Exanta
AstraZeneca PLC
02 April 2003
NEW STUDY DEMONSTRATES THE POTENTIAL OF EXANTATM (ximelagatran) FOR PREVENTION
OF STROKE IN ATRIAL FIBRILLATION
AstraZeneca today announced results from the first phase III stroke prevention
data for ExantaTM (ximelagatran), the first of a new class of oral direct
thrombin inhibitors (Oral DTI), presented at the 52nd Scientific Session of the
American College of Cardiology (ACC), Chicago. The results show that fixed dose
twice daily 36mg oral Exanta compares favourably with dose-adjusted warfarin in
preventing stroke and systemic embolic events (SEE) in patients with atrial
fibrillation (AF), meeting the study's primary efficacy endpoint.
SPORTIF III*, a multi-national, randomised, open-label, parallel-group study
with blinded event assessment, was designed as a non-inferiority** study to
compare oral Exanta with the current standard treatment, dose-adjusted warfarin.
While the study was not aimed at demonstrating superiority, the incidence of
stroke and SEE 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 relative risk reduction (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).
These promising efficacy results need to be considered alongside the safety
profile for Exanta emerging from this study and from other ongoing clinical
trials, which will define its overall benefit-risk profile. In SPORTIF III, the
incidence of liver enzyme (ALT) elevations was 6.5% for Exanta and mostly
occurred within the first six months of treatment. These elevations were
associated with no specific clinical symptoms and decreased with treatment
continuation or discontinuation. With regard to bleeding and recognising that
Exanta was used in a fixed dose regimen without coagulation monitoring, 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.
'Today's results confirm the potential of Exanta in stroke prevention for AF
patients and highlight the important practical advantages that this unique
first-in-class treatment holds over the traditional, standard treatment,' says
Dr. Hamish Cameron, Vice President, Head of Exanta, AstraZeneca. 'These data,
together with the results of SPORTIF V and other important studies, will form
the basis for the FDA and EU submissions for Exanta in this indication, which
are on track for the fourth quarter this year.'
SPORTIF is the largest clinical study programme ever undertaken in the
prevention of stroke in atrial fibrillation. 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.
Exanta is currently under review in Europe for the prevention of venous
thromboembolism (VTE) following elective hip or knee replacement surgery and
will be submitted for regulatory approval in the US for the same indication in
Q4 2003. A regulatory submission for the treatment of VTE is also scheduled to
be submitted in Europe in the fourth quarter of this year, following the outcome
of studies in this indication.
Stroke is the third leading cause of death in adults worldwide, with five
million fatal events per year. Atrial fibrillation has been found to increase
the risk of stroke fivefold, yet less than half of eligible patients receive
effective treatment. This unmet need may be attributed to the limitations of
the current standard treatment, warfarin, which requires regular coagulation
monitoring, dose titration and has several food and drug interactions. The
current worldwide market for antithrombotics is $9.6 billion.
Exanta is the first of a new class of oral anticoagulants called oral DTIs. The
drug 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.
Exanta is a trademark of the AstraZeneca group of companies.
- Ends -
April 2, 2003
Media Inquiries:
Steve Brown, +44 (0) 207 304 5033
Emily Denney, +44 (0) 207 304 5034
Investor Inquiries:
Mina Blair-Robinson, +44 (0) 207 304 5084
Jonathan Hunt, +44 (0) 207 304 5087
Editors' Notes:
*SPORTIF : Stroke Prevention by ORal Thrombin Inhibitor in atrial Fibrillation.
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. Patients were treated for an average of 17 months in SPORTIF III.
** 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.
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
This information is provided by RNS
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