Value through Innovation23 July 2014
03 September 2012

New data show significant improvements in lung function using combination of tiotropium and olodaterol* in COPD patients

•   Boehringer Ingelheim is currently developing a once-daily fixed-dose
    combination of its investigational LABA olodaterol and its well established 
    LAMA tiotropium

•   The TOviTO® Phase III clinical trial programme is already underway to fully
    evaluate the potential of this combination

Ingelheim, Germany, 3rd September, 2012 – New phase II data presented for the first time today at the 2012 European Respiratory Society (ERS) congress show that combining tiotropium with olodaterol significantly improved lung function (FEV1) over 24 hours in COPD patients compared to olodaterol alone.1

Significant improvements were seen for all combinations of doses tested (tiotropium 1.25, 2.5 and 5 μg / olodaterol 5 μg, 10 μg) compared with the respective olodaterol monotherapies.1 Both treatments were administered using the patient-preferred2-5 Respimat® Soft MistTM Inhaler (SMI) device.

After 4 weeks of treatment, the combination of tiotropium and olodaterol provided an average lung function improvement compared to the pre-treatment baseline of up to 342 mL over the first 6 hours (FEV1 AUC0-6) and improvements in trough FEV1 of up to 166 mL.

Compared to olodaterol monotherapy, the combination of tiotropium and olodaterol further increased lung function by up to 144 mL (FEV1 AUC0-6) and 84 mL (trough FEV1).

The new study completes a comprehensive Phase II programme initiated by Boehringer Ingelheim that thoroughly investigated different doses of each active component to identify the optimal doses for the fixed-dose combination.

Dr. René Aalbers of the Department of Pulmonology, Martini Hospital, Groningen, Netherlands

Dr. René Aalbers

Dr. René Aalbers of the Department of Pulmonology, Martini Hospital, Groningen, Netherlands, and lead author of the study said: "Combining two long-acting bronchodilators with different modes of action - the well established once-daily LAMA§ tiotropium with olodaterol, an investigational and promising once-daily LABA** with a convincing 24-hour profile - has a complementary effect in the treatment of COPD patients. Olodaterol is an ideal partner to tiotropium due to its similar long-lasting effect at a low dose."

The new data are from a Phase II dose-finding study: a randomised, double-blind, 4-period, incomplete crossover trial of 4 weeks duration involving 232 COPD patients with post-bronchodilator FEV1 of ≥30% and <80% of predicted normal.

To assist in the development of the fixed dose combination, various doses of tiotropium (1.25, 2.5 and 5 μg) were tested in combination with either olodaterol 5 μg or 10 μg and efficacy measured against the respective doses of olodaterol as monotherapy.

The study compared pre-dose (trough) lung function and lung function up to 6 hours post-dose after 4 weeks treatment with tiotropium and olodaterol as a free combination versus olodaterol as a monotherapy.

The mono components and all combination doses showed a favourable safety profile.

Comprehensive Phase III programme TOviTO® ongoing
The TOviTO® programme, one of the largest global Phase III clinical trial programmes ever conducted in COPD, is already underway to fully evaluate the potential benefits of tiotropium and olodaterol in a once-daily fixed-dose combination using Respimat® SMITM in the treatment of patients with COPD. It consists of several Phase III studies including the two pivotal registration trials TOnado 1&2, which are multi-centred, multi-national, randomised, double-blind, parallel group studies randomising a total of 5,000 COPD patients across the spectrum of disease severity from GOLD Stage II to GOLD Stage IV at more than 500 trial sites in approximately 40 countries.

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

Professor Klaus Dugi

In addition to evaluating the effects of tiotropium + olodaterol FDC on lung function, the TOviTO® programme is also focussed on the evaluation of other important clinical outcomes that reflect the daily life of patients with COPD.

