New data presented at American Heart Association (AHA) show dabigatran-specific antidote idarucizumab* restores blood clotting mechanism in humans

• This is the first human data presented shown to restore the blood clotting mechanism in healthy volunteers with a NOAC-specific antidote¹
• This sub-study demonstrates that idarucizumab* restores wound site fibrin formation in healthy volunteers taking Pradaxa^®1

BURLINGTON, ON, Nov. 26, 2014 /CNW/ - In a newly-presented sub-study of 35 healthy volunteers, administration of idarucizumab* after initial pre-treatment with Pradaxa^® was shown to restore systemic blood coagulation and re-enable the formation of fibrin, a key component of the blood clotting mechanism.¹ This is the first time that human data has been presented on an antidote to a novel oral anticoagulant (NOAC) that has demonstrated such an effect.¹ The findings were presented during the American Heart Association's Scientific Sessions 2014. The antidote is still under investigation and has not yet been approved for clinical use.

"These data are the first to show idarucizumab* reverses dabigatran-induced inhibition of wound-site fibrin formation, which plays a key role in the blood clotting mechanism," said Dr. Martina Flammer, Vice President, Medical and Drug Regulatory Affairs, Boehringer Ingelheim (Canada) Ltd. "With the development of the dabigatran-specific antidote Boehringer Ingelheim continues to advance anticoagulation therapy, demonstrating our commitment to research and scientific innovation."

In this sub-study, fibrin formation was assessed after a small scratch, similar to a paper cut, was made after administration of Pradaxa^® and after subsequent administration of idarucizumab* or placebo.

The results showed that dabigatran almost completely inhibited the production of fibrinopeptide A (FPA), the marker of fibrin formation at the wound site, and that idarucizumab* restored FPA production:¹

• At baseline, before the volunteers took Pradaxa^®, the mean level of FPA was 3981 ± 1842 ng/ml.
• On day three, 2.5 hours after the volunteers took Pradaxa^®; the level of FPA was 208 ± 30 ng/mL, an approximate 95 per cent decrease compared to baseline.
• On day four, 2.5 hours after the volunteers took Pradaxa^® and 30 minutes after they were infused with 1 g, 2 g or 4 g of idarucizumab*, FPA levels were 24 per cent, 45 per cent and 95 per cent, respectively, of the average baseline level.

The restored fibrin production at the wound site after idarucizumab* dosing with 2 g or 4 g also correlated with reversal of the dabigatran-anticoagulation activity in circulating blood.

In summary, the results showed that Pradaxa^® almost completely inhibited the fibrin formation at the wound site, and that idarucizumab* restored fibrin formation. Pradaxa^® and idarucizumab* were well tolerated.¹

Translation into reversal of bleeding in patients requires further clinical investigations, which are currently ongoing. RE-VERSE AD™ a global patient study, has been underway since May 2014 to investigate the antidote in the clinical setting in patients taking Pradaxa^® who have uncontrolled bleeding or require emergency procedures. The study will be open to eligible patients in more than 35 countries and was recently initiated in Canada. This is the first time that an antidote under development for a novel oral anticoagulant is investigated in a study in patients, instead of healthy volunteers.²

NOTES TO THE EDITORS

About Pradaxa^® (dabigatran etexilate)
Pradaxa^® is a novel, reversible oral direct thrombin inhibitor.³ It provides its anticoagulant effect by selectively blocking the activity of thrombin, the central enzyme in clot formation.³

Pradaxa^® was first approved for the prevention of venous thromboembolic events (VTE) in patients who have undergone elective total hip replacement or total knee replacement surgery.³ It was then approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF), in whom anticoagulation is appropriate.³ Pradaxa^® was most recently  approved for the treatment of venous thromboembolism events (deep vein thrombosis [DVT], pulmonary embolism [PE]) and prevention of recurrent DVT and PE.³ To date, over 130,000 Canadians with AF have received Pradaxa^® for stroke prevention.⁴

Pradaxa^® has been in the market for more than five years and is approved in over 100 countries.⁴ 

The efficacy and safety profile of Pradaxa^® in its licensed indications is well documented in an extensive clinical trial programme.^5-12 In addition, the favourable benefit-risk profile of Pradaxa^® is supported by safety assessments from regulatory authorities including the European Medicines Agency and the U.S. Food and Drug Administration (FDA).^13-15 Most recently in May 2014, in one of the largest real-world analyses of its kind, the FDA once again re-affirmed the favourable benefit/risk profile of Pradaxa^® when it issued results from this study, including more than 134,000 patients.¹⁶

As the first novel oral anticoagulant to market, clinical experience with Pradaxa^® continues to grow and equates to over three million patient-years in all licensed indications to date.⁴ Pradaxa^® has the longest clinical trial experience in DVT and PE patients of any novel oral anticoagulant (NOAC).^{5, 17-22} DVT and PE patients can start taking Pradaxa^® in a simple fixed dose regimen after initial treatment with an injectable anticoagulant such as low-molecular-weight heparin (LMWH).³

For dosing, side effects, warnings and precautions, please refer to the Pradaxa^® Product Monograph:  http://www.boehringer-ingelheim.ca/content/dam/internet/opu/ca_EN/documents/humanhealth/product_monograph/PradaxaPMEN.pdf

About Boehringer Ingelheim (Canada) Ltd.
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.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs more than 550 people across Canada.

______________________________
* Idarucizumab is an investigational compound. Its safety and efficacy has not yet been fully established and it is currently not authorized for sale in Canada.

	References
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2.	Glund 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.
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SOURCE: Boehringer Ingelheim (Canada) Ltd.

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