Spiriva® (tiotropium) improves quality of life in patients with COPD, TIPHON study

Ingelheim/Germany and San Diego, CA/USA, 24 May 2005 - Patients with Chronic Obstructive Pulmonary Disease (COPD)
experienced statistically and clinically significant improvements in health-related quality of life following nine months
treatment with first line maintenance therapy Spiriva® (tiotropium), according to the results of the TIPHON* study presented
today in San Diego, California at the International Conference of the American Thoracic Society.1


COPD is a progressive respiratory disease that causes significant deterioration of lung function and chronic breathlessness,
which is a major cause of disability associated with the disease.2 Chronic airflow limitation associated with COPD leads to
excess air being trapped in the lungs during exhalation. This process, known as "air trapping", is a primary cause of
breathlessness, which often restricts a patient's ability to perform daily activities, such as walking up stairs or taking a
shower.3,4 Currently, COPD is the fourth leading cause of death worldwide, claiming 2.75 million lives annually.5


"The TIPHON study results are encouraging because they show that treatment with Spiriva® can result in clinically significant
and sustained improvements in health-related quality of life for patients with COPD," said Andre-Bernard Tonnel, MD, Service
de Pneumologie et Immuno-Allergologie, Centre Hospitalier Regional et Universitaire de Lille and the study's lead
investigator. "Improved health status, or quality of life, is one of the main parameters for judging efficacy of prescribed
therapies in daily practice."


In this double-blind, placebo-controlled study, 554 patients with moderate COPD (mean FEV1>=1.36 L, 46.8% predicted) were
randomised to receive treatment with Spiriva® or placebo. Health-related quality of life was evaluated using the Saint
George's Respiratory Questionnaire (SGRQ), where a four-point decrease in SGRQ score is considered to be a clinically
meaningful improvement in a patient's health-related quality of life. The Visual Simplified Respiratory Questionnaire (VSRQ),
a new questionnaire awaiting validation that was developed specifically for this study using categorical rating scales, was
also used to evaluate health-related quality of life.


Results from TIPHON, the first study with tiotropium to assess change in health status as the primary endpoint, showed that1:



-- 23% more Spiriva® patients experienced a four-point improvement in SGRQ than those receiving placebo (59.1% vs. 48.2%;
p=0.029)


-- Spiriva® patients had a statistically significant improvement in their VSRQ score compared with those receiving placebo
(p=0.0004).


-- Spiriva®'s benefits were found to be independent of use of inhaled corticosteroids or reversibility status at entry into
the study















-- A significant improvement in the SGRQ total score with Spiriva® was seen throughout the course of the study, reaching a
pre-defined clinically meaningful improvement versus placebo at the end of the study.


The SGRQ questionnaire consists of three components: symptoms (measuring distress due to respiratory symptoms), activities
(effects of disturbance to mobility and physical activity caused by breathlessness) and impacts (assessing the psychosocial
impact of the disease on daily life and well being), which are weighted on a scale of 0 to 100 (100 representing the worst
possible state by the patient). A decrease in the SGRQ score indicates improvement. The VSRQ questionnaire contains eight
questions regarding health related quality of life topics. Categorical rating scales (from 0=extreme limitation to 10) are
used to collect the patient's answers. An increase in the VSRQ score indicates improvement.


In TIPHON, additional study findings in patients receiving treatment with Spiriva® included:


-- Significant and sustained improvements in lung function (at trough**) compared with the placebo group, including1:



FEV1 (forced expiratory volume in one second; +0.10L, p