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: "Olodaterol, a once-daily LABA with a proven 24-hour profile in patients with COPD, has been designed by Boehringer Ingelheim as an ideal combination partner for tiotropium, the first once-daily inhaled long-acting anticholinergic bronchodilator to provide 24-hour bronchodilation in COPD. These new data give us confidence that we are moving closer to the fixed dose combination product of tiotropium and olodaterol, which could become a new treatment option for patients with COPD."

European Respiratory Society Annual Congress 2012 Boehringer Ingelheim tiotropium and olodaterol in COPD data

Abstract title: Dose-finding study for tiotropium and olodaterol when administered in combination via the Respimat® inhaler in patients with COPD
Poster number: P2882
Session: A5, Session 314, 14:45-16:45, Monday, 03 September 2012

The Boehringer Ingelheim NewsHome: An innovative resource for journalists
www.NewsHome.com is THE site to discover more about Boehringer Ingelheim’s investigational compounds in respiratory and beyond. With a focus on Asthma, COPD and Idiopathic Pulmonary Fibrosis, the NewsHome contains Boehringer Ingelheim press releases, disease backgrounders, and other relevant materials like filmed expert opinion.

About COPD
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death and disability throughout the world, and has a significant physical and emotional impact on those who suffer from the disease.6

As COPD progresses, lung function declines and physical activity may become severely limited, disrupting the patient’s ability to lead a full life, interfering with everyday tasks and participation in family routines.7 This can lead to people feeling afraid, anxious, frustrated, isolated and depressed.8

World Health Organisation (WHO) figures estimated that 65 million people were living with COPD.9 According to WHO more than 3 million people died of COPD in 2005, which corresponds to 5% of all deaths globally.9 However, mortality data is likely to be significantly under-estimated due to under-recognition and under-diagnosis of COPD.7 WHO predicts that COPD will become the third leading cause of death worldwide by 2030.10

COPD patients often have other serious medical conditions, such as heart disease, diabetes, osteoporosis and depression - making treatment of COPD in parallel with these diseases even more difficult.11 Due to the chronic nature of the disease and its disabling symptoms, COPD can also represent a considerable burden on those who care for friends and relatives with the condition. Early diagnosis and intervention with appropriate treatment following an exacerbation is important to help patients recover more rapidly and improve their quality of life.12


About Olodaterol
Olodaterol is a once-daily, long-acting beta2-agonist (LABA) bronchodilator with a proven 24-hour profile in patients with COPD. Olodaterol significantly improves lung function (FEV1) over at least 24 hours. Olodaterol has been designed by Boehringer Ingelheim as an ideal combination partner for tiotropium for the maintenance treatment of COPD. The company is currently studying the efficacy of a once-daily fixed-dose combination of tiotropium and olodaterol in the TOviTO® Phase III trial programme.


About Tiotropium
Tiotropium has been marketed under the brand name Spiriva® for ten years. It is the most prescribed COPD therapy worldwide and has a well established efficacy and safety profile, supported by data from 175 clinical trials. Tiotropium was the first inhaled once-daily anticholinergic (LAMA) to provide 24-hour bronchodilation in COPD.


About Respimat® Soft MistTM Inhaler
Developed by Boehringer Ingelheim, Respimat® Soft MistTM Inhaler (SMI) is a new generation inhaler with a unique delivery mechanism, which is preferred by patients compared to other currently available inhalers.2-5 Respimat® produces a long-lasting, slow moving Soft MistTM13,14 that is easy to inhale.15


Boehringer Ingelheim: Leading respiratory forward
The treatment of respiratory diseases has been a major area of focus for Boehringer Ingelheim for over 90 years and significant resources are dedicated to research in this therapy area.

Boehringer Ingelheim has a long heritage in the field of respiratory diseases, and developed Spiriva®, which is currently the most investigated and most prescribed maintenance prescription medicine for COPD. Boehringer Ingelheim has also branched out into developing treatment options for other airway diseases, including asthma, lung cancer and idiopathic pulmonary fibrosis.


Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 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 pledges to be socially responsible. 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 endeavours.

In 2011, Boehringer Ingelheim achieved net sales of about €13.17 billion. R&D expenditure in the business area Prescription Medicines corresponds to 23.5% of its net sales.

References
1 Aalbers R, Maleki-Yazdi MR, Hamilton A, et al. Dose-finding study for tiotropium and olodaterol when administered in combination via the Respimat® inhaler in patients with COPD. ERS 2012 abstract P2882.
2 Brand P et al. Respimat® Soft MistTM inhaler preferred to Diskus® by Patients with COPD and /or Asthma. J Aerosol Med 2007; 20(2): 165.
3 Hodder R, Price D. Patient Preference for Inhaler Devices in Chronic Obstructive Pulmonary Disease: Experience with Respimat® Soft MistTM Inhaler. Int J Chronic Obstruct Pulm Dis 2009; 4: 381-390.
4 Hodder R, Reese PR, Slaton T. Asthma Patients Prefer Respimat® Soft MistTM Inhaler to Turbohaler. Int J Chronic Obstruct Pulm Dis 2009; 4: 225-232.
5 Schuermann W, Schmidtmann S, Moroni P, et al. Respimat® Soft MistTM Inhaler versus hydrofluroalkane metered dose inhaler: patient preference and satisfaction. Treatm Respir Med 2005;4 : 53-61.
6 Confronting COPD in America: Executive Summary. New York, NY: Schulman, Ronca, and Bucuvalas Inc; 2001: 1-20.
7 From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. Available from: http://www.goldcopd.org/.
8 Maurer J , Rebbapragada B, Borsen S. et al. Anxiety and depression in COPD. Chest 2008; 134: 43S-56S.
9 http://www.who.int/respiratory/copd/burden/en/index.html [accessed 20/06/12].
10 http://www.who.int/respiratory/copd/en/ [accessed 20/06/12].
11 Yawn BP, Kaplan A. Co-morbidities in people with COPD: a result of multiple diseases, or multiple manifestations of smoking and reactive inflammation? Prim Care Respir J 2008;17 (4):199-205
12 Wilkinson TMA, Donaldson GC, Hurst JR et al. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 169: 1298-1303.
13 Dhand R. Aerosol Plumes: Slow and Steady Wins The Race. J Aerosol Med 2005; 18(3): 261-63.
14 Hochrainer D, Hölz H. Comparison of Aerosol Velocity and Spray Duration of Respimat® Soft MistTM Inhaler and Pressurized Metered Dose Inhalers. J Aerosol Med 2005; 18(3): 273-282.
15 Freytag F, Golisch W, Wolf K. New soft mist inhaler is effective and easy to use in patients with asthma and COPD. Eur Respir J 2005; 26 (Suppl 49): 338s.

*   The combination of tiotropium and olodaterol is not licensed for the treatment of COPD
   FEV1 is Forced Expiratory Volume in one second
‡   Trough FEV1 is Forced Expiratory Volume in one second at the end of the dosing interval (at approximately 24 hours post-treatment administration)

§   Long-acting muscarinic antagonist
**  Long-acting beta2-agonist

Media contact

  • Sebastian Wachtarz
    Boehringer Ingelheim

    Corporate Communications
    Sebastian Wachtarz
    Binger Strasse 173
    55216 Ingelheim am Rhein

    GERMANY

Media contact

  • Sebastian Wachtarz
    Boehringer Ingelheim

    Corporate Communications
    Sebastian Wachtarz
    Binger Strasse 173
    55216 Ingelheim am Rhein

    GERMANY

Dr. René Aalbers

Dr. Ren&#233; Aalbers of the Department of Pulmonology, Martini Hospital, Groningen, Netherlands

Combining olodaterol and tiotropium in COPD

(WMV)

Prof. Klaus Dugi

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim

Olodaterol as the ideal combination partner for tiotropium in COPD

(WMV)