Boehringer Ingelheim’s Interim Phase III Data: 5g dose of idarucizumab immediately reversed the anticoagulant effect of dabigatran in all patients evaluated

• A single 5g dose of idarucizumab immediately reversed the anticoagulant effect of dabigatran in all patients evaluated
• Results based on analyses of high-risk patients from RE-VERSE AD™ study
• Data presented at ACC 2016 Scientific Session and Expo

Ingelheim, Germany, 08-Apr-2016 — /EuropaWire/ — Boehringer Ingelheim has announced the results of a new interim analysis of data from the ongoing phase III RE-VERSE AD™ patient study that showed a single 5g dose of idarucizumab immediately reversed the anticoagulant effect of dabigatran, the active ingredient in Pradaxa® (dabigatran etexilate), in all patients evaluated.1 Idarucizumab was the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant approved by Regulatory Authorities including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2015, and is marketed as Praxbind®.2,3 The results from this study were presented at the American College of Cardiology 65th Annual Scientific Session (ACC.16) and Expo in Chicago.1

“The data from this new RE-VERSE AD™ interim analysis of the first 123 patients support earlier findings that show idarucizumab reverses the anticoagulant effect of dabigatran, including reversal in critically ill, high-risk patients in emergency care,” said Dr. Charles Pollack, lead investigator of RE-VERSE AD™, Professor of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, USA. “We have enrolled patients in more than 35 countries and we look forward to the additional analyses and final results to further support the safety, effectiveness and impact of idarucizumab.”

RE-VERSE AD™ was designed to allow for the types of patients healthcare professionals may treat in real-world emergency settings.4 Patients were categorised into two groups – (A) patients with uncontrolled or life-threatening bleeding complications (Group A, n=66), or (B) patients requiring emergency surgery or an invasive procedure (Group B, n=57).1,4 All patients received 5g of idarucizumab, and reversal was evident in all assessable patients (n=100).1

Among assessed patients in Group A (n=48), the median subjective investigator-reported time to cessation of bleeding was 9.8 hours. In Group B (n=52), the mean time to surgery was 1.7 hours following administration of idarucizumab. Normal blood clotting (haemostasis) during surgery was reported in 92 per cent of patients (48/52). Thrombotic events occurred in five patients between two to 24 days after idarucizumab administration. None of these patients were receiving antithrombotic therapy at the time of their event. There were 26 total deaths, which appeared to be related to the original reason for emergency admission to the hospital and/or to co-morbidities.1

“These new data add to the body of evidence for idarucizumab and the important role it will play for patients. While emergency situations in which idarucizumab may be used are rare, we are convinced that offering a broadly available specific reversal agent will set a new level of care for patients, caregivers and healthcare providers,” said Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Boehringer Ingelheim is committed to bringing value to patients through investment in innovation. The research, development and regulatory approvals of idarucizumab, the first specific reversal agent for a non-vitamin K antagonist oral anticoagulant, are evidence of this commitment.”

NOTES TO THE EDITORS

About the RE-VERSE AD™ study
RE-VERSE AD™ is an ongoing phase III global study that includes patients taking dabigatran who require urgent procedures or have uncontrolled bleeding.4 The interim analysis from RE-VERSE AD™ included data from patients requiring urgent procedures / emergency surgery, e.g. surgery for an open fracture after a fall, or patients with either uncontrolled or life-threatening bleeding complications, e.g. intracranial haemorrhage or severe trauma after a car accident.1,4 The primary endpoint, the degree of reversal of the anticoagulant effect of dabigatran achieved by idarucizumab within four hours, was measured by diluted thrombin time (dTT) and ecarin clotting time (ECT).4

The study is the first of its kind in patients, and has been underway since May 2014, enrolling up to 500 patients in more than 35 countries.1.5

About idarucizumab (Praxbind®)
Idarucizumab is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.6 Idarucizumab binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.4,6

In the EU and U.S., idarucizumab is now indicated for patients treated with dabigatran when reversal of the anticoagulant effects of dabigatran is needed:2,3

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

Regulatory reviews and submissions in other countries are ongoing. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.7

About dabigatran etexilate (Pradaxa®)
Clinical experience of dabigatran equates to over 5 million patient-years in all licensed indications worldwide. Dabigatran has been in the market for more than 7 years and is approved in over 100 countries.7

Currently approved indications for dabigatran are:8,9

  • 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.8-10 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.11 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.10,12

Dabigatran is the only non-vitamin K antagonist oral anticoagulant with an approved reversal agent. Praxbind® (idarucizumab) is approved in the EU and U.S. for adult patients treated with Pradaxa® who require rapid reversal of its anticoagulant effects prior to urgent procedures/emergency surgery or in life threatening or uncontrolled bleeding.2,3

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.

References
1. Pollack C.V et al. Idarucizumab for Reversal of the Anticoagulant Effects of Dabigatran in Patients in an Emergency Setting of Major Bleeding, Urgent Surgery, or Interventions. 1130M-05. Presented on 2 April 2016 at the American College of Cardiology 65th Annual Scientific Session and Expo, Chicago.
2. Praxbind® U.S. Prescribing Information, 2015.
3. Praxbind® European Summary of Product Characteristics, 2015.
4. 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;114(1):198-205.
5. 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 April 2016.
6. Schiele F. et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121(18):3554–62.
7. Boehringer Ingelheim Data on File.
8. Pradaxa® European Summary of Product Characteristics, 2016.
9. Pradaxa® U.S. Prescribing Information, 2015.
10. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
11. Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353(10):1028–40.
12. 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(5):555–63.

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