SPORTIF III, a multi-national, randomised, open-label, parallel-group study with blinded event assessment, was designed as a non-inferiority** study to compare Exanta with the current standard treatment, dose-adjusted warfarin. The primary efficacy endpoint was met, showing that fixed dose twice daily 36mg oral Exanta compares favourably with dose-adjusted warfarin, in preventing stroke and systemic embolic events (SEE) in atrial fibrillation. While the study was not aimed at demonstrating superiority, the incidence of stroke and systemic embolic events seen for Exanta compared with a well-controlled warfarin treatment (average study INR 2.5) was numerically lower (40 Exanta vs 56 warfarin) in the whole population (ITT - including those who stopped treatment). Furthermore, a statistically significant RRR of 41% (p=0.018) was demonstrated for Exanta compared with well-controlled warfarin in patients who remained on treatment for the duration of the study (OT population).
"The results of the SPORTIF III study suggest that Exanta can offer great improvement in preventing stroke in patients with atrial fibrillation. As a physician, this is a very exciting breakthrough, as we may be able to offer our patients a much-needed alternative to warfarin treatment and its associated complications, while knowing that we are not compromising on efficacy" comments Professor Bertil Olsson, SPORTIF III Key Investigator and Professor of Cardiology, University Hospital, Lund, Sweden.
Safety data from SPORTIF III, in which patients were treated for an average of 17 months, also support the emerging benefit-risk profile for Exanta. The combined rate of major and minor bleeding events was found to be significantly lower for Exanta than warfarin (475 vs 554 events; p=0.007) and there was no significant difference in all cause mortality between the Exanta and warfarin groups, despite Exanta's lack of coagulation monitoring and fixed dose regimen.
In the SPORTIF III trial, the incidence of liver enzyme (ALT) elevations was 6.5% for Exanta and mostly occurred within the first six months of treatment. This remains in the range detected in other clinical studies to date and, also consistent with previous clinical trials, these elevations were associated with no specific clinical symptoms and decreased with treatment continuation or discontinuation. The safety results from SPORTIF III will be evaluated together with results from previous and future studies in the Exanta clinical study programme, to form the overall benefit-risk profile for the product.
Stroke is the third leading cause of death in adults worldwide, with five million fatal events per year 1,2. Atrial fibrillation has been found to increase the risk of stroke fivefold3.
"Only one in two patients with permanent atrial fibrillation currently receive appropriate anticoagulation treatment for stroke prevention," adds Professor Olsson. "People receiving warfarin therapy have to go to their doctor or to the lab, at least once a month and sometimes even more frequently, to have their treatment monitored. Treatment with Exanta is less complex as there is no need for coagulation monitoring, dose titration, dietary restrictions and it is not associated with serious side effects. These results will hopefully mean that many more patients with atrial fibrillation in the future may benefit from a greater chance of avoiding strokes."
The SPORTIF III study will be complemented later this year by the North American SPORTIF V study, which only differs to SPORTIF III in that it is a double-blind study. These combined data aim to form the basis for the FDA and EU approval application for EXANTA in this indication, which is on track for the fourth quarter of this year.
"We are very pleased to see the potential for Exanta in stroke prevention among patients with atrial fibrillation demonstrated in the SPORTIF III study. This highlights the important practical advantages that this unique first-in-class treatment holds over a traditional treatment option, and reinforces our belief in the unique impact that Exanta could have on anticoagulant treatment", says Hamish Cameron, Vice President, Head of Exanta, AstraZeneca.
Exanta is currently under phase III investigation and is the first oral anticoagulant to reach late clinical development in more than 50 years – since the development of warfarin.
For further information please see www.astrazenecapressoffice.com or contact:
Ross Wilkie
Ketchum – media information
mobile: 44-773-434-3164
office: 44-207-611-3603
email: ross.wilkie@ketchum.com
Julie Saunders
AstraZeneca – media information
mobile: 46-708-46-76-33
office: 46-317-006-4865
email: julie.saunders@astrazeneca.com
Exanta is a trademark of the AstraZeneca group of companies.
NOTES TO EDITORS
*SPORTIF : Stroke Prevention by ORal Thrombin Inhibitor in atrial Fibrillation, is the largest-ever stroke prevention study in atrial fibrillation to date SPORTIF III involves 3407 patients from 259 centres in 23 countries across Europe, Australia and Asia. 36mg fixed dose oral Exanta twice daily was compared with dose-adjusted warfarin (INR 2.0-3.0) once daily. Patients in the study had Non-valvular atrial fibrillation (AF) and at least one additional risk factor for stroke, which included: previous cerebral ischaemic attack; previous systemic embolism; hypertension; left ventricular dysfunction; age 3 75 years; age 3 65 years and coronary artery disease; age 3 65 years and diabetes mellitus.
** The rationale for 'non-inferiority' studies:
As many highly effective treatments are now available in various therapeutic areas, placebo-controlled trials are often now considered unethical. Therefore, the concept of non-inferiority testing is now increasingly common where objective of these studies is to demonstrate that a treatment is 'not inferior to' or 'as effective as' a gold standard treatment. This can then enable treatments to be differentiated in terms of their respective additional advantages to the patient and physician, such as predictability and convenience.
Additional AstraZeneca data to be presented at ACC:
- CRESTOR MERCURY I Study, Sunday 30 March, 09:00-11:00, McCormick Place Convention Center, Hall A: Herbert Schuster. Effects of Switching to Rosuvastatin From Atorvastatin or Other Statins on Achievement of International Low-Density Lipoprotein Cholesterol Goals: MERCURY I Trial. 52nd Annual Scientific Session of the American College of Cardiology, Chicago, USA, March 2003.
- CRESTOR STELLAR Study, Wednesday 2 April, 08:45-09:00 McCormick Place Convention Center, Room S101: Peter H. Jones. Statin Therapies for Elevated Lipid Levels Compared Across Dose Ranges to Rosuvastatin: Low-Density Lipoprotein Cholesterol and High-Density Lipoprotein Cholesterol Results. 52nd Annual Scientific Session of the American College of Cardiology, Chicago, USA, April 2003.
Abstracts will be available online at www.acc.org and once these data have been presented media materials will be available on www.astrazenecapressoffice.com
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the top five pharmaceutical companies in the world with healthcare sales of over $17.8 billion and leading positions in sales of gastrointestinal, oncology, anaesthesia (including pain management), cardiovascular, central nervous system (CNS) and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global and European) as well as the FTSE4Good Index.
References
1. The European Stroke Initiative: Recommendations for stroke management
http://www.eusi-stroke.com/l3_pdf/Recommendations2002.pdf
2. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet 2001;358:1033-1041
3. Lip GYH, Hart RG, Conway DSG. Antithrombotic therapy for atrial fibrillation. BMJ 2002;325:1022-1025