New data show specific antidote idarucizumab reverses dabigatran-induced anticoagulation also in elderly and renally impaired volunteers

Ingelheim, Germany, 9 December 2014 – New data demonstrate that a five-minute infusion of the investigational specific antidote idarucizumab led to immediate, complete and sustained reversal of the anticoagulant effect of Pradaxa^® (dabigatran etexilate). In elderly individuals and those with mild or moderate kidney impairment, all doses of idarucizumab were found to be well tolerated. Dabigatran treatment could successfully be restarted 24 hours after the antidote had been administered, resulting in full re-anticoagulation.¹ The new data were presented today at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, San Francisco, USA. The specific antidote to dabigatran is still under investigation and has not yet been approved for clinical use.

“These results showed that idarucizumab consistently reversed the anticoagulant effects of dabigatran in adults independent of gender, age and kidney function, complementing data previously reported from younger, healthy male volunteers,” said Professor Jörg Kreuzer, Vice President Medicine Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Our findings show that the antidote’s effects remain consistent following a second administration and also that anticoagulation from dabigatran can be successfully restored 24 hours after idarucizumab is given."

Idarucizumab, a humanized antibody fragment (Fab), was investigated in male and female healthy mid-aged adults (aged 45-64 years), elderly individuals (aged 65-80 years) and those with mild or moderate kidney impairment. The volunteers received dabigatran for 3.5 days before the specific antidote was administered. In some subjects, treatment with dabigatran was restarted 24 hours later. Measurements of the anticoagulant effect of dabigatran as well as its reversal by idarucizumab were taken at baseline, after administration of dabigatran, and after subsequent infusion of idarucizumab or placebo. After two months, the test was repeated in six healthy subjects.¹

The findings from the new study showed:¹

• Administration of idarucizumab resulted in immediate, complete and sustained reversal of dabigatran-induced anticoagulation in both age groups tested and also in subjects with reduced renal function
• Complete reversal was shown right at the end of the five minute infusion of idarucizumab
• Treatment with dabigatran could successfully be restarted 24 hours following administration of idarucizumab and resulted in full re-anticoagulation
• A second administration of idarucizumab, two months after the first one, achieved the same degree of reversal of dabigatran anticoagulation as the first administration
• Idarucizumab was well tolerated– no clinically relevant adverse events were reported
• For the 5g dose of idarucizumab, the reversal effect was consistent independent of age and kidney function. This dose is currently being investigated in the clinical setting³

“These latest data are important because this study included volunteers who were older and who had impaired kidney function – characteristics that are common among patients who require anticoagulation,” said Dr Georg van Husen, Head of Therapeutic Area Cardiovascular, Boehringer Ingelheim. “The growing evidence supports idarucizumab as a highly targeted antidote for dabigatran which can provide immediate, complete and sustained reversal. It would be an additional option for use in clinical situations where patients might benefit from a fast reversal of the anticoagulant effect of Pradaxa^®.”

Boehringer Ingelheim is developing idarucizumab as a highly specific and selective antidote to Pradaxa^® to add a reversal option for physicians. Idarucizumab was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) in June 2014.2 RE-VERSE AD^™, a global patient study, is investigating the reversal of anticoagulation in clinical situations where fast reversal is required. This is the first time that an antidote under development for a novel oral anticoagulant is being investigated in a study in patients, instead of volunteers.³

NOTES TO EDITORS

About Pradaxa^® (dabigatran etexilate)
Clinical experience of Pradaxa^® (dabigatran etexilate) equates to over 3 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.⁴

Currently approved indications for Pradaxa^® are:^5,6​

• 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.⁷ 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.⁸ 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.^7,9

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.

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