NEW AZD6140 PHASE IIb DATA PRESENTED AT AMERICAN HEART ASSOCIATION

AZD6140 is the first oral reversible ADP receptor antagonist that selectively blocks the P2Y₁₂ receptor, a key target receptor for ADP on platelets, and is being developed for the prevention of thrombotic events, such as heart attack and stroke, in patients with acute coronary syndrome (ACS).

Results showed that the overall incidence of total bleeding events (major plus minor) was similar amongst patients taking AZD6140 and clopidogrel at 10.2% (AZD6140 90 mg group), 10.2% (AZD6140 180 mg group) versus 9.2% (clopidogrel 75 mg group). Within these figures, those considered as major bleeds totalled 7.8% (AZD6140 90 mg group), 6.2% (AZD6140 180 mg group) versus 8.0% (clopidogrel 75 mg group).

"The hypothesis is that a new antiplatelet therapy that can offer a higher level of inhibition of platelet aggregation could have an even greater clinical benefit. This would need to be tested in a large clinical trial, but the data today are an important step: precisely because there has been concern in the past that with a higher level of inhibition one might expect to see an increased risk of bleeding. In the current study, this was not the case with AZD6140," said Dr. Christopher Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, and DISPERSE2 lead investigator.

Both doses of AZD6140 were well tolerated over the 12-week study. Discontinuations due to adverse events were low and comparable across all treatment groups with 6% of patients in the AZD6140 90 mg group; 7% of patients in the AZD6140 180 mg group and 6% in the clopidogrel 75 mg group. No difference was observed between the groups for CV death, stroke or recurrent ischaemia endpoints. A non-significant trend was observed suggesting decreased myocardial infarction (MI) events in the AZD6140 groups.

This is the second AZD6140 study in patients presented at a major medical meeting. The first study, DISPERSE, which compared the ability of AZD6140 to inhibit platelet aggregation to clopidogrel, was presented earlier this year at the European Society of Cardiology (ESC) meeting in Stockholm.² These initial data showed that AZD6140 was able to achieve greater and more consistent inhibition of platelet aggregation compared to clopidogrel 75 mg.

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Notes to Editors

AZD6140
AZD6140 is an investigational antiplatelet agent being studied for the prevention of thrombotic events in patient with ACS. AZD6140 is proposed to work by inhibiting the aggregation of platelets in the blood, which may reduce the risk of clot formation. AZD6140 is being studied as a reversible oral ADP receptor antagonist. It is proposed to selectively inhibit the P2Y₁₂ receptor, a key target receptor for ADP on platelets. AZD6140 is currently in phase II development.

The DISPERSE2 Study
The D ose confirmati on S tudy assessing anti-P latelet E ffects of AZD6140 vs. clopidogR el in patients with Non-S T Segment Elevation Acute Coronary Syndrome was a double-blind, double-dummy, parallel group, randomised, dose confirmation and feasibility study of AZD6140 plus ASA compared with clopidogrel plus ASA in 990 patients with non-ST elevation acute coronary syndromes. Subjects received aspirin up to 325 mg first dose, then 75 to 100 mg, and heparin/LMWH and/or GP IIb/IIIa inhibition per local physician. They were randomised to receive one of two doses of AZD6140 (90 mg or 180 mg twice daily) or clopidogrel 75 mg once daily for up to 12 weeks. Half of the AZD6140 patients were sub-randomised to receive a loading dose of 270 mg while the other half started therapy with the maintenance dose. Patients randomised to clopidogrel received a 300 mg loading dose unless they had been on previous clopidogrel therapy with the option to give an additional double blind clopidogrel 300 mg dose pre-PCI (total 600 mg dose).

Acute coronary syndrome (ACS)
ACS is an umbrella term for conditions that cause chest pain due to insufficient blood supply to the heart muscle (acute myocardial ischemia). ACS includes two conditions - unstable angina (chest pain with ECG changes compatible with ischaemia) and heart attack (non ST-elevation myocardial infarction). It is the most common reason for cardiac hospitalisation in the western world and is increasingly prevalent in many European countries.³ Patients with ACS are at increased risk from strokes and subsequent heart attacks.

AstraZeneca
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 world’s leading pharmaceutical companies with healthcare sales of over $21.4 billion and leading positions in sales of gastrointestinal, oncology, cardiovascular, neuroscience and respiratory products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. AstraZeneca has more than 40 years experience in cardiovascular medicine and aims to increase lifespan and improve quality of life by reducing the risk, prevalence and impact of cardiovascular disease. AstraZeneca has a comprehensive cardiovascular portfolio including CRESTOR™, EXANTA^TM , ATACAND^TM , ZESTRIL™, TENORMIN^TM , SELOKEN ZOK /TOPROL-XL^TM and PLENDIL^TM .

References:

References

1. Cannon CP, Husted S, Storey RF, Harrington RA, Watkins C, Hill S, Price D, Sanders N, Emanuelsson H, and Peters G. Safety, Tolerability and Preliminary Efficacy of AZD6140, the First Oral Reversible ADP Receptor Antagonist, Compared with Clopidogrel in Patients with Non-ST Segment Elevation Acute Coronary Syndrome (The DISPERSE2 Study). Presented at American Heart Association (AHA), Dallas, 15 November, 2005.

1. Husted S, Emanuelsson H, Heptinstall S, Clark S, and Peters G. Greater and Less Variable Inhibition of Platelet Aggregation (IPA) with AZD6140, the First Oral Reversible ADP Receptor Antagonist, Compared with Clopidogrel in Patients with Atherosclerosis (The DISPERSE Study). Presented at European Society of Cardiology (ESC), Stockholm, 7 September, 2005.
2. European Society of Cardiology. Acute Coronary Syndromes: www.escardio.org/knowledge/ehs/survey/ACS_II.htm