New Data: STIOLTO^® RESPIMAT^® (tiotropium bromide+olodaterol) Inhalation Spray Significantly Improved Exercise Capacity in People with COPD

RIDGEFIELD, Conn., September 5, 2016 – Boehringer Ingelheim today announced the first results from the Phase IIIb/IV PHYSACTO trial that showed STIOLTO RESPIMAT, combined with exercise training, helps people with COPD walk for longer periods of time compared to those receiving placebo. All participants of the trial were also enrolled in a self-management behavior modification program, which provided health education and skills to help better manage COPD. These data were presented today at the European Respiratory Society (ERS) International Congress 2016 in London.

In the PHYSACTO trial, exercise capacity was measured by the length of time people with COPD could walk in an Endurance Shuttle Walking Test, which measures how far someone can walk at a standard speed without stopping for a rest.

After 8 weeks, in the tiotropium+olodaterol RESPIMAT combined with exercise training arm, exercise capacity in people with moderate-to-severe COPD significantly increased by 45.8 percent (p<0.001), compared to those receiving placebo with no exercise training (356 vs. 244 seconds respectively). Furthermore, tiotropium+olodaterol RESPIMAT was shown to reduce shortness of breath (also known as dyspnea) associated with physical activity, compared to placebo.

Long-acting beta2-adrenergic agonists, such as olodaterol, one of the active ingredients in STIOLTO RESPIMAT, increase the risk of asthma-related death. STIOLTO RESPIMAT is not indicated for asthma and should not be initiated in acutely deteriorating COPD patients or for the relief of acute symptoms. STIOLTO RESPIMAT is contraindicated in patients with a hypersensitivity to tiotropium, ipratropium, olodaterol, or any component of this product. As with other inhaled medicines, STIOLTO RESPIMAT may cause paradoxical bronchospasm that may be life-threatening. The most common adverse reactions were nasopharyngitis, cough and back pain.

Please see complete Important Safety Information below.

“It is vital for people with COPD to stay active as this may help slow the progression of disease burden,” said study investigator Professor Thierry Troosters, Head, Research Group for Cardiovascular and Respiratory Rehabilitation, University of Leuven, Belgium. “This new study is the first to demonstrate that a holistic approach to COPD management, which includes behavior modification enriched with exercise training and effective long acting bronchodilator therapy, can improve exercise capacity and reduce shortness of breath.”

Additional PHYSACTO results showed that even without exercise training, there was a significant improvement in exercise capacity in the tiotropium+olodaterol RESPIMAT arm (29.2 percent increase in shuttle walk duration; p<0.05), compared to placebo (315 vs. 244 seconds respectively).

COPD is a serious but manageable lung disease. Even in the early stages of COPD, people may experience breathlessness during daily activities. To avoid shortness of breath, people with COPD often reduce the amount of physical activity they undertake and do less of their daily activities. This reduction in physical activities has a significant negative impact on their quality of life and can lead to their condition worsening.

The PHYSACTO trial (NCT02085161) was designed to assess the effect of COPD maintenance therapy alone or in combination with supervised exercise training on exercise capacity and physical activity outcomes, including the amount of physical activity (as measured by an activity monitor) and perceived difficulties (as measured by the Functional Performance Inventory-Short Form score).

The participants of the PHYSACTO trial were randomized into groups, which received either tiotropium+olodaterol RESPIMAT with and without exercise training, tiotropium alone, or placebo. A 12-week self-management behavior modification program was included for all four groups to provide an optimal environment for translating improvements in exercise capacity into increases in daily activity. The self-management behavior modification program included strategies for participants to help them exercise, including a pedometer (a device to count steps), and education to support their COPD management plan.

These new data build on results from the MORACTO^® and TORRACTO^® 1&2 studies that showed tiotropium+olodaterol RESPIMAT significantly improved exercise endurance time vs. placebo. The PHYSACTO trial is part of the large-scale TOviTO^® Phase III clinical trial program, investigating the efficacy and safety of tiotropium+olodaterol RESPIMAT in COPD.

About the RESPIMAT Inhaler
RESPIMAT, the platform inhaler for the Boehringer Ingelheim respiratory therapies, was designed to get medicine deep into patients’ lungs as a slow-moving mist. The slow moving mist of the RESPIMAT inhaler provides patients with enough time to breathe in the medication. The RESPIMAT inhaler operates independent of inspiratory effort, helping patients effectively breathe the medicine into their lungs while minimizing inhalation effort.

As with all inhaled drugs, the actual amount of drug delivered to the lung may depend on patient factors, such as coordination between actuation of the inhaler and inspiration through the delivery system. The duration of inhalation should be at least as long as the spray duration (1.5 seconds).

Boehringer Ingelheim’s RESPIMAT family of products includes four FDA-approved medicines for COPD and asthma.

