Boehringer Ingelheim Pharmaceuticals, Inc.'s Landmark Tiospir ™ Trial Demonstrates Comparable Long-Term Safety of Tiotropium Delivered Via Respimat ® and Handihaler ® in COPD Patients

Landmark TIOSPIR™ trial demonstrates comparable long-term safety of tiotropium delivered via Respimat® and HandiHaler® in COPD patients

RIDGEFIELD, Conn., Sept. 8, 2013 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced the results of TIOSPIR (Tiotropium Safety and Performance in Respimat) (NCT01126437), one of the largest international chronic obstructive pulmonary disease (COPD) trials conducted to date, at the European Respiratory Society (ERS) Annual Congress 2013 in Barcelona, Spain. The results, based on data from a patient database of more than 17,000 COPD patients from 50 countries, demonstrated the non-inferiority of tiotropium Respimat^® 5 µg and 2.5 µg once-daily compared to Spiriva^®HandiHaler^® (tiotropium bromide inhalation powder) 18 µg once-daily on all-cause mortality outcomes in COPD patients.SPIRIVA HandiHaler is currently the most prescribed COPD maintenance therapy in the United States and worldwide.

The Respimat^® Inhaler is a propellant-free inhaler that uses mechanical energy to generate a soft, slow-moving mist to deliver the same active ingredients in SPIRIVA HandiHaler. Tiotropium Respimat^®is under clinical development and is not yet approved in the United States. Boehringer Ingelheim is pursuing U.S. Food and Drug Administration (FDA) approval of tiotropium Respimat^®in order to expand its respiratory portfolio to provide COPD patients with innovative technology to meet some of the growing needs in respiratory care.

"TIOSPIR provides a robust data set that adds to the long term safety and efficacy profile of tiotropium delivered by either HandiHaler^® or Respimat^®," said Antonio Anzueto, MD, trial investigator and Professor of Medicine Pulmonary/Critical Care Medicine, University of Texas Health Science Center at San Antonio, Texas. "Importantly, this large trial studied a representative population of real-world COPD patients, including those with a history of cardiac disease who are often left out of studies, and now provides strong evidence to support the safety profile of tiotropium among these patients."

The highly anticipated results from the three-year trial were also published in the New England Journal of Medicine on September 8, 2013.

"These are very exciting data as they provide extensive information on the safety of tiotropium delivered via the Respimat^® Inhaler," said Tunde Otulana, MD, senior vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "The findings of the TIOSPIR study strongly support our pursuit of approval for tiotropium Respimat^® in the United States, and provide Boehringer Ingelheim with the confidence to continue studying this innovative delivery system with other investigational respiratory therapies in our portfolio."

The Respimat^® device is currently approved for use in the United States with another Boehringer Ingelheim respiratory therapy, Combivent^® Respimat^® (ipratropium bromide and albuterol). The company is also continuing ongoing clinical trials to develop Respimat^® with other investigational respiratory agents in COPD and asthma.

DETAILED TIOSPIR FINDINGS

Safety as measured by survival rates
The three-year TIOSPIR trial showed both tiotropium Respimat^®doses to be non-inferior to Spiriva^®HandiHaler^® (tiotropium bromide inhalation powder) with comparable impact on all-cause mortality for all tiotropium formulations/doses tested in the study (tiotropium 5 µg, tiotropium 2.5 µg, HandiHaler^® 18 µg).

Importantly TIOSPIR also demonstrated that:

• The incidence of adverse events and major adverse cardiovascular events was similar between the treatment groups
• In patients with a history of cardiac arrhythmia, tiotropium Respimat^® 5 g and Spiriva^®HandiHaler^® (tiotropium bromide inhalation powder) 18 µg showed similar impact on survival as measured by all-cause mortality

Efficacy as measured by time to first COPD exacerbation
COPD exacerbations have a significant impact on patients' lives and reducing their frequency and severity are principal goals of COPD treatment. Tiotropium Respimat^® 5 g was also shown to not be superior to SPIRIVA HandiHaler for prevention of COPD exacerbation in the TIOSPIR trial, with both treatment groups having comparable results for time to first COPD exacerbation. In particular, the median time to COPD exacerbation for tiotropium Respimat^® 5 µg (once-daily, two inhalations of 2.5 µg) was 756 days compared to 719 days for SPIRIVA HandiHaler 18 µg.

