28 August 2009 – A new analysis of the landmark UPLIFT ^® trial, published today in the Lancet, shows that tiotropium (Spiriva ^® Handihaler ^® 18 µg) administered to Chronic Obstructive Pulmonary Disease (COPD) patients with moderate disease severity (GOLD – Global Initiative for Chronic Obstructive Lung Disease – Stage II) produced significant and sustained improvements in lung function for up to 4 years. ¹ This pre-specified subgroup analysis involved 2,739 patients - the largest group of early stage COPD patients treated with a long-acting anticholinergic in a randomised, placebo-controlled study.

The new UPLIFT ^® analysis shows that in patients with GOLD Stage II COPD, tiotropium may slow the progression of COPD as measured by the rate of decline in lung function. Tiotropium reduced the rate of decline in postbronchodilator FEV ₁^* over 4 years compared with control _** (43 mL per year vs. 49 mL per year; p=0.024). The rate of decline in prebronchodilator FEV ₁^* was similar between the groups.

Improvements in pre- and postbronchodilator FEV ₁ were maintained vs. control throughout the trial (101-119 mL and 52-82mL respectively; p<0.0001). GOLD Stage II patients taking tiotropium had an 18% lower risk for exacerbations and 20% fewer exacerbations (p<0.0001) compared with control. Health-related quality of life, as measured by the St. George’s Respiratory Questionnaire (SGRQ), was better in patients treated with tiotropium than in control patients throughout the study (p≤0.006). There was also a trend for reduced mortality with tiotropium compared with control. ¹

“These results are very important for clinical practice because this is the first large, long-term study to show that treatment with along-acting anticholinergic has substantial benefits in patient in the early stages of COPD. UPLIFT has shown that a significant decline in lung function occurs early in the disease, and it is known that exacerbations accelerate disease progression. Therefore this new analysis confirms that we should treat COPD in the early stages with a medication such as tiotropium that can improve lung function and quality of life, and reduce exacerbations,” said Professor MarcDecramer, UPLIFT lead investigator, Professor of Medicine and Chief of the Respiratory Division at the Katholieke Universiteit Leuven, Belgium.

The social and economic burden of COPD increases steadily, with patients becoming less independent as the disease gets worse. ² GOLD Stage II is typically when patients may start to realise their lung function is abnormal and experience breathlessness on exertion. As COPD progresses, lung function continues to decline and physical activity becomes severely limited, disrupting the patients’ and their caregivers’ ability to lead a full life, interfering with every daytasks and participation in family routines. ² This can lead to people feeling afraid, anxious, frustrated, isolated and depressed. ^2,3 It is therefore important to ensure that patients are diagnosed and treated as early as possible, including smoking cessation.

“The results from the UPLIFT analysis in GOLD Stage II patients are extremely heartening. They clearly demonstrate that if patients seek treatment from their primary care physicians earlier they may be able to impact the clinical course of their disease and improve their quality of life,” said Dr. Anders Østrem, Specialist in Family Medicine, Norway and Director, International Primary Care RespiratoryGroup.

Notes to Editors
About COPD
COPD is a progressive yet treatable disease that restricts patients’ lives over time and is a major cause of death and disability throughout the world. Symptoms include cough, sputum (mucus or phlegm) production, and breathlessness on exertion. Worsening of these symptoms often occurs and can restrict a patient’ s ability to perform normal daily activities. ² The latest World Health Organization (WHO) figures estimate that 210 million people are currently living with COPD and more than 3 million people died from the disease in 2005 ⁴ - more than breast cancer and diabetes combined. ⁵ Dyspnoea (breathlessness), the main symptom of COPD, is characteristically persistent and progressive and has a serious impact on patients’ quality of life. ² At its most severe, it even limits a patient from performing simple tasks such as washing and dressing.

About UPLIFT ^®
UPLIFT ^® ( Understanding Potential Long-term Impacts on Function with Tiotropium) was a four-year, multicentre (470 sites), multinational (37 countries), randomised, double-blind, placebo-controlled, parallel-group trial which commenced in December 2002. The study included 5993 male and female COPD patients. Patients were randomised 1:1 to receive either 18μg tiotropium or placebo once daily. In both arms, patients were allowed to take all other respiratory medications usually prescribed for the treatment of COPD, except for inhaled anticholinergics. Results of the UPLIFT ^® trial demonstrated that tiotropium produced sustained improvements in lung function for up to 4 years (p<0.001),although it did not alter the rate of decline in lung function. ⁶

About tiotropium (Spiriva ^®)
Tiotropium, a long-acting inhaled anticholinergic medication, is the first inhaled treatment to provide significant and sustained improvements in lung function with once-daily dosing. Tiotropium positively impacts the clinical course of COPD, helping to change the way patients live with their disease. ^7,8 It is the most prescribed medication for the treatment of COPD in the world.

Tiotropium works through targeting a dominant reversible mechanism of COPD – cholinergic bronchoconstriction. Tiotropium helps COPD patients breathe easier by opening narrowed airways and helping to keep them open for 24 hours. ⁹

Tiotropium has demonstrated significant and sustained bronchodilation(opening of the airways) and reduction in hyperinflation (air trapping). ^10,11 In placebo-controlled studies, patients treated with tiotropium had less activity-induced breathlessness and improved exercise endurance. ⁷ They required fewer doses of rescue medications, had fewer exacerbations and COPD-related hospitalizations. ⁹ In clinical trials, the most common adverse reaction reported with tiotropium was dry mouth, which was usually mild and often resolved spontaneously during treatment. ⁹ Long-acting bronchodilators, including tiotropium, are a preferred maintenance therapy for COPD from stage II onwards according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines. ²

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.

Pfizer Inc: Working together for a healthier world™
Founded in 1849, Pfizer is the world`s premier biopharmaceutical company taking new approaches to better health. We discover, develop,manufacture and deliver quality, safe and effective prescription medicines to treat and help prevent disease for both people and animals. We also partner with healthcare providers, governments and local communities around the world to expand access to our medicines and to provide better quality health care and health system support. At Pfizer, colleagues in more than 90 countries work every day to help people stay happier and healthier longer and to reduce the human and economic burden of disease worldwide.

* FEV1 = Forced expiratory volume in one second. Postbronchodilator FEV1 was measured after giving the study drugs - tiotropium or placebo- and additional administration of short acting bronchodilators. Prebronchodilator FEV1 was measured before administration of study drugs.
** All patients from both the tiotropium group and the control group were allowed to continue with their normally prescribed respiratory medication, including dose adjustment throughout the trial, except inhaled anticholinergics.