Ingelheim, Germany, 22nd May, 2014 – Boehringer Ingelheim today announces the next step in the clinical development of idarucizumab*, the investigational antidote for rapid reversal of dabigatran-induced anticoagulation. The specific antidote has already demonstrated immediate, complete and sustained reversal of the anticoagulant effect of dabigatran in healthy volunteers.2 Now the potential antidote will be investigated in the clinical setting in patients taking Pradaxa® (dabigatran etexilate).1 This is the first time that an antidote under development for a novel oral anticoagulant is investigated in a study in patients.1
The development of the antidote (a humanized antibody fragment) is part of Boehringer Ingelheim’s commitment to advancing healthcare by broadening the range of reversal options available to physicians.3 The pivotal patient study will provide knowledge on the potential of the specific antidote to support the treatment of patients taking Pradaxa® who may benefit from rapid reversal of dabigatran-induced anticoagulation.1 A pivotal study traditionally is the last stage of clinical development of a medication.
Emergency rooms in more than 35 countries worldwide will participate in this study.1 Physicians will be equipped with the investigational antidote idarucizumab as a ‘ready to use’ solution for infusion.1 The first study sites in Europe have been initiated, and more sites and countries will follow during the course of the year.1
Prior clinical research of the antidote in a healthy volunteer study with 145 participants has already demonstrated the potential of the antidote for immediate, complete and sustained reversal of the anticoagulant effect of dabigatran.2 In the placebo-controlled study, the antidote was well tolerated and did not cause any clinically relevant side effects.2 Importantly, no pro-thrombotic effect was observed after the administration of the antidote and also no return of anticoagulant activity of dabigatran over time at adequate doses.2 These two aspects are especially valuable in clinical situations where rapid reversal of dabigatran-induced anticoagulation may be beneficial for patients taking Pradaxa®.
“For those patients who do need reversal, the antidote would provide an additional option beyond the already existing measures in a physician’s toolbox. The antidote would remove the anticoagulant effect of dabigatran from the clinical scenario so that physicians can focus on the other aspects of patient management.” said Dr. Charles Pollack, Professor of Emergency Medicine at the University of Pennsylvania School of Medicine and Chairman of Emergency Medicine at Pennsylvania Hospital in Philadelphia, USA and lead investigator of the patient study.
The antidote is still under investigation, has not been approved for clinical use, and further safety and efficacy testing will be required prior to market launch.
Boehringer Ingelheim is committed to scientific innovation and led the anticoagulant field by bringing Pradaxa® to patients worldwide. All studies in the RE-VOLUTION® clinical trial programme, which demonstrated the positive benefit-risk-profile of Pradaxa® and resulted in worldwide regulatory approvals, were conducted in the absence of an antidote.4-15 Pradaxa® is now benefiting patients in over 100 countries worldwide with clinical experience equating to over 2.9 million patient-years in all licensed indications.1
NOTES TO THE EDITORS
About Pradaxa® (dabigatran etexilate) Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 2.9 million patient-years in all licensed indications worldwide.1 Pradaxa® has already been in the market for more than 6 years and is approved in over 100 countries.1
Currently approved indications for Pradaxa® are:16
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and a risk factor for stroke
Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery
Primary prevention of venous thromboembolic events in patients undergoing elective total knee replacement surgery
A number of countries including the USA, have already approved Pradaxa® for patients with a deep vein thrombosis or a pulmonary embolism in the following indication:17
Treatment of deep vein thrombosis and pulmonary embolism
Prevention of recurrent deep vein thrombosis and pulmonary embolism
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.16,18 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.19 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 dose adjustment.18,20
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.
References 1Boehringer Ingelheim Data on File. 2Glund 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. 3Schiele F, et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121:3554-62. 4Ezekowitz MD, et al. RE-LY and RELY-ABLE Long-term Follow-up of Patients with Non-valvular Atrial Fibrillation Receiving Dabigatran Etexilate for up to 6.7 Years. Oral Presentation #10684 on Monday 18 November 2013 at the American Heart Association Scientific Sessions, Dallas, Texas, USA. 5Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. 6Connolly SJ, et al. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875-6. 7Connolly SJ, et al. The Long Term Multi-Center Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) study. Circulation. 2013;128:237-43. 8Eriksson BI, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007;370:949–56. 9Eriksson BI, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, doubleblind, non-inferiority trial. Thromb Haemost. 2011;105:721-9. 10Eriksson BI, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. Thromb Haemost. 2007;5:2178–85. 11Ginsberg JS, et al. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthoplasty. 2009;24:1–9. 12Schulman S, et al. Dabigatran versus warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med. 2009;361:2342–52. 13Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014;129:764-772. 14Schulman S, et al. Extended use of dabigatran, warfarin or placebo in venous thromboembolism. N Engl J Med. 2013;368:709–18. 15Oldgren J. et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32:2781-9. 16Pradaxa® European Summary of Product Characteristics 2014. 17PRADAXA Prescribing Information, 2014. Available at: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Last accessed: May 2014. 18Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95. 19Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40. 20Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabagitran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63