October 12, 2005

Takeda Pharmaceutical Company Limited

Risk of heart attack and cardiovascular death significantly reduced by Candesartan therapy in patients with heart failure

October 12, 2005, Osaka, Japan: Data published in the Journal of the American Medical Association, JAMA today show that candesartan cilexetil ("candesartan") is the first angiotensin receptor blocker (ARB) to significantly reduce cardio-vascular death and nonfatal myocardial infarction (MI) in heart failure patients compared to placebo.

A new analysis of the CHARM (Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity) study programme at a median follow up time of 37.7 months shows the composite endpoint of cardiovascular death or nonfatal MI was significantly reduced in patients receiving candesartan compared to the placebo group, 20.4% vs. 22.9% respectively (Hazard ratio [HR] 0.87, 95 % confidence interval [CI], 0.79-0.96; p=0.004). Nonfatal MI alone was also significantly reduced in the candesartan group, 3.1% vs. 3.9% in the placebo group (HR 0.77, 95% CI, 0.60-0.98;p=0.03).

Lead author Dr Catherine Demers of McMaster University, Ontario, Canada commented on these new data: "Translated into patient benefit, these findings mean that one cardiovascular death or heart attack is prevented for every forty patients treated with candesartan for just over three years. The results support the use of cande-sartan in a broad spectrum of heart failure patients including those receiving standard optimal therapy.

The reduction of cardiovascular death or nonfatal MI in the actively treated group was consistent across relevant subgroups and the component trials in the CHARM study programme including patients treated with other therapies proven to be effective in reducing the risk of MI or reinfarction.

In November 2004, Candesartan, already a well-established antihypertensive therapy, was granted EU* Marketing Authorisation for the treatment of patients with heart failure and left ventricular systolic dysfunction.In February 2005 the US Food and Drug Administration (FDA) approved candesartan for the treatment of heart failure (New York Heart Association Class II-IV and ejection fraction less than or equal to 40 percent). On 19 May 2005 the FDA also approved candesartan for use on top of ACE-inhibitors in the treatment of heart failure. Candesartan is now approved for the treatment of heart failure in 49 countries.

These approvals of a CHF indication for candesartan are based on the positive results of the CHARM study programme. The results from CHARM identified candesartan as the first ARB to reduce both death and heart failure hospital admissions in chronic heart failure patients with left ventricular systolic dysfunction, irrespective of background therapy.

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Notes to editors

• • Candesartan cilexetil was discovered and originally synthesized by Takeda Pharmaceutical Company Limited and it was jointly developed with AstraZeneca.
• • Candesartan cilexetil is marketed by Takeda as Blopress®, Amias® and Kenzen®, and by AstraZeneca as Atacand® under the license from Takeda Pharmaceutical Company Limited.
• • CHARM study was sponsored and conducted by AstraZeneca.
• • *The MRP on this occasion covered all EU countries apart from France. The reference member state during this procedure was the UK. (* EU countries excluding France and prior to 2004 expansion. Belgium, Denmark, Germany, Greece, Spain, Ireland, Italy, Luxembourg, Netherlands, Austria, Portugal, Finland, Sweden, United Kingdom).

About CHARM

The CHARM Programme, which recruited 7,601 patients, was conducted in heart failure with an AT1-receptor blocker. Patients with classic symptomatic chronic heart failure − depressed left ventricular (LV) systolic function (Left Ventricular Ejection Fraction (LVEF) < 40%), were randomized into one of two studies − either an ACE-inhibitor intolerant population (CHARM-Alternative), or the population treated with ACE-inhibitors (CHARM-Added). In addition, patients with preserved LV systolic function (LVEF> 40%) were also randomized into a third study (CHARM-Preserved). All patients received either candesartan cilexetil or placebo.

About Takeda

Takeda, located in Osaka, Japan, is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products.

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