The TIOSPIR results also demonstrate that Respimat^® and HandiHaler^®have comparable results for exacerbation frequency, as well as rate of COPD exacerbations associated with hospitalization.

About TIOSPIR
TIOSPIR was designed to directly compare the safety of tiotropium Respimat^® to SPIRIVA HandiHaler. It was determined that a long-term head-to-head study was the most appropriate way to directly compare the safety and efficacy profiles of each formulation and dosage. TIOSPIR was specifically designed to be of an adequate size and duration that closely reflects the real-world COPD patient population.

TIOSPIR was a randomized, double-blind, double-dummy, event-driven, parallel-group study comparing the safety and efficacy of the once-daily COPD maintenance therapy, SPIRIVA, delivered via two devices: Respimat^®2.5 µg or 5 µg and HandiHaler^®18 µg. The large-scale trial included more than 17,000 patients randomized from more than 1,200 sites in 50 countries. The first primary endpoint was comparison of all-cause mortality (non-inferiority of the two Respimat^®treatment groups vs. HandiHaler^®). The second primary endpoint was a comparison of time to first exacerbation (superiority) between tiotropium Respimat^® 5 g once-daily and HandiHaler^®. A spirometry substudy evaluated the relative bronchodilator efficacy of the three arms in the study.

About Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder)
SPIRIVA HandiHaler is a prescription medicine used once every day (a maintenance medicine) to control symptoms of chronic obstructive pulmonary disease (COPD) by relaxing airways. COPD includes chronic bronchitis, emphysema or both.

SPIRIVA HandiHaler also reduces the likelihood of flare-ups (exacerbations), which are worsening of COPD symptoms (COPD exacerbations).

Important Safety Information for Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder)
Do not use SPIRIVA HandiHaler if you are allergic to tiotropium or ipratropium (e.g., Atrovent^®) or any of the ingredients in SPIRIVA. If your breathing suddenly worsens, your face, throat, lips or tongue swells, you get hives, itching or rash, stop taking SPIRIVA and seek immediate medical help.

SPIRIVA HandiHaler is not a rescue medicine and should not be used for treating sudden breathing problems.

Do not swallow SPIRIVA capsules. The contents of the capsule should only be inhaled through your mouth using the HandiHaler device.

If you have vision changes or eye pain or if you have difficulty passing urine or painful urination, stop taking SPIRIVA HandiHaler and call your doctor right away.

Tell your doctor if you have glaucoma, problems passing urine or an enlarged prostate, as these may worsen with SPIRIVA. Tell your doctor if you have kidney problems or are allergic to milk proteins. Ask your doctor if you are not sure. Also discuss with your doctor all the medicines you take, including eye drops.

The most common side effect with SPIRIVA is dry mouth. Others include constipation and trouble passing urine. For a complete list of reported side effects, ask your doctor or pharmacist.

Do not let the powder from the SPIRIVA capsule get into your eyes.

Dizziness and blurred vision may occur with SPIRIVA. Should you experience these symptoms, you should use caution when engaging in activities such as driving a car or operating appliances or other machines.

Read the Patient Information and the step-by-step Instructions for Use for SPIRIVA before you use your inhaler.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For full prescribing information, please visit www.spiriva.com, or call 1-800-542-6257 option #4.

Click here for full Spiriva Prescribing Information, Patient Information and Instructions for Use.

About COPD
Chronic obstructive pulmonary disease (COPD) is a term including chronic bronchitis and/or emphysema. This disease makes it harder to breathe because less air is able to flow in and out of the lungs. More than 26 million Americans may have COPD even those who haven't smoked in years and half of them remain undiagnosed. COPD is the third leading cause of death in the United States. It kills one person every four minutes and more people each year than breast cancer and diabetes combined.

Common symptoms of COPD include coughing, with or without mucus production, or shortness of breath. These symptoms are often confused with normal signs of aging. As COPD progresses, symptoms tend to get worse and more damage occurs in the lungs. Breathing gradually becomes more difficult until people with COPD feel like they are inhaling and exhaling through a small straw.

Leading respiratory forward
Through research, treatments and patient-centric support services, the Boehringer Ingelheim (BI) 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), BI 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.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.