Olodaterol Shows Sustained Improvements in Lung Function in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Ridgefield, CT, September 8, 2013 – Data from the olodaterol Phase 3 clinical program, presented for the first time at the European Respiratory Society (ERS) Annual Congress 2013 in Barcelona, showed the addition of olodaterol 5 and 10 µg delivered once daily via the Respimat^® inhaler provided improvements in lung function in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Olodaterol is an investigational long-acting beta agonist (LABA) currently being studied as a once-daily maintenance bronchodilator treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.

These data are from two sets of replicate, 48-week pivotal studies evaluating the long-term efficacy and safety of once-daily olodaterol in 5 and 10 µg doses, as well as two sets of replicate, 6-week studies investigating olodaterol’s 24-hour bronchodilation profile. In an effort to more accurately represent the clinical practice setting, patients involved in the Phase 3 program were allowed to continue their usual care, with the exception of LABAs. Usual care included long- and short-acting anticholinergics, short-acting beta agonists, inhaled corticosteroids (ICS) and xanthines.

“Despite advances in the treatment of COPD, there remains a significant need to reduce the burden of COPD on patients’ lives,” said lead study author Gary T. Ferguson, MD, of the Pulmonary Research Institute of Southeast Michigan, Livonia, Michigan. “We are excited about these data because we see that the lung function improvements shown with olodaterol may translate into patient-related benefits over and above those seen with usual care, and these improvements on top of permitted bronchodilator therapies makes these positive results even more noteworthy.”

Of the more than 20 presentations from the Boehringer Ingelheim lung health portfolio being presented at this year’s ERS Congress, five are from the Phase 3 olodaterol clinical program.

“We are encouraged by these findings and have an ongoing commitment to bringing new treatment options to patients with COPD,” said Tunde Otulana, MD, senior vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “Our leadership role in lung health is driven by our heritage and passion for finding ways to address the unmet needs of the millions of Americans living with debilitating lung diseases such as COPD.”

Key Results from the 48-Week Phase 3 Olodaterol Studies
In one set of 48-week Phase 3 pivotal studies (NCT00782210 and NCT00782509), olodaterol 5 and 10 µg delivered once daily via the Respimat^® inhaler provided statistically significant improvements in lung function, as measured by FEV₁, versus placebo plus usual care in patients with moderate to very severe COPD (P < 0.05; n=613 and 635). 

	Study 1		Study 2
	Adjusted mean FEV1 AUC0-3 difference from placebo	Adjusted mean trough FEV1 difference from placebo	Adjusted mean FEV1 AUC0-3 difference from placebo	Adjusted mean trough FEV1 difference from placebo
Olodaterol 5 µg	0.172 L (P < 0.0001)	0.091 L (P < 0.0001)	0.151 L (P < 0.0001)	0.047 L (P < 0.05)
Olodaterol 10 µg	0.176 L (P < 0.0001)	0.101 L (P < 0.0001)	0.143 L (P < 0.0001)	0.048 L (P < 0.01)

In a second set of 48-week studies (NCT00793624 and NCT00796653), the same dose and delivery of olodaterol provided comparable improvements in lung function compared to 12 µg formoterol twice daily in these COPD patients (n=904 and 934). After 24 weeks of treatment, both doses of olodaterol and formoterol provided statistically significant improvements in FEV₁ AUC_0-3.

	Study 1		Study 2
	Adjusted mean FEV1 AUC0-3 difference from placebo	Adjusted mean trough FEV1 difference from placebo	Adjusted mean FEV1 AUC0-3 difference from placebo	Adjusted mean trough FEV1 difference from placebo
Olodaterol 5 µg	0.15 L (P < 0.0001)	0.08 L (P < 0.001)	0.13 L (P < 0.0001)	0.05 L (P < 0.01)
Olodaterol 10 µg	0.17 L (P < 0.0001)	0.09 L (P < 0.0001)	0.15 L (P < 0.0001)	0.07 L (P < 0.001)
Formoterol 12 µg	0.18 L (P < 0.0001)	0.05 L (P < 0.01)	0.15 L (P < 0.0001)	0.04 L (P < 0.05)

Olodaterol 5 µg was shown to provide significant improvement (P < 0.0001) in lung function within five minutes following the first dose.

In addition, COPD patients had less need for both day- and night-time rescue medication when using both doses of olodaterol (5 and 10 µg) delivered once daily via the Respimat^® inhaler and formoterol versus placebo over the 48-week treatment period (P < 0.01).

In these studies, there was no significant difference in adverse events between the olodaterol treatment arm and the control arm with 71.0 percent of patients receiving olodaterol 5 µg reporting an adverse event compared to 72.7 percent of patients receiving olodaterol 10 µg, 70.8 percent of patients receiving placebo and 69.1 percent of patients receiving formoterol 12 µg. The most common adverse reactions were nasopharyngitis, dizziness, rash and arthralgia.

Key Results from the 6-Week Phase 3 Olodaterol Studies
In the two replicate, randomized, double-blind, placebo-controlled crossover studies, patients received olodaterol 5 µg and 10 µg delivered once daily via the Respimat^® inhaler, tiotropium 18 µg once daily via the HandiHaler^® or placebo in addition to usual care (ICS and xanthines) for 6 weeks (n=108 and 122).

The data presented at ERS showed that the improvements seen in lung function with olodaterol, as measured by FEV₁ responses, were maintained over 24 hours (P < 0.001): 

	Study 1		Study 2
	FEV1 AUC0-12 response	FEV1 AUC12–24 response	FEV1 AUC0-12 response	FEV1 AUC12–24 response
Olodaterol 5 µg	0.185 L (P < 0.0001)	0.131 L (P < 0.0001)	0.197 L (P < 0.0001)	0.153 L (P < 0.0001)
Olodaterol 10 µg	0.207 L (P < 0.0001)	0.178 L (P < 0.0001)	0.221 L (P < 0.0001)	0.170 L (P < 0.0001)
Tiotropium 18 μg	0.173 L (P < 0.0001)	0.123 L (P < 0.0001)	0.221 L (P < 0.0001)	0.164 L (P < 0.0001)

In these studies, there was no significant difference in adverse events between the olodaterol treatment arm and the placebo arm.

Reported Adverse Events - Study 1:

• Olodaterol 5 µg: 31.7 percent
• Olodaterol 10 µg: 33.7 percent
• Placebo: 34.3 percent

Reported Adverse Events - Study 2:

• Olodaterol 5 µg: 35.7 percent
• Olodaterol 10 µg: 38.9 percent
• Placebo: 33.9 percent

The most common adverse reactions were nasopharyngitis, COPD, cough and dyspnea. 

About the Olodaterol Phase 3 Clinical Program
Olodaterol’s efficacy as a once-daily bronchodilator in patients with COPD is being investigated in a robust clinical trial program, involving more than 3,500 patients with moderate to very severe COPD (stages II, III and IV as defined by the Global Initiative for Chronic Obstructive Lung Disease [GOLD]).

Olodaterol is being investigated to determine the medicine’s efficacy in treating COPD patients and is not currently approved for this indication.

About COPD
Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema. This disease makes it harder to breathe because less air is able to flow in and out of the lungs. As many as 26 million Americans may have COPD – even those who haven't smoked in years – and nearly half of them remain undiagnosed. COPD is the third leading cause of death in the United States. It kills one person every four minutes in the United States.

Common symptoms of COPD include shortness of breath and coughing with or without excess mucus.

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

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