Boehringer Ingelheim Corporation Release: Data for Investigational Tiotropium Show Improved Lung Function and Sustained Bronchodilation in Patients With Moderate Asthma Severity

RIDGEFIELD, Conn., Sept. 10, 2013 /PRNewswire/ -- Boehringer Ingelheim will present a pooled analysis of new data from the Phase 3 UniTinA-asthma^® program at the European Respiratory Society (ERS) Annual Congress 2013 in Barcelona. The data from the individual MezzoTinA-asthma^® Phase 3 studies (NCT01340209 and NCT00565266), from which the pooled data are derived, show the addition of tiotropium delivered via the Respimat^® inhaler to medium-dose maintenance inhaled corticosteroid (ICS) therapy (defined as 400-800 mcg budesonide/day or equivalent) improved lung function and provided sustained bronchodilation over 24 hours in patients with moderate asthma and airflow limitation.Tiotropium is being investigated to determine the medicine's efficacy in treating asthma patients and is not currently approved for this indication.

These new data from the MezzoTinA-asthma^® Phase 3 studies also showed the addition of once-daily tiotropium delivered via the Respimat^® inhaler provided a statistically significant improvement in asthma control responder rate, as measured by the Asthma Control Questionnaire (ACQ).

"These results give us insight into the potential efficacy of tiotropium in the subset of asthma patients who remain symptomatic despite using medium-dose ICS and show that the addition of tiotropium may provide improvements in asthma control and lung function that could be clinically meaningful," said lead study author Professor Huib A.M. Kerstjens of the University Medical Centre, Groningen, The Netherlands. "A significant proportion of asthma patients treated with ICS, as recommended in the guidelines, continue to experience symptoms that can impact their ability to lead a full life."

Despite current treatment options, at least 40 percent of patients with asthma remain symptomatic and may experience potentially life-threatening asthma exacerbations (attacks).

"We are committed to studying tiotropium across a wide range of asthma patients from mild to severe across all age groups, and we are encouraged by the results we have seen with tiotropium in asthma to date," said Tunde Otulana, MD, senior vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Results from the MezzoTinA-asthma^® studies presented at ERS build on previous positive study results for tiotropium from the PrimoTinA-asthma^® studies in patients with severe asthma. Collectively, these results show tiotropium, when approved, could become an important new option for asthma patients across a range of severities who remain symptomatic despite current standard treatments."

Key Results from the MezzoTinA-Asthma^® Phase 3 Studies
The data are from a set of replicate Phase 3 studies; MezzoTinA-asthma^® 1 and MezzoTinA-asthma^® 2 are two paired international, double-blind, randomized, placebo- and active-controlled, parallel-group trials that involved asthma patients ages 18-75 years who remained symptomatic while on medium-dose ICS. A total of 2,103 patients were randomized to receive tiotropium 2.5 mcg or 5 mcg once daily delivered via the Respimat^® inhaler, salmeterol 50 mcg twice daily (as the active comparator), or placebo, for 24 weeks. Pre-specified co-primary endpoints were peak forced expiratory volume (FEV₁)_(0-3h) response and trough FEV₁ response after 24 weeks. ACQ responder rate was the third co-primary endpoint, performed on the pooled MezzoTinA-asthma^® results.

In the individual trials and the pooled analysis being presented at ERS, the mean change in peak FEV₁ at 24 weeks from baseline versus placebo was significantly improved for all three active treatments:

Additionally, the mean change in trough FEV₁ at 24 weeks from baseline versus placebo in the individual trials, as well as in the pooled data being presented at ERS, was significantly improved for all three active treatments:

To characterize the treatment response as greater than or equal to 0.5, measured by the ACQ, treatment with tiotropium (either 2.5 mcg or 5 mcg) resulted in a statistically significant improvement in the ACQ responder rate at 24 weeks compared with placebo and comparable to that of salmeterol. ACQ responder rates, performed on the pooled MezzoTinA-asthma results, were as follows:

• Placebo: 57.7 percent (n=299/518)
• Tiotropium 2.5 mcg once daily: 64.5 percent (n=332/515; P = 0.03)
• Tiotropium 5 mcg once daily: 64.3 percent (n=330/513; P = 0.03)
• Salmeterol 50 mcg twice daily: 66.5 percent (n=356/535; P = 0.004)

Patients in the MezzoTinA-asthma^® studies were permitted to receive additional background therapy, including antihistamines, nasal steroids and leukotriene modifiers. Long-acting beta agonists (LABAs) were not permitted during the study (salmeterol was included as an active comparator for the trial).

Adverse events were balanced across the four treatment groups groups in the pooled analysis with 58.2 percent of patients receiving tiotropium 2.5 mcg once daily reporting an adverse event compared to 57.3 percent of patients in the tiotropium 5 mcg once daily group, 54.3 percent of patients who received salmeterol 50 mcg twice daily and 59.1 percent of patients receiving placebo. The most commonly reported adverse events* were asthma, peak expiratory flow (PEF) rate decreased, nasopharyngitis and upper respiratory tract infection.

About the UniTinA-Asthma^® Clinical Trial Program
The MezzoTinA-asthma^® studies are a part of the comprehensive Phase 3 trial program, UniTinA-asthma^®, which includes a number of clinical trials in adults, adolescents and pediatric patients across different asthma severities who remain symptomatic on current treatment with ICS. The program includes over 4,000 patients in more than 150 sites globally. Results from the PrimoTinA-asthma^® studies in severe asthma patients, part of the UniTinA-asthma^® program, were presented at the 2012 ERS Congress in Vienna, Austria, with additional sub-analyses presented at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting and the American Thoracic Society (ATS) International Conference.

About Asthma
Asthma is a chronic disease characterized by airway inflammation and bronchoconstriction. When a person with asthma comes into contact with an asthma trigger (e.g. infections, pollen, smoke), their airways can become inflamed, swollen and constricted and excess mucus is produced. These reactions can cause the airways to become narrower and irritated, making it difficult to breathe. People suffering from asthma experience recurrent episodes of wheezing, breathlessness, chest tightness and coughing. Asthma attacks occur when symptoms become more intense or frequent.

As of December 2012, an estimated 300 million people worldwide suffer from asthma. Estimates have shown that the number of people with asthma could grow by an additional 100 million people worldwide by 2025.

By avoiding asthma triggers, one can help to reduce the severity of asthma. Although asthma cannot be cured, appropriate management can control the disease in many patients. However, at least 40 percent of patients still suffer from uncontrolled asthma and may experience life-threatening asthma exacerbations despite the available treatment options. They can continue to have symptoms and lifestyle restrictions and might even require emergency care.

Leading Respiratory Forward
Through research, treatments and patient-centric support services, the Boehringer Ingelheim lung health portfolio is designed to help address the challenges people living with a lung disease face every day. Leveraging the company's cutting edge science and leadership in chronic obstructive pulmonary disease (COPD), Boehringer Ingelheim is researching new treatment approaches where needs persist. It is the company's goal to make a difference in the lives of patients with COPD, asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory diseases.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim has a demonstrated commitment to corporate social responsibility. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

For more information please visit www.us.boehringer-ingelheim.com

* Adverse events reported by Preferred Term; MedDRA v 15.1 was used

SOURCE Boehringer Ingelheim