Favorable Safety Profile of Pradaxa^® (dabigatran etexilate) Confirmed in Large Prospective Real-world Analysis

Complete Phase II results from the prospective GLORIA^TM-AF registry in dabigatran patients presented as a late-breaker at the EHRA 2018, the annual congress of the European Heart Rhythm Association (EHRA)¹

Low rates of major bleeding and stroke observed for dabigatran patients¹

Long-term safety data^1,2 highly consistent with other available real-world evidence and randomised clinical trials

INGELHEIM, GERMANY – New data from one of the largest prospective ongoing global studies examining the use of oral antithrombotics for stroke prevention in atrial fibrillation (AF) in clinical practice, GLORIA^TM-AF, were presented at the EHRA 2018, the annual congress of the European Heart Rhythm Association (EHRA).^1,2 The registry examined two-year safety and effectiveness outcomes of nearly 5,000 AF patients treated with dabigatran (marketed as Pradaxa^®). Results of the completed Phase II of GLORIA^TM-AF,¹ presented during the ‘Late-breaking science – Registries’ session, showed low rates of major bleeding (0.97%) and stroke (0.65%). These findings confirm the sustained safety and effectiveness of dabigatran and are highly consistent with the long-term safety profile observed in other real-world evidence, as well as in randomised clinical trials.

“Long-term, ‘real-world’ data are important to cardiologists as they help build a bigger picture of how an antithrombotic medication works in daily clinical practice,” commented Gregory Y H Lip, MD, Co-Chair of the GLORIA^TM-AF Steering Committee. “The results from the second phase of GLORIA^TM-AF underline the safety and effectiveness of dabigatran, which is reassuring for physicians treating patients with atrial fibrillation.”

In an additional analysis from GLORIA^TM-AF² the safety of uninterrupted dabigatran for patients undergoing cardiovascular (CV) interventions was evaluated. The rates of major bleeding and stroke/ systemic embolism were very low, i.e. one major bleed and one systemic embolic event occurred in 412 CV interventions that were performed with uninterrupted dabigatran.

“From the first clinical trials such as RE-LY^® and RELY-ABLE^®, through to numerous real-world studies, both supported by and independent from Boehringer Ingelheim, we get an absolute, consistent picture of the favorable safety of dabigatran,” commented Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. “Recent clinical trials in specific settings like RE-CIRCUIT^TM,³ with dabigatran in AF patients undergoing cardio ablation, again demonstrated the superior safety of Pradaxa^® compared to standard-of-care. The prospective, long-term data for dabigatran from GLORIA^TM-AF now add one further piece to complete this picture with profound real-world evidence.”

AF is the most common cardiac rhythm disorder worldwide, with numbers expected to rise in the coming years.⁴ Overall, people diagnosed with AF have a five-fold increased risk of stroke,⁵ which occurs when a blood clot blocks a vessel in the brain. Each year three million patients suffer AF-related strokes.^6,7

NOTES TO EDITORS

About GLORIA^™-AF

(Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation)

GLORIA^™-AF is one of the largest worldwide registry programs to investigate the long-term use of oral antithrombotic therapies in the prevention of non-valvular AF-related strokes in a routine clinical setting. The Registry examines physicians’ prescribing behaviors in treating AF, as well as the factors behind their prescribing decisions. In addition, GLORIA^TM-AF Phase II, which has recently completed, provides safety and effectiveness data from dabigatran during 2 years of follow-up. Phase III, which is currently ongoing, follows patients independent of antithrombotic therapy for three years to evaluate the safety and effectiveness of oral anticoagulants (OACs). GLORIA^TM-AF is currently the only study with the objective to provide long-term prospective comparative real-world outcomes of OACs for AF during its third Phase.^8,9

The Registry will enroll up to 56,000 patients newly diagnosed with AF at risk of stroke from up to 2,200 sites in nearly 50 countries.⁸ So far more than 38,000 patients have been included.

For more information please visit: https://www.gloria-af.com/public/about.html (link is external)

About Pradaxa^® (dabigatran etexilate)

Clinical experience of Pradaxa^® equates to over 7.9 million patient-years in all licensed indications worldwide. Pradaxa^® has been in the market for more than eight years and is approved in over 100 countries.¹⁰

Currently approved indications for Pradaxa^® are: ^11,12

• 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 deep vein thrombosis (DVT) and pulmonary embolism (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.^13–15 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.¹⁵ 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

Pradaxa^® is the only non-vitamin K antagonist oral anticoagulant with an approved reversal agent. Praxbind^® is approved in the European Union and United States 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.^16,17

About Boehringer Ingelheim

Innovative medicines for people and animals have for more than 130 years been what the research-driven pharmaceutical company Boehringer Ingelheim stands for. Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies and to this day remains family-owned. Day by day, some 50,000 employees create value through innovation for the three business areas human pharmaceuticals, animal health and biopharmaceutical contract manufacturing. In 2016, Boehringer Ingelheim achieved net sales of around 15.9 billion euros. With more than three billion euros, R&D expenditure corresponds to 19.6 percent of net sales.

Social responsibility comes naturally to Boehringer Ingelheim. That is why the company is involved in social projects such as the “Making More Health” initiative. Boehringer Ingelheim also actively promotes workforce diversity and benefits from its employees’ different experiences and skills. Furthermore, the focus is on environmental protection and sustainability in everything the company does.

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.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. Lip GYH. et al. Two-year safety and effectiveness of dabigatran in patients with atrial fibrillation: Final Phase II results of the GLORIA-AF Registry Program. (Abstract 1055) Presented at EHRA 2018, the annual congress of the European Heart Rhythm Association (EHRA), March 20, 2018.
2. Lip GYH. et al. Safety of uninterrupted dabigatran for cardiovascular interventions in the GLORIA-AF Registry Program. (Abstract 200) Presented at EHRA 2018, the annual congress of the European Heart Rhythm Association (EHRA), March 18, 2018.
3. Calkins H. et al. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation. NEJM. 2017. DOI: 10.1056/NEJMoa1701005.
4. Lloyd-Jones. DM. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042-46.
5. Camm. AJ. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33(21):2719-47.
6. Kirchhof. P. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-2962.
7. Atlas of Heart Disease and Stroke, World Health Organization, September 2004.
8. Huisman MV. et al. Design and rationale of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation: A global registry program on long-term oral antithrombotic treatment in patients with atrial fibrillation. Am Heart J. 2014;167:329–34.
9. GLORIA-AF Registry website: Registry Design. https://www.gloria-af.com/public/about-regDesign.html Last accessed March 2018.
10. Boehringer Ingelheim, data on file.
11. Pradaxa^® US Prescribing Information, 2015.
12. Pradaxa^® European Summary of Product Characteristics, 2016.
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.
16. Praxbind^® European Summary of Product Characteristics, 2016.
17. Praxbind^® US Prescribing Information, 2015.