Exanta (ximelagatran) receives first approval

12/23/2003 10:25 AM EST

PublishPublishEXANTA (XIMELAGATRAN) RECEIVES FIRST APPROVAL

First indication for prevention of venous thromboembolic
events in major orthopaedic surgery

AstraZeneca has received its first regulatory approval for
ExantaTM (ximelagatran) in France for the prevention of
venous thromboembolic events in major orthopaedic (hip or
knee replacement) surgery. France is the Reference Member
State for the European Union (EU) Mutual Recognition
Procedure for Exanta. Subject to approval, launches of
Exanta in this first 'proof of principle' indication are
expected to take place later in 2004.

Exanta is the first oral treatment in a new World Health
Organisation class of direct thrombin inhibitors (DTIs) and
is the first new oral anticoagulant approved since the
introduction of warfarin almost 60 years ago. Exanta
benefits from administration as a fixed oral dose, has a
rapid onset and offset of action and shows low potential for
food and drug interactions. Importantly, coagulation
monitoring is also not necessary in treatment with Exanta.

The approval of Exanta for this first indication in France
is based on the METHRO study programme, involving an early
postoperative start of Exanta treatment, with initial
injectable dosing administered at least four hours after the
completion of surgery, followed by oral Exanta 24mg twice
daily for up to 11 days. This approval reflects clinical
practice that is becoming increasingly common in Europe and
allows use in conjunction with spinal anaesthesia with the
oral dosing route enabling treatment to be easily continued
following discharge from hospital. More than half of
patients undergoing major orthopaedic surgery develop VTE in
the absence of preventative anticoagulant treatment, and
while effective treatments are available, no treatment
regimen to date has successfully balanced efficacy and
bleeding risk with oral dosing.

Regulatory submissions for prevention of stroke in atrial
fibrillation and treatment of VTE, have already been filed
in France as part of the EU Mutual Recognition Procedure. In
the US, the Food and Drug Administration (FDA) submissions
for use of Exanta in stroke prevention in patients with
atrial fibrillation and long-term secondary prevention of
VTE have also been filed alongside the orthopaedic surgery
file for use of Exanta in prevention of VTE in total knee
replacement.

"Exanta offers a fundamentally new approach to prevention of
thrombosis, one of the largest causes of morbidity and
mortality in the western world", commented Dr Hamish
Cameron, Vice President, Head of Exanta, AstraZeneca. "We
are very pleased to announce this approval as the first step
in introducing this innovative new anticoagulant to
patients."

Thrombosis leads to the occlusion of blood vessels and
prevents the circulation of blood to the heart (myocardial
infarction) and brain (stroke). When blood clots break away,
they can lead to thromboembolism in the lungs (pulmonary
embolism), limbs (deep vein thrombosis) or within any blood
vessels (venous thrombosis). Each year, nearly four million
people experience thrombosis worldwide and those at greatest
risk include people with atrial fibrillation, those who have
experienced a previous cardiac event such as a myocardial
infarction, and patients following orthopaedic surgery (OS:
total hip or knee replacement surgery). Although existing
treatments are effective, they have many limitations.
Several require subcutaneous or intravenous administration,
whilst current oral treatments are limited by risk of drug
and food interactions, the need for regular coagulation
monitoring and dose titration.

For further information, please see
www.astrazenecapressoffice.com or contact:

NOTES TO EDITORS
· Exanta is a trademark of the AstraZeneca group of
companies.

· * METHRO: MElagatran for THRombin inhibition in
Orthopaedic surgery study that compared injectable low
molecular weight heparinsinitiated the evening before
surgery, with preoperative (METHRO II) or post-operative
(METHRO III) initiation of melagatran (active form) followed
by oral ximelagatran in 4,688 patients undergoing total hip
or knee replacement.

· 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, cardiovascular, neuroscience and
respiratory products. AstraZeneca is listed in the Dow Jones
Sustainability Index (Global and European) as well as the
FTSE4Good Index.

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