Boehringer Ingelheim Announces U.S. Filing Acceptance of New Drug Application for Spiriva® Respimat® (tiotropium bromide) Inhalation Spray for the Treatment of Asthma

RIDGEFIELD, Conn., Nov. 3, 2014 /PRNewswire/ -- Boehringer Ingelheim today announced that the U.S. Food and Drug Administration (FDA) accepted for review the New Drug Application (NDA) for Spiriva^® Respimat^® (tiotropium bromide) Inhalation Spray for the long-term, once-daily, add-on maintenance treatment of asthma in patients 12 years of age and older who remain symptomatic on at least inhaled corticosteroids (ICS). SPIRIVA RESPIMAT is a long-acting muscarinic antagonist (LAMA) currently being studied to determine its efficacy and safety in treating asthma patients and is not currently approved for this indication.

SPIRIVA RESPIMAT is approved for the maintenance treatment of bronchospasm (narrowing of the airways) associated with chronic obstructive pulmonary disease (COPD) and to reduce COPD exacerbations.

"Boehringer Ingelheim is committed to addressing the unmet medical needs of patients with a variety of respiratory conditions. We look forward to further discussions with the FDA about the potential use of SPIRIVA RESPIMAT in asthma," said Sabine Luik, MD, senior vice president, Medicine & Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.

The NDA submission package for tiotropium in asthma is based on data from the UniTinA-asthma^® clinical trial program, including data from the pivotal PrimoTinA- (NCT00772538/NCT00776984), MezzoTinA- (NCT01172808/NCT01172821) and RubaTinA-asthma^® (NCT01257230) studies, which evaluated tiotropium delivered via the Respimat^® inhaler as add-on treatment for adults and adolescents with moderate to severe asthma who continued to experience symptoms despite maintenance treatment with at least ICS. These studies are part of the Company's comprehensive Phase III UniTinA-asthma^® clinical trial program, which includes several studies investigating tiotropium in asthma patients across a range of ages and disease severities. The UniTinA-asthma^® program includes more than 6,000 adult, adolescent and pediatric asthma patients in more than 150 sites globally.

Tiotropium has been available in the U.S. for more than ten years for the maintenance treatment of COPD under the brand name Spiriva^® HandiHaler^® (tiotropium bromide inhalation powder). The FDA approved SPIRIVA RESPIMAT for the treatment of COPD in September 2014. SPIRIVA RESPIMAT provides a pre-measured amount of medicine in a slow-moving mist that helps patients inhale the medicine. The Respimat^® inhaler was developed to actively deliver medication in a way that does not depend on how fast air is breathed in from the inhaler.

About Spiriva^® Respimat^® (tiotropium bromide) Inhalation Spray

Indication
SPIRIVA^® RESPIMAT^® (tiotropium bromide) Inhalation Spray 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 Information for SPIRIVA RESPIMAT
SPIRIVA RESPIMAT is contraindicated in patients with a hypersensitivity to tiotropium, ipratropium, or any component of this product. Immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported.

SPIRIVA RESPIMAT is intended as a once-daily maintenance treatment for COPD and should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm.

Immediate hypersensitivity reactions, including urticaria, angioedema (including swelling of the lips, tongue or throat), rash, bronchospasm, anaphylaxis, or itching may occur after administration of SPIRIVA RESPIMAT. If such a reaction occurs, discontinue SPIRIVA RESPIMAT at once and consider alternative treatments. Given the similar structural formula of atropine to tiotropium, patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to SPIRIVA RESPIMAT.

Inhaled medicines, including SPIRIVA RESPIMAT, may cause paradoxical bronchospasm. If this occurs, it should be treated with an inhaled short-acting beta2-agonist such as albuterol. Treatment with SPIRIVA RESPIMAT should be stopped and other treatments considered.

SPIRIVA RESPIMAT should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

SPIRIVA RESPIMAT should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with SPIRIVA RESPIMAT should be monitored closely for anticholinergic side effects.

The most common adverse reactions (>3% incidence in the placebo-controlled trials with treatment durations of between 4 and 48 weeks) with SPIRIVA RESPIMAT (and placebo) were pharyngitis 12% (10%), cough 6% (6%), dry mouth 4% (2%), and sinusitis 3% (3%).

SPIRIVA RESPIMAT may interact additively with concomitantly used anticholinergic medications. Avoid administration of SPIRIVA RESPIMAT with other anticholinergic-containing drugs.

Inform patients not to spray SPIRIVA RESPIMAT into the eyes.

Click here for full SPIRIVA RESPIMAT Prescribing Information, including Instructions for Use.

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 Information for 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.

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 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.

Although asthma cannot be cured, appropriate management can control the disease in many patients. Despite current treatment options, approximately 40 percent of patients with asthma remain symptomatic.

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

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

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