AstraZeneca submits regulatory application in Europe for use of Atacand(R) in heart failure

Mölndal, Sweden, 7 April – AstraZeneca today announced the submission of a regulatory application in the European Union (EU), as part of the Mutual Recognition Variation Procedure to obtain a new indication for Atacand (candesartan cilexetil), its angiotensin II type 1 (AT1) receptor blocker, for use in the treatment of heart failure. The UK acts as the RMS (Reference Member State). Further filings in the US and other markets are expected in the near future.

This submission follows the positive results of the CHARM (Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity) Programme, first presented at the European Society of Cardiology (ESC) in August 2003. CHARM proved Atacand, as the first AT1-receptor blocker, to reduce both cardiovascular deaths as well as hospital admissions, across a broad spectrum of patients with chronic heart failure1.

Additional analyses of the CHARM data, presented at the ACC (American College of Cardiology Meeting, New Orleans, 7-10 March), added further evidence for the benefits of Atacand in CHF. One analysis2 found that New York Heart Association (NYHA) functional class improved in a broad spectrum of CHF patients treated with Atacand.

Commenting on the heart failure submission for Atacand, Gunnar Olsson, VP and Head of the Cardiovascular Therapy Area said: "Heart failure remains a very serious, costly condition and there is still a real need for additional, effective therapies. It is a major cause of death, hospital admissions and self-reported quality of life is impaired more by CHF than by any other common chronic medical disorder3,4." He continued: "AstraZeneca is delighted that CHARM has shown that Atacand can benefit a broad range of heart failure patients. This file submission is a step further towards Atacand becoming available to doctors as a new and effective treatment option, offering more benefits to patients both in terms of better outcomes, including improved symptom control, reduced mortality, better quality of life, and better tolerability."

Atacand is an angiotensin II type 1 (AT1) receptor blocker indicated for the treatment of high blood pressure. As proven and leading antihypertension therapy, Atacand was first licensed in 1997 and has been shown to lower blood pressure more effectively than losartan, the initially introduced AT1-receptor blocker 5,6,7,8. Recent clinical outcome studies with Atacand, SCOPE and CHARM, have demonstrated the clinical value of the medicine in hypertension and heart failure, strengthening the position of Atacand as the premier AT1-receptor blocker in its class.

For more information, please visit www.astrazenecapressoffice.com or contact:

Elizabeth Rickard - Ketchum
Mobile: 44-778-624-6618
Office: 44-207-611-3633
Email: elizabeth.rickard@ketchum.com

Anette Orheim - AstraZeneca
Mobile: 46-709-13-1952
Office: 46-46-33-8087
Email:anette.orheim@astrazeneca.com

References:

1.Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJV, Michelson EL et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362:759-66

2. McMurray JJ, Östergren J, Olofsson B, Granger CB, Michelson E, Young JB et al. Candesartan improves functional class across a broad spectrum of patients with chronic heart failure: Results of the Candesartan in Heart Failure- Assessment of Reduction in Mortality and Morbidity Programme (CHARM). J Am Coll Cardiol 2004;43 (suppl 5):206A

3. Stewart AL, Greenfield S, Hays RD, Wells K, Rogers WH, Berry SD et al. Functional status and well-being of patients with chronic conditions – results from the medical outcomes study. JAMA 1989;262:907-43

4. Fryback DG, Dasbach EJ, Klein R, Klein BE, Dorn N, Peterson K et al. The Beaver Dam Health Outcomes Study – initial catalog of health-state quality factors. Med Des Making 1993;13:89-102

5. Andersson OK, Neldam S. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Blood Press 1998; 7:53-9

6. Lacourciere Y, Asmar R. A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Candesartan/Losartan study investigators. Am J Hypertens 1999; 12:1181-7.

7. Bakris G, Gradman A, Reif M, Wofford M, Munger M, Harris S, et al. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. J Clin Hypertens 2001;3:16–21

8. Vidt DG, White WB, Ridley E, Rahman M, Harris S, Vendetti J, et al. CLAIM Study Investigators. A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II. J Hum Hypertens 2001;15:475–80

Notes to editors:

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 $18.8 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. 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™, Atacand ™, ZESTRIL™, TENORMIN™, SELOKEN® ZOK /TOPROL-XL™ and Plendil ™ This heritage is complemented by an innovative pipeline including the first oral direct thrombin inhibitor, Exanta ™, and a novel treatment for type 2 diabetes / metabolic syndrome, GALIDA ™.

Candesartan Cilexetil is marketed by AstraZeneca under trademark Atacand®. Atacand® is manufactured under agreement from Takeda Chemical Industries Ltd.

AstraZeneca is the developer and sole sponsor of the CHARM programme. The CHARM Programme, which recruited 7,601 patients, is the largest ever trial programme conducted in heart failure with an AT1-receptor blocker. Patients were randomised to either Atacand® or placebo in a 1:1 ratio in each of the three component studies. The CHARM results showed that Atacand is the first Angiotensin Receptor Blocker (ARB) to increase survival in chronic heart failure patients with left ventricular dysfunction, whether or not they are taking an ACE-inhibitor. In patients who were not taking ACE-inhibitors due to previous intolerance, Atacand significantly reduced the risk of cardiovascular death or hospitalisation for chronic heart failure, the relative risk reduction being 23% (p<0.0004). Also in patients who were prescribed conventional therapy for chronic heart failure including an ACE inhibitor, Atacand demonstrated mortality and morbidity benefits. Atacand produced a relative risk reduction of cardiovascular death or hospitalisation for chronic heart failure of 15% (p=0.011) when compared to conventional treatment alone. The CHARM Programme also included the largest completed trial in chronic heart failure patients with preserved LV function, patients for whom little evidence based treatment guidance presently exist. In CHARM-Preserved the primary endpoint of cardiovascular death or hospitalisations for chronic heart failure showed a trend, 11% relative risk reduction in favour of Atacand (p=0.118), consistent with the significant findings seen in the other two studies. Pooled analysis of the three studies showed that Atacand provided a significant reduction in cardiovascular death and also demonstrated a positive trend in the overall reduction in all cause mortality approaching statistical significance (p=0.055).

New York Heart Association (NYHA) Classification is a widely used and validated measure of symptomatic limitation in CHF and improving well-being is a key objective of heart failure treatment.
Class I: No limitation. Ordinary physical exercise does not cause fatigue, dyspnoea (breathlessness) or palpitations
Class II: Slight limitation of physical activity. Comfortable at rest but ordinary physical activity results in symptoms
Class III: Marked limitation of physical activity. Comfortable at rest but less than ordinary activity results in symptoms
Class IV: Unable to carry out any physical activity without discomfort. Symptoms present even at rest with increased discomfort with any physical activity

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