Boehringer Ingelheim announces first positive health technology assessments for novel oral anticoagulant Pradaxa® (dabigatran etexilate)

Ingelheim/Germany, 9 June 2008 - The Scottish Medicines Consortium (SMC) has accepted Pradaxa^®(dabigatran etexilate) for routine use within the National Health Service (NHS) of Scotland for its currently licensed indication: the prevention of venous thromboembolic events in adults who have undergone total hip or knee replacement surgery. The European Commission granted marketing authorisation for Pradaxa^® in all 27 EU member states in March 2008.

Also the Danish Institute for Rational Pharmacotherapy (IRF) which belongs to the Danish Medicines Agency has endorsed Pradaxa^® as a good alternative to low molecular weight heparins (LMWH) both with respect to efficacy and ease of use.

These decisions on Pradaxa^® are the first by European health technology assessment bodies and their positive outcomes are likely to be viewed favourably by decision makers considering the implementation and reimbursement of Pradaxa^® across the EU as they indicate Pradaxa^® has fulfilled all clinical and cost-effectiveness criteria necessary for use within the NHS in Scotland and clinical criteria necessary for use in Denmark.

Data from the phase III RE-NOVATE™ and RE-MODEL™ studies showed oral, once daily administration of both 150 and 220 mg Pradaxa^® was as effective and safe as injectable enoxaparin (40 mg) inpreventing venous thromboembolism (VTE) and all cause mortality following total hip and total knee replacement surgery.^1,2 In contrast to low molecular weight heparins (LMWH), which require subcutaneous injection, Pradaxa^® is administered as a fixed, oral dose making it significantly easier to administer both in the hospital setting and, more importantly, in the home setting after discharge. Unlike both LMWH and warfar in, Pradaxa^® does not require monitoring.

Patients undergoing hip and knee replacement surgery are at particularly high risk of developing VTE.³ Without thromboprophylaxis, up to 60 percent of orthopaedic surgery patients have been shown to develop DVT (deep vein thrombosis; including asymptomatic thrombi), and 0.2-10 percent are at risk of apotentially fatal PE (pulmonary embolism) according to previous studies.³ It is estimated that 543,454 deaths in Europe per year are VTE-related, more than double the number from breast cancer, prostate cancer, HIV/AIDS and road traffic accidents combined.⁴

Professor Simon Frostick, Professor of Orthopaedics at the University of Liverpool, UK said:
“We know that thromboprophylaxis after orthopaedic surgery is crucialto protect patients from potentially life-threatening thrombi. Now, with Pradaxa^®as a new therapeutic option, we have an effective oral, once-daily anticoagulant with a good efficacy and safety profile to facilitate convenient thrombo prophylaxis both in and out of hospital.”

The registered charity Anti Coagulation Europe (ACE) which works to prevent thrombosis and provide information for patients also welcomed the decision. Executive Director Eve Knight said:
“This could mean saving lives. Pradaxa^® is potentially a huge benefit for patients. One of the reasons why patients are not given thromboprophylaxis is that they have to have heparin which has to be injected. Following hospital discharge, many patients have to learn to self-inject which may result in inadequate treatment duration due to poor compliance. Pradaxa^® is so much more convenient; just two capsules once a day.”

Pradaxa^® has a rapid onset and offset of action and a predictable anticoagulation effect. It prevents thrombus formation by specifically and selectively inhibiting thrombin, the central and essential enzyme in the coagulation cascade that enables conversion of fibrinogen into fibrin. In contrast to warfar in, Pradaxa^® exhibits no drug-food interactions and has a low potential for drug-drug interactions.^5,6
Boehringer Ingelheim continues to evaluate the efficacy and safety of Pradaxa^® in a range of thromboembolic disease conditions. RE-VOLUTION™ is anextensive clinical trial programme involving more than 38,000 patients worldwide. Recent progress includes the announcement in January 2008 of the completion of enrolment of 18,114 patients in RE-LY™, the largeststroke prevention a trial fibrillation outcomes trial to date. Other ongoing studies are evaluating the efficacy and safety of Pradaxa^® in the treatment of acute VTE, the secondary prevention of VTE and prevention of cardiac events in patients with acute coronary syndrome.

Notes to Editors
The wording of the SMC advice following a full submission is:

“dabigatran etexilate (Pradaxa) is accepted for use within NHS Scotland for the primary prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery.

“In two large phase III studies, in patients undergoing either total knee or total hip replacement surgery, dabigatran was non-inferior tolow molecular weight heparin in the incidence of VTE and all cause mortality with patients having a similar incidence of major bleeding events. The two drugs have similar costs per dose but dabigatran has lower administration costs and is an oral therapy. This may facilitate longer duration of thromboprophylaxis; however the risks and benefits of this longer treatment duration need to be considered on acase-by-case basis.”⁷

Please be advised
This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of 10.9 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.