Boehringer Ingelheim Presents Data for the Co-Administration of Two Approved Products for COPD Patients

RIDGEFIELD, Conn., October 27, 2014 – Boehringer Ingelheim today presented data from the ANHELTO^TM 1&2 studies (NCT01694771/NCT01696058) that evaluated the co-administration of Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder) (T) plus Striverdi^® Respimat^® (olodaterol) Inhalation Spray (O) inhaler in patients with chronic obstructive pulmonary disease (COPD).  The data were presented at the American College of Chest Physicians (ACCP) 80^th annual meeting (CHEST 2014) in Austin, Texas, and have also been published online this month in the International Journal of Chronic Obstructive Pulmonary Disease.

At Week 12, patients receiving T+O showed significant improvements in lung function, as measured by trough forced expiratory volume in one second (FEV₁) and FEV₁ area under the curve from 0-3 hours (FEV₁AUC_0-3h), compared to patients receiving tiotropium + placebo (T+P). 

“Doctors frequently use multiple products for maintenance treatment of COPD,” said lead study author Richard ZuWallack, MD, associate chief, Pulmonary Medicine, Saint Francis Hospital and Medical Center, Hartford, CT. “Dual bronchodilation has the potential to improve lung function more effectively in people living with COPD than treatment with a single bronchodilator.”

SPIRIVA HandiHaler is a once-daily long-acting muscarinic antagonist (LAMA) indicated for both the maintenance treatment of bronchospasm (narrowing of the airways) associated with COPD, including chronic bronchitis and emphysema, and to reduce COPD exacerbations.

STRIVERDI RESPIMAT is a once-daily long-acting beta agonist (LABA) indicated for the long-term maintenance bronchodilator treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. STRIVERDI RESPIMAT is not indicated to treat acute deteriorations of COPD and is not indicated to treat asthma. SPIRIVA HandiHaler delivers the medication as a powder and STRIVERDI RESPIMAT delivers olodaterol as a slow-moving mist.

ANHELTO^TM 1&2 were 12-week, replicate, double-blind studies in which COPD patients were randomized to receive tiotropium 18 μg once daily (via HandiHaler^®) + olodaterol 5 μg once daily (via Respimat^®) or tiotropium 18 μg once daily (via HandiHaler^®) + placebo (via Respimat^®). The ANHELTO^TM studies included more than 2,200 patients with COPD. The primary efficacy endpoints were change from baseline in trough FEV₁ and FEV₁AUC_0-3 after 12 weeks.

	ANHELTO-1	ANHELTO-2
	Mean Difference (T+O - T+P)
FEV1AUC0-3	117 mL (p<0.0001)	106 mL (p<0.0001)
Trough FEV1	62 mL (p<0.0001)	40 mL (p<0.0029)

The percentage of patients experiencing any adverse event (AE) in ANHELTO-1 was 45.3 percent with T+O 18/5 μg and 42.8 percent with tiotropium 18 μg. In ANHELTO-2, 40.1 percent of patients in the T+O 18/5 μg group experienced any AE, compared to 43.2 percent in the tiotropium 18 μg group. The most frequent adverse events across the two studies were worsening of COPD (10.7 percent) and dry mouth (2.7 percent).

“We are very encouraged by the data from the ANHELTO studies looking at the co-administration of two of our approved respiratory products, SPIRIVA HandiHaler and STRIVERDI RESPIMAT, for the maintenance treatment of COPD,” said Danny McBryan, MD, vice president, Clinical Development & Medical Affairs, Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc. “At Boehringer Ingelheim, we’re committed to exploring new treatment approaches so the approximately 15 million Americans who have been told by a healthcare provider that they have COPD can have more options.”

About Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder)

Indication
SPIRIVA HandiHaler is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, and for reducing COPD exacerbations.

Important Safety Informationfor Spiriva^® HandiHaler^®
Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder) is contraindicated in patients with a history of hypersensitivity to tiotropium, ipratropium (atropine derivatives) or any components of SPIRIVA capsules.

SPIRIVA HandiHaler is not indicated for the initial treatment of acute episodes of bronchospasm, i.e., rescue therapy.

Immediate hypersensitivity reactions, including urticaria, angioedema (swelling of lips, tongue or throat), rash, bronchospasm, anaphylaxis, or itching may occur after administration of SPIRIVA HandiHaler. Additionally, inhaled medicines, including SPIRIVA HandiHaler, may cause paradoxical bronchospasm. If any of these occurs, treatment with SPIRIVA HandiHaler should be stopped and other treatments considered.

Patients with a history of hypersensitivity reactions to atropine should be closely monitored for similar hypersensitivity reactions to SPIRIVA HandiHaler.

Use with caution in patients with severe hypersensitivity to milk proteins.

SPIRIVA HandiHaler should be used with caution in patients with narrow-angle glaucoma or urinary retention. Prescribers should instruct patients to consult a physician immediately should any signs or symptoms of narrow-angle glaucoma, or prostatic hyperplasia or bladder-neck obstruction occur.

