emergency procedures.2,10 The study is the first of its kind in patients, and has been underway since May 2014, enrolling patients in more than 35 countries.11 Data from an interim analysis from RE-VERSE AD™ was also included in the Praxbind® application.2,3,6

About Praxbind®
Praxbind® is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.10 Praxbind® binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.10

In the US, Praxbind® is now indicated in patients treated with Pradaxa® when reversal of the anticoagulant effects of dabigatran is needed:1

  • For emergency surgery/urgent procedures
  • In life-threatening or uncontrolled bleeding

Regulatory reviews and submissions in other countries are ongoing.4,6 Praxbind® is the only specific reversal agent for a NOAC currently in regulatory review.4 Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.4

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

Currently approved indications for dabigatran are:9,12

  • 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

Dabigatran, 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.12,13 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.14 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, dabigatran 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.13,15

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.

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Referências

  1. PRAXBIND® US Prescribing Information, 2015
  2. Pollack C. V. et al. Idarucizumab for dabigatran reversal. NEJM. 2015 June 22 (Epub ahead of print). Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1502000
  3. Pollack C.V. Initial results of the RE-VERSE AD trial: idarucizumab reverses the anticoagulant effects of dabigatran in patients in an emergency setting of major bleeding, urgent surgery, or interventions. Oral presentation on Monday 22 June 2015 at the International Society of Thrombosis and Haemostasis 2015 Congress, Toronto, Canada.
  4. Boehringer Ingelheim Data on File.
  5. Boehringer Ingelheim Press Release – 30 June 2014. U.S. FDA grants Breakthrough Therapy Designation to Pradaxa® (dabigatran etexilate) specific investigational antidote.
    /press-release/us-fda-grants-breakthrough-therapy-designation-pradaxa-dabigatran-etexilate-specific Last accessed August 2015.
  6. Boehringer Ingelheim Press Release – 03 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 August 2015.
  7. Glund S. et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113:943–951.
  8. 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. Oral presentation on 8 December 2014 at The 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA. Blood 2014; 124: Abstract 344.
  9. PRADAXA US Prescribing Information, 2015
  10. Pollack C. V. et al. Design and rationale for RE-VERSE AD: A phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost. 2015 May 28;114(1). http://th.schattauer.de/en/contents/archive/issue/2232/manuscript/24418.html.
  11. Boehringer Ingelheim Press Release – 22 May 2015. Antidote for rapid reversal of Pradaxa® (dabigatran etexilate) progresses into next stage of clinical investigation with study in patients. http://www.boehringer-ingelheim.com/press-release/antidote-rapid-reversal-pradaxa-dabigatran-etexilate-progresses-next-stage-clinical Last accessed August 2015.
  12. Pradaxa European Summary of Product Characteristics, 2015.
  13. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  14. Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  15. 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