June 3, 2005

Takeda Pharmaceutical Company Limited

Heart failure patients perceive improvement in symptoms on Candesartan treatment¹
Data showing Candesartan improves patients' perception of symptoms reinforces existing CHARM study data regarding physician-reported functional status improvements

OSAKA, JAPAN --- Takeda Pharmaceutical Company Limited ("Takeda") announced today that a new analysis of the CHARM (Candesartan in Heart Failure − Assessment of Reduction in Mortality and Morbidity) study data published in the European Journal of Heart Failure1 shows that patients treated with candesartan cilexetil ("candesartan"), a selective angiotensin receptor blocker (ARB), perceived greater improvement in their heart failure symptoms compared to those on placebo.

In this new analysis of 2,498 North American CHARM patients with symptomatic chronic heart failure (CHF), candesartan improved patient-reported well-being based on a self assessment questionnaire which evaluated the improvement in the level of daily activities carried out by patients and symptoms/feelings related to the patient's disease state. This follows previously published CHARM data demonstrating that candesartan was the first ARB to reduce both death and heart failure hospital admissions in heart failure patients with left ventricular systolic dysfunction.²The CHARM Programme also showed improvement in physician-reported New York Heart Association (NYHA) functional class in a broad spectrum of CHF patients.³

Commenting on this new analysis, Professor Karl Swedberg, Sahlgrenska University Hospital/östra, Göteborg, Sweden, Co Chairman of the CHARM Programme said, "The patient's perception of treatment effect is of additional value and complementing the physician's assessment of functional status in chronic heart failure. This new analysis from CHARM provides further evidence regarding the benefit of candesartan therapy in these patients by demonstrating that they feel better as well as being able to undertake daily tasks more easily. This is a very important factor in clinical practice, often leading to better adherence to treatment and greater satisfaction with care."

The McMaster Overall Treatment Evaluation (OTE) scoring system was used in this study, at intervals of 6, 14 and 26 months following randomization and at the final visit to assess improvement. Results show that 37.7% of candesartan patients perceived an overall improvement in symptoms compared to 33.5% for placebo and the improvement was ranked as moderate or better (moderately, a good deal, a great deal or a very great deal) by 27.6% in the candesartan group compared to 23.9% for placebo.¹
Of patients reporting an improvement in their condition, 51.3% in the candesartan group considered this improvement to be very or extremely important, compared to 46.4 for  placebo.¹ Fewer candesartan patients reported a deterioration in OTE score compared to placebo (10.8% vs. 12.0%).

In November 2004, candesartan, already a well-established antihypertensive therapy, was granted EU* Marketing Authorization 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.

These approvals of a CHF indication for candesartan are based on the positive results of the CHARM clinical trial Programme, first presented at the European Society of Cardiology (ESC) Congress in August 2003. 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.²

CHARM study was sponsored and conducted by AstraZeneca.

*The MRP on this occasion covers all EU countries apart from France. The reference member state during this procedure has been 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).

Candesartan cilexetil was discovered and originally synthesized by Takeda Pharmaceutical Company Ltd. 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 Ltd.

References

• *1.O'Meara E, Eldrin L, Granger C, et al. Patient perception of the effect of treatment with candesartan in heart failure. Results of the candesartan in heart failure:Assessment of reduction in mortality and morbidity (CHARM) programme. The European Journal of Heart Failure, June 3 2005.
• *2.Young JB, Dunlap ME, Pfeffer MA, et al. Mortlaity and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic function. Results from the CHARM low-left ventricular ejection fraction trials. Circulation 2004;110:2618-26.
• *3.O'Meara E, Solomon SD, McMurray JJV, et al. Effect of candesartan on New York heart association functional class. Results of the candesartan in heart failure: Assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J in press.

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