CHMP grants positive opinion for idarucizumab, the specific reversal agent for dabigatran etexilate (Pradaxa)

  • First specific reversal agent for a non-vitamin K antagonist oral anticoagulant (NOAC) to gain CHMP positive opinion1
  • Positive opinion is based on clinical trial results which showed that idarucizumab reverses the anticoagulant effect of dabigatran within minutes2-4

Ingelheim, Germany, 25 September 2015 - Today, the Committee for Medicinal Products for Human use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending European approval of idarucizumab (to be marketed as Praxbind®).1 Idarucizumab is intended for use in adult patients treated with Pradaxa® (dabigatran etexilate) when rapid reversal of its anticoagulant effects is required for emergency surgery / urgent procedures or in life-threatening or uncontrolled bleeding.1

"The CHMP positive opinion in favour of idarucizumab approval is an important recommendation in the field of anticoagulation care," said Professor Fausto J. Pinto, University of Lisbon, Portugal, and President of the European Society of Cardiology. "The introduction of non-vitamin K antagonist oral anticoagulants, or NOACs, already marked a significant advancement in anticoagulation care. The approval of specific reversal agents to stop their anticoagulant effect immediately when needed will be the next advancement."

"This will be the icing on the cake for treating our stroke patients with anticoagulants like dabigatran: in an emergency we will be able to switch off their treatment almost instantly, and safely. This will make treatment choices much easier for both doctor and patient," stated Professor Kennedy R. Lees, University of Glasgow, UK, and President of the European Stroke Organisation.

The CHMP positive opinion was based on data from healthy volunteers, as well as results from an interim analysis of the RE-VERSE AD™ trial.2-5 In the studies, the reversal effects of idarucizumab were evident immediately, within minutes after administration of 5 grams of idarucizumab.2-4 Reversal was complete and sustained in almost all patients.2-5 No serious adverse events considered causally related to idarucizumab were identified.2-5 Additionally, no pro-coagulant effect was observed after the administration of idarucizumab.2,5

"Our scientists have worked intensively on idarucizumab for years, so we are now very excited about this recommendation for European approval", said Professor Jörg Kreuzer, Vice President Medicine, Therapeutic Area Cardiovascular, Boehringer Ingelheim. "I am convinced that the availability of idarucizumab will give physicians and patients added assurance in choosing dabigatran as the first ever NOAC with a specific reversal agent."

Idarucizumab is currently being reviewed for approval by regulatory authorities worldwide6, including the U.S. FDA7. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.6

NOTESTO THE EDITORS

About the idarucizumab Clinical Trial Programme
Idarucizumab was discovered and developed by Boehringer Ingelheim scientists.6 The research programme was initiated in 20096, before dabigatran (Pradaxa®) was launched in the U.S. in 20108. The company completed three phase I trials of idarucizumab in human volunteers and is continuing to evaluate idarucizumab in RE-VERSE AD™ (NCT 02104947, EudraCT 2013‐004813‐41), a phase III global study that includes patients taking Pradaxa® who require emergency procedures or have uncontrolled bleeding.2-5 The study is the first of its kind in patients, and has been underway since May 2014, enrolling patients in more than 35 countries.9 The RE-VERSE AD™ global phase III patient study is ongoing to capture further data on the efficacy and safety profile of idarucizumab.

About idarucizumab
Idarucizumab is a humanized antibody fragment, or Fab, designed as a specific reversal agent to dabigatran.10 Idarucizumab binds specifically to dabigatran molecules only, neutralising their anticoagulant effect without interfering with the coagulation cascade.10

Idarucizumab is recommended for approval for use in adult patients treated with Pradaxa® (dabigatran etexilate) when rapid reversal of its anticoagulant effects is required for emergency surgery / urgent procedures or in life-threatening or uncontrolled bleeding.1

Regulatory reviews and submissions in other countries are ongoing.6 Idarucizumab is the only specific reversal agent for a NOAC currently in regulatory review.6 Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.6

About dabigatran etexilate (Pradaxa®)
Clinical experience of dabigatran equates to over 4.6 million patient-years in all licensed indications worldwide.6 Dabigatran has been in the market for more than 6 years and is approved in over 100 countries.6

Currently approved indications for dabigatran are:8,11

  • 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.11,12 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.13 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.12,14

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. Committee for Medicinal Products for Human Use (CHMP). Minutes from 21-24 September 2015 meeting. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003986/WC500194147.pdf
2. Glund S, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015;386:680-690.
3. Glund S. et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects. Oral presentation on 8 December 2014 at The 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA. Blood 2014; 124: Abstract 344.
4. Pollack C. V., et al. Idarucizumab for Dabigatran Reversal. NEJM. 2015;373:511-520.
5. Glund S, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113:943-951.
6. Boehringer Ingelheim data on file.
7. Boehringer Ingelheim Press Release - 03 March 2015. Boehringer Ingelheim submits applications for approval of idarucizumab, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2015/03_march_2015_dabigatranetexilate.html. Last accessed September 2015.
8. Pradaxa® US Prescribing Information, 2015.
9. Boehringer Ingelheim Press Release - 22 May 2015. 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 September 2015.
10. 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):198-20.
11. Pradaxa® European Summary of Product Characteristics, 2015.
12. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-95.
13. Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028-40.
14. 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.

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