Exanta Study

RNS Number:2138P
AstraZeneca PLC
01 September 2003



Phase II study demonstrates promise for ExantaTM (ximelagatran) in reducing
major cardiovascular events following myocardial infarction (MI)


AstraZeneca announced today from the European Society of Cardiology (ESC)
Congress in Vienna, Austria, that data from a phase II dose-guiding study,
ESTEEM*, indicate that oral ExantaTM (ximelagatran), provides significant
additional benefits compared to the current treatment, aspirin, in prevention of
major cardiovascular events in patients following an acute myocardial infarction
(heart attack).  This is the first time an oral DTI has been evaluated in
long-term treatment of patients following heart attack who are at high risk of
arterial thrombotic events, such as further heart attack, stroke or
cardiovascular death.


Results from ESTEEM show that oral Exanta, the first in a new class of oral
direct thrombin inhibitors (oral DTIs), significantly reduces the risk of death,
recurrent heart attack or attacks of severe chest pain from 16.3 per cent to
12.7 per cent (all dose groups combined) during six months treatment in
combination with aspirin, equating to a reduction of risk by 24 per cent (hazard
ratio 0.76; p=0.036) compared with aspirin alone.



AstraZeneca will now focus on incorporating the efficacy and safety results from
ESTEEM alongside those seen in the extensive phase III clinical programme to
date, to establish the overall benefit-risk profile for Exanta in the key
indications under investigation.



ESTEEM, a phase II multi-centre, multinational, placebo-controlled, double-blind
dose-guiding study, involved randomisation of 1883 patients within 14 days of a
heart attack to six months treatment twice daily of either oral Exanta 24, 36,
48 or 60 mg twice daily or placebo.  All patients received 160mg aspirin once
daily.













Overall, a favourable safety profile was seen for Exanta in terms of bleeding
and general adverse events.  There was no significant difference in major
bleeding events between the Exanta and placebo treatment groups (1.8 per cent
Exanta vs 0.9 per cent placebo).  Total bleeding (major and minor) was higher in
the Exanta group, but was comparable to rates seen in recent trials of long-term
warfarin or other agents, and increased in a dose-related manner.



Laboratory blood tests in the study showed an increased incidence of liver
enzyme elevations in patients receiving Exanta, compared with those receiving
placebo, as observed in phase III studies. Elevated liver enzymes were seen in
6.5 per cent of patients at the lowest dose, 24mg, while elevations were seen in
12.2 - 13 per cent of patients at the higher doses.  An incidence of elevated
bilirubin levels above twice the upper limit of normal (> 2XULN) combined with
ALAT above three times the upper limit of normal  (> 3XULN) occurred in 0.6 per
cent of patients in the Exanta group, compared with 0.2 per cent of patients in
the placebo group. As seen in phase III Exanta studies, these ALAT elevations
decreased towards baseline with treatment continuation or discontinuation and
were not typically associated with specific clinical symptoms.  These findings
are under evaluation together with safety results from the full Exanta clinical
study programme in order to establish the overall benefit-risk profile for the
product.



Chronic phase III studies to date have demonstrated a positive benefit-risk
profile for Exanta overall.  The first full presentation of the phase III
SPORTIF III study will take place at the ESC Congress 2003 tomorrow (Tuesday 2
September) and will confirm the potential for Exanta to address a significant
unmet need by preventing strokes in patients with atrial fibrillation (AF).  AF
is a factor behind 15 per cent of all strokes.



Exanta has completed phase III studies in a number of indications and around
30,000 patients have been enrolled in the Exanta clinical trial programme to
date.  Exanta is the first oral anticoagulant to reach late stage clinical
trials since the development of warfarin 60 years ago.    Regulatory submission
for the major indications of stroke prevention in atrial fibrillation and
treatment and long-term prevention of VTE remain on track for late 2003.  The
current worldwide market for antithrombotics is $9.6 billion. The ESTEEM study
is due to be published in The Lancet on 6 September 2003.



1 September 2003

                                     -Ends-







Editors' Notes:

ESTEEM stands for Efficacy and Safety of the oral Thrombin inhibitor
ximelagatran in combination with aspirin, in patiEnts with rEcent Myocardial
damage.   ESTEEM involved 1883 patients at 191 hospitals in 18 countries during
2001-2002. The study compared Exanta in combination with the current standard
treatment, aspirin, to placebo (aspirin alone).



An increase in ALAT > 3 x ULN was seen in 6.5 per cent, 12.9 per cent, 12.2 per
cent and 13.0 per cent of patients in the 24, 36, 48 and 60mg Exanta groups,
respectively, compared with 1.3 per cent in the placebo group.



SPORTIF stands for Stroke Prevention by ORal Thrombin Inhibitor in atrial
Fibrillation, and is the largest-ever stroke prevention study in atrial
fibrillation to date.



The SPORTIF III study is due to be presented in full at the ESC Congress 2003 at
12.00 on Tuesday 2 September 2003.



SPORTIF III   topline data was first presented in a hotline session at the 52nd
Scientific Session of the American College of Cardiology Congress (ACC) in
Chicago on 2 April 2003.  SPORTIF III involves 3407 patients from 259 centres in
23 countries across Europe, Australia and Asia in which 36mg fixed dose oral
Exanta twice daily was compared with dose-adjusted warfarin (INR 2.0-3.0) once
daily.




Media Enquiries:

Steve Brown, [phone]

Investor Enquiries:


Mina Blair-Robinson, [phone]
Jonathan Hunt, [phone]




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