Positive UK health technology appraisal for novel oral anticoagulant Pradaxa® (dabigatran etexilate)

Ingelheim/Germany, 24 September 2008 – The UK’s National Institute for Health and Clinical Excellence (NICE) has recommended Pradaxa® (dabigatran etexilate) as an option, within its marketing authorisation, for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip or elective total knee replacement surgery throughout the National Health Service (NHS) of England and Wales.¹

After a single technology appraisal, NICE stated that oral once daily Pradaxa® was likely to be of equivalent clinical and cost effectiveness to the standard care options for the prevention of venous thromboembolism (VTE) which are generally administered via injection and/or require monitoring.¹ NICE highlighted that oral administration of Pradaxa®, without the need for monitoring, would reduce administration costs and may support adherence to treatment.¹ This NICE recommendation of Pradaxa® provides widely recognised endorsement for the product’s clinical efficacy, safety and cost effectiveness.

Professor Ajay Kakkar MD, Professor of Surgical Sciences at Barts and the London School of Medicine, commented:

“Venous thromboembolism remains an important clinical challenge. Today’s recommendation by NICE for the novel orally active anticoagulant dabigatran provides an important extension to our armamentarium for preventing potentially fatal blood clots after total hip and knee replacement surgery, further facilitating best practice in terms of out of hospital prevention.”

This positive assessment marks a key milestone for Pradaxa®. Rapid progress has already been made as Health Technology Appraisal bodies in Scotland (Scottish Medicines Consortium), Denmark (Danish Medicines Agency), the Netherlands (The Health Care Insurance Board) and Greece have favourably appraised Pradaxa®’s clinical and cost effectiveness. The regulatory approval of Pradaxa® by the European Medicines Agency (EMEA) was obtained in March 2008^2,3 and marketing authorisations were also received from Canada, Brazil, New Zealand and Argentina amongst others. To date, Pradaxa® has been launched across a total of eleven countries.

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 In the UK alone, VTE is estimated to cost 640 million GBP (950 million euros) every year to manage, yet 60 to 80 per cent of these costs could be saved through preventative measures including anticoagulation.^4,5

The charity AntiCoagulation Europe welcomed NICE’s recommendation. Chief Executive, Eve Knight, said:

^{“We are delighted with today’s NICE announcement. It is appalling that patients are still developing and dying from VTE, which could very often be prevented by risk assessing every patient on admission to hospital and giving preventative treatment where needed. Pradaxa, a once daily oral therapy for use in post orthopaedic surgery, will enable clinicians and patients to make decisions on choice of treatment appropriate to their clinical needs.”}

Data from the phase III RE-NOVATETM and RE-MODELTM studies showed oral, once daily administration of both 150 and 220 mg Pradaxa® was as effective and safe as injectable enoxaparin (40 mg) in preventing VTE and all cause mortality following total hip and total knee replacement surgery.^6,7

Dr Andreas Barner, Vice Chairman of the Board of Boehringer Ingelheim and responsible for Research, Development and Medicine said:

“Today’s announcement from NICE represents an important milestone for Pradaxa. We are pleased that since the EMEA approval in March Pradaxa has progressed smoothly through key EU Health Technology Appraisals. Our ongoing extensive RE-VOLUTIONTM clinical trial programme is investigating Pradaxa across several further therapeutic areas.”

Pradaxa® is an oral direct thrombin inhibitor with a rapid onset and offset of action and a predictable anticoagulation effect without the need for coagulation monitoring.^8,9 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.^9-1 In contrast to warfarin, Pradaxa® exhibits no drug-food interactions and has a low potential for drug-drug interactions.^10,12

Boehringer Ingelheim continues to evaluate the efficacy and safety of Pradaxa® within the global RE-VOLUTION™ clinical trial programme which involves over 38,000 patients. Pradaxa®’s efficacy and safety is being assessed for:Stroke prevention in atrial fibrillation (SPAF) in the RE-LY™ trial – the largest SPAF trial to date Enrollment of a total of 18,113 patients for the RE-LY™ trial was completed in December 2007.

Results are expected in 2009
Treatment of acute VTE - results expected in 2009
Secondary prevention of VTE
Prevention of cardiac events in patients with acute coronary syndrome

Notes to Editors
Wording of Today’s NICE announcement
Dabigatran etexilate, within its marketing authorisation, is recommended as an option for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip replacement surgery or elective total knee replacement surgery.

The Committee acknowledged that oral administration of dabigatran etexilate, without the need for monitoring, would reduce administration costs and may support adherence to treatment. The Committee therefore concluded that dabigatran etexilate should be recommended as an option in the circumstances in which LMWH (or fondaparinux as an alternative) may be offered.

Recommended Dosing of Pradaxa® for VTE Prevention
The standard recommended dosage of Pradaxa® in VTE prevention is a fixed oral dose of 220 mg given once daily.¹² A single capsule of 110 mg (half-dose) is administered orally between 1 and 4 hours following surgery, continuing with 2 capsules once daily thereafter for a total of 10 days in total knee replacement patients and 28-35 days in total hip replacement patients.¹² A second approved dosage of 150 mg taken as two capsules of 75 mg is recommended for specific patient populations, including patients over 75 years of age and those with moderate renal impairment.¹²

Please be advised
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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.