Since dizziness and blurred vision may occur with the use of SPIRIVA HandiHaler, caution patients about engaging in activities such as driving a vehicle or operating appliances or machinery.

As SPIRIVA HandiHaler is a predominantly renally excreted drug, SPIRIVA HandiHaler use should be monitored closely in patients with moderate to severe renal impairment (creatinine clearance of ≤ 50 mL/min).

SPIRIVA HandiHaler has been used concomitantly with short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, and oral and inhaled steroids without increases in adverse drug reactions.

SPIRIVA HandiHaler may interact additively with concomitantly used anticholinergic medications. Avoid coadministration with other anticholinergic-containing drugs.

The most common adverse reactions (>5% incidence in the 1-year placebo controlled trials) reported with SPIRIVA HandiHaler (and placebo) were upper respiratory tract infection 41% (37%), dry mouth 16% (3%), sinusitis 11% (9%), pharyngitis 9% (7%), non-specific chest pain 7% (5%), urinary tract infection 7% (5%), dyspepsia 6% (5%), and rhinitis 6% (5%). In addition, the most common reported adverse reaction (>5% incidence) from the 4-year trial with SPIRIVA HandiHaler (and placebo) not included above was headache 6% (5%).

SPIRIVA capsules should not be swallowed and should only be inhaled through the mouth (oral inhalation) using the HandiHaler device. The HandiHaler device should not be used for administering other medications.

SPIRIVA capsules should always be stored in the sealed blisters, and only removed immediately before use, or else its effectiveness may be reduced.

Please see full Prescribing Information including Instructions for Use for SPIRIVA HandiHaler.

About Striverdi^® Respimat^® (olodaterol) Inhalation Spray

Indication
Striverdi^® Respimat^® (olodaterol) Inhalation Spray is a long-acting beta2-agonist indicated for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Important Limitations: STRIVERDI RESPIMAT is not indicated to treat acute deteriorations of COPD and is not indicated to treat asthma.

Important Safety Information for STRIVERDI RESPIMAT 

WARNING: ASTHMA-RELATED DEATH

Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large, placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including olodaterol, the active ingredient in STRIVERDI RESPIMAT. The safety and efficacy of STRIVERDI RESPIMAT in patients with asthma have not been established. STRIVERDI RESPIMAT is not indicated for the treatment of asthma.

All LABA are contraindicated in patients with asthma without use of a long-term asthma control medication.

STRIVERDI RESPIMAT should not be initiated in patients with acutely deteriorating COPD, which may be a life threatening condition, or used as rescue therapy for acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled short-acting beta2 agonist.

STRIVERDI RESPIMAT should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing long-acting beta₂ agonists as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

STRIVERDI RESPIMAT may produce paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs, STRIVERDI RESPIMAT should be discontinued immediately and alternative therapy instituted.

STRIVERDI RESPIMAT can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms, and should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, hypertrophic obstructive cardiomyopathy, and hypertension. If cardiovascular symptoms occur, STRIVERDI RESPIMAT may need to be discontinued. 

STRIVERDI RESPIMAT should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, in patients with known or suspected prolongation of the QT interval, and in patients who are unusually responsive to sympathomimetic amines.

Be alert to hypokalemia and hyperglycemia.

Immediate hypersensitivity reactions, including angioedema, may occur. If such a reaction occurs, therapy with STRIVERDI RESPIMAT should be stopped at once and alternative treatment should be considered.

The most commonly reported adverse reactions (≥2% incidence and more than placebo) with STRIVERDI RESPIMAT (and placebo) were nasopharyngitis, 11.3% (7.7%); upper respiratory tract infection, 8.2% (7.5%); bronchitis, 4.7% (3.6%); urinary tract infection, 2.5% (1.0%); cough, 4.2% (4.0%); dizziness, 2.3% (2.1%); rash, 2.2% (1.1%); diarrhea, 2.9% (2.5%); back pain, 3.5% (2.7%); and arthralgia 2.1% (0.8%).

STRIVERDI RESPIMAT should be used with extreme caution in patients treated with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated.

STRIVERDI RESPIMAT should be used with caution in patients treated with additional adrenergic drugs, non‐potassium-sparing diuretics, and beta‐blockers.

STRIVERDI RESPIMAT is for oral inhalation only.

Please see full Prescribing Information, including boxed WARNING, Medication Guide, and Instructions for Use for STRIVERDI RESPIMAT.

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.

About COPD
Chronic obstructive pulmonary disease (COPD) is a term including 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. 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.

Leading Respiratory Forward
Through research, Boehringer Ingelheim (BI) has developed drug therapies to help patients with lung diseases. 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 help patients with COPD, asthma, lung cancer, and idiopathic pulmonary fibrosis.

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 142 affiliates and more than 47,400 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.

Social responsibility is a central element of Boehringer Ingelheim's culture. 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 2013, Boehringer Ingelheim achieved net sales of about $18.7 billion (14.1 billion euro). R&D expenditure in the Prescription Medicines business corresponds to 19.5% of its net sales.

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

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