New analysis supports tiotropium as initial maintenance therapy for COPD

Vienna/Austria, 15 September 2009 – A new post-hoc analysis of data from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT^®) trial presented today at the European Respiratory Society (ERS) Annual Congress demonstrated that tiotropium (Spiriva^®) administered to younger patients (≤50 years old) with Chronic Obstructive Pulmonary Disease (COPD) results in statistically significant reductions in the rate of lung function decline [as measured by forced expiratory volume in one second (FEV₁)] and improvements in health-related quality of life [as measured by St George’s Respiratory Questionnaire (SGRQ)]. This younger patient population showed a 34% reduction in the rate of lung function decline over 4 years when treated with tiotropium compared to age-matched controls (post-bronchodilator FEV₁, 38 mL/year vs. 58 mL/year; p=0.01). ^*1

The data, based on 356 patients ≤50 years old enrolled in the landmark UPLIFT^® trial, also demonstrated that younger patients treated with tiotropium experienced a 27% decreased risk of exacerbations compared with patients in the control group [HR (95%CI) = 0.73 (0.56, 0.95); p=0.02]. Exacerbations can worsen the clinical course of the disease, therefore a treatment such as tiotropium that significantly reduces the number of COPD exacerbations may provide patients with an improved disease prognosis and impact the clinical course of COPD.²

“These new data in younger patients reinforce the imperative to diagnose and treat COPD patients earlier, which is meaningful to both physicians and patients. Doctors can prescribe tiotropium with confidence in patients younger than 50, to help them experience improved quality of life and long-term improvement. These data illustrate tiotropium’s efficacy in potentially preserving lung function and impacting the course of the disease in younger patients.” said Professor Roland Buhl, Head of the Pulmonary Department at the University of Mainz, Germany.

Further evidence from UPLIFT^® highlights benefit of early treatment
Further evidence supporting tiotropium as initial maintenance therapy,consistent with Global Initiative for Chronic Obstructive Lung Disease(GOLD) guidelines³, came from a post-hoc analysis of maintenance-naïve patients in UPLIFT^® which was presented at the American Thoracic Society (ATS) Annual Congress in 2009. This analysis evaluated the effectiveness of tiotropium in COPD patients who had not received previous maintenance therapy with inhaled long-acting β-2 agonists, inhaled corticosteroids, the ophyllines or anticholinergics.⁴ The results in 403 patients receiving tiotropium and 407 control patients^* showed that tiotropium significantly reduced the rate of lung function decline (as measured by FEV₁) and produced a statistically significant improvement in health-related quality of life (as measured by SGRQ). In addition, the risk of hospitalisations due to COPD exacerbations was also significantly reduced in patients receiving tiotropium compared with patients in the control group [HR (95% CI) = 0.77 (0.62, 0.94); p=0.012].

Tiotropium may slow the progression of COPD in patients with early stage disease (GOLD Stage II), as measured by the rate of decline in lung function. A pre specified subgroup analysis of UPLIFT^® recently published in the Lancet showed that tiotropium reduced the rate of decline in postbronchodilator FEV₁ over 4 years compared with control (43 mL per year vs. 49 mL per year; p=0.024). The rate of decline in prebronchodilator FEV₁ was similar between the groups.⁵ Tiotropium also resulted in an 18% lower risk for exacerbations and 20% fewer exacerbations (p<0.0001) compared with control. GOLD Stage IIis typically when patients start to realise their lung function is abnormal and experience breathlessness on exertion. Patients generally first seek treatment from their primary care physician for COPD symptoms at this stage.³

“Overall, the growing body of evidence around tiotropium highlights its efficacy as a first line maintenance therapy in the treatment of younger patients and in those in the earlier stages of COPD. Through earlier diagnosis and treatment with tiotropium, we can have a positive impact on patient outcomes,’ said Professor Buhl.

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.³ 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 2005⁶ - more than breast cancer and diabetes combined.⁷ Dyspnoea (breathlessness), the main symptom of COPD, is characteristically persistent and progressive and has a serious impact on patients’ quality of life.³ At its most severe, it even limits a patient from performing simple tasks such as washing and dressing.

About UPLIFT^®
The four-year study was a multicentre (470 sites), multinational (37 countries), randomised, double-blind, placebo-controlled,parallel-group trial which commenced in December 2002. The study included 5,993 male and female COPD patients. Patients were randomised 1:1 to receive either 18 μg 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.⁸ 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 alterthe rate of decline in lung function in the overall clinical trial population.⁸

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.^9,10 It is the most prescribed medication for the treatment of COPD in the world.

Tiotropium works through targeting of 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.

Tiotropium has demonstrated significant and sustained bronchodilation (opening of the airways)¹¹ and reduction in hyperinflation (air trapping).^12,13 In placebo-controlled studies, patients treated with tiotropium had less activity-induced breathlessness and improved exercise endurance.⁹ They required fewer doses of rescue medications, had fewer exacerbations and COPD-related hospitalizations.¹¹ In clinical trials, the most common adverse reaction reported with tiotropium was dry mouth, which was usually mild and often resolved spontaneously during treatment.¹¹ 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.³

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.

^* All patients were allowed to continue with their normally prescribed respiratory medication, including dose adjustment throughout the trial, except inhaled anticholinergics.