About COPD
Chronic obstructive pulmonary disease (COPD) is a term that includes chronic bronchitis and/or emphysema. This disease can make breathing harder because less air is able to flow in and out of the lungs. Chronic lower respiratory diseases, which include COPD, are the third leading cause of death in the United States, and approximately 15 million Americans have been told by a healthcare provider that they have COPD.

The most common symptom of COPD is shortness of breath, especially with physical activities. Coughing, with or without mucus production, is also a common symptom of COPD. These symptoms can be misunderstood as signs of aging. COPD is usually associated with progressive airway damage and loss that cause breathing to get more difficult.

INDICATION for STIOLTO RESPIMAT
STIOLTO RESPIMAT (tiotropium bromide and olodaterol) Inhalation Spray is a prescription medicine used long term, two puffs once each day, in controlling symptoms in adults with chronic obstructive pulmonary disease (COPD). COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both.

STIOLTO contains the anticholinergic, tiotropium, and the long-acting beta2-adrenergic agonist (LABA), olodaterol.  STIOLTO works by helping the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath.

STIOLTO is not for treating sudden symptoms of COPD. Always have a rescue medicine with you to treat sudden symptoms. If you do not have a rescue inhaler, contact your healthcare provider to have one prescribed for you.

Do not use STIOLTO if you have asthma. STIOLTO is approved to treat COPD only.

IMPORTANT SAFETY INFORMATION
People with asthma who take long-acting beta2-agonist (LABA) medicines, such as olodaterol, (one of the medicines in STIOLTO), have an increased risk of death from asthma problems. It is not known if LABA medicines, such as olodaterol (one of the medicines in STIOLTO), increase the risk of death in people with COPD. STIOLTO has been approved for chronic obstructive pulmonary disease (COPD) only. STIOLTO is NOT to be used in asthma.

Do not use STIOLTO if you are allergic to tiotropium, ipratropium, atropine or similar drugs, olodaterol, or any ingredient in STIOLTO. Symptoms of a serious allergic reaction may include rash, hives, swelling of the face, mouth, and tongue, and breathing problems.  Call your healthcare provider or get emergency medical care if you get any symptoms of a serious allergic reaction. Do not use STIOLTO for treating sudden breathing problems.  Always have a rescue inhaler with you to treat sudden symptoms.

Do not use STIOLTO more often or at higher doses than prescribed by your doctor. Do not use STIOLTO with other LABAs or anticholinergics. Get emergency medical care if your breathing problems worsen quickly or if you use your rescue inhaler but it does not relieve your breathing problems. Call your healthcare provider if breathing problems worsen over time while using STIOLTO.

Tell your doctor about all your medical conditions including heart problems, high blood pressure, seizures, thyroid problems, diabetes, kidney problems, glaucoma, enlarged prostate, and problems passing urine.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines (including eye drops), vitamins, and herbal supplements. STIOLTO may interact with other medicines which may cause serious side effects.

STIOLTO can cause serious side effects, including sudden shortness of breath that may be life threatening, fast or irregular heartbeat, increased blood pressure, chest pain, high blood sugar, or low blood potassium that may cause muscle spasms or weakness or abnormal heart rhythm. If any of these happens, stop taking STIOLTO and seek immediate medical help.

STIOLTO can cause new or worsening eye problems including narrow-angle glaucoma, and can increase the pressure in your eyes, which can cause the following symptoms: eye pain, blurred vision, seeing halos or colored images along with red eyes. If you have any of these symptoms, stop taking your medicine and call your doctor right away.

STIOLTO can cause new or worsened urinary retention.  Symptoms of urinary retention may include difficulty passing urine, painful urination, urinating frequently, or urinating in a weak stream or drips. If you have any of these symptoms, stop taking your medicine and call your doctor right away.

STIOLTO is for oral inhalation only. The STIOLTO cartridge is only intended for use with the STIOLTO RESPIMAT inhaler.

Do not spray STIOLTO into your eyes.

The most common side effects of STIOLTO are runny nose, cough, and back pain.

Tell your healthcare provider about any side effect that bothers you or that does not go away.

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.

Read the step-by-step patient Instructions for Use for STIOLTO RESPIMAT before you use your inhaler.

Please see accompanying Medication Guide, Instructions for Use, and Full Prescribing Information, including boxed WARNING.

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with 145 affiliates and more than 47,000 employees. Since its founding in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel treatments for human and veterinary medicine.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and their families. Our employees create and engage in programs that strengthen our communities. To learn more about how we make more health for more people, visit our Corporate Social Responsibility Report.

In 2015, Boehringer Ingelheim achieved net sales of about $15.8 billion (14.8 billion euros). R&D expenditure corresponds to 20.3 percent of its net sales.

For more information please visit www.us.boehringer-ingelheim.com, or follow us on Twitter @BoehringerUS.

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