May 20, 2005

Takeda Pharmaceutical Company Limited

FDA Approves Candesartan Cilexetil for Use with an ACE Inhibitor in the Treatment of Heart Failure
Candesartan is the only ARB proven to provide benefits when added to conventional heart failure therapy, including ACE inhibitors plus beta blockers

OSAKA, JAPAN --- Takeda Pharmaceutical Company Limited ("Takeda") announced today that the US Food and Drug Administration (FDA) has approved a new use for its angiotensin receptor blocker (ARB) candesartan cilexetil, which is sold as ATACAND by AstraZeneca in the US, for the treatment of heart failure (NYHA class II-IV) in patients with left ventricular systolic dysfunction (ejection fraction ≦ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations.
Candesartan also has an added effect on these outcomes when used with an ACE inhibitor.

Candesartan is now the first ARB proven to provide these benefits with or without an ACE inhibitor and is the only ARB with proven benefit when used with conventional therapy that includes both an ACE inhibitor plus a beta-blocker.

The current label change follows the unanimous recommendation for approval by the Cardio-Renal Advisory Committee to the FDA on February 24, 2005. This approval was based primarily on results from the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity-Added Trial (CHARM-Added), which examined the effect of Candesartan (n=1276) compared to placebo (n=1272) in 2,548 heart failure (HF) patients who were already receiving conventional therapy including an ACE inhibitor. The study demonstrated that the addition of Candesartan resulted in a 15% relative-risk reduction in cardiovascular death or heart failure hospitalization (538 events in the placebo arm compared to 483 events in the patients receiving Candesartan, [p=0.011]), with both components contributing to this effect.

The recommended initial dose of Candesartan for the treatment of heart failure is 4 mg once daily. The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2 week intervals, as tolerated by the patient.

CHARM study was sponsored and conducted by AstraZeneca. Candesartan was discovered and originally synthesized by Takeda, and it was jointly developed with AstraZeneca. Candesartan is marketed worldwide under the brand name of Blopress® by Takeda and Atacand® by AstraZeneca in more than 70 countries.

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 is a global research-based pharmaceutical company, largest in Japan and one of the leaders in the world. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products.

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