Value through Innovation31 August 2014
21 May 2012

Boehringer Ingelheim’s once-daily bronchodilator olodaterol* successfully completes Phase II clinical trial program in COPD

  • Olodaterol significantly improved lung function (FEV1) for at least 24 hours compared to placebo
  • Strong efficacy results achieved with the comparably low once-daily QD 5µg dose and a favourable safety profile
  • Boehringer Ingelheim is designing and developing olodaterol as a once-daily COPD maintenance treatment to partner with tiotropium

Ingelheim, Germany, May 21, 2012 – Data presented today at the 2012 Annual Meeting of the American Thoracic Society completes the olodaterol monotherapy Phase II clinical trial program in patients with chronic obstructive pulmonary disease (COPD). This Phase II study compared the efficacy of once-daily versus twice-daily olodaterol, delivered via the Respimat® Soft Mist™ Inhaler (SMI) device.

Olodaterol is a once-daily, long-acting ß2-agonist (LABA) that Boehringer Ingelheim is designing and developing as a COPD maintenance treatment to partner with tiotropium. Olodaterol monotherapy and the fixed-dose combination (FDC) with tiotropium are being developed in the Respimat® SMI. Olodaterol’s efficacy as a true once-daily bronchodilator was investigated in a large Phase II clinical trial program, which demonstrated a significant improvement in lung function for at least 24 hours in patients with COPD.1,2 The Phase III trials have also been completed and will be presented at future medical meetings.

The most recently presented Phase II randomised, double-blind, cross-over study demonstrated a statistically significant increase in the lung function parameter FEV1 for at least 24 hours with a once-daily (QD) 5 µg dose of olodaterol which was as pronounced as that observed with a QD 10 µg dose. Overall, the QD 5 µg dose of olodaterol offered a superior 24-hour profile to both the QD 10 µg and twice-daily 2 µg doses.3 These results were comparable to previous Phase II studies which demonstrated that all dosages of olodaterol provided significantly greater bronchodilation (FEV1) for at least 24 hours, compared to placebo.1,2 Olodaterol was well tolerated in all dosages tested, with no relationship of total daily dose to the overall incidence of adverse events.1,2,3

Professor Guy Joos

Professor Guy Joos, Head of the Department of Respiratory Diseases, at Ghent University Hospital, Belgium

Professor Guy Joos, Head of the Department of Respiratory Diseases, at Ghent University Hospital, Belgium, and the co-ordinating investigator for the trial, said: “In this study, olodaterol was shown to be a true once-daily LABA providing 24-hour bronchodilation in COPD patients. It is promising to see that the strong efficacy results of the Phase II programme were achieved with the comparably low QD 5µg dose and a favourable safety profile.”

The future combination partner to olodaterol, tiotropium, is a long-acting anticholinergic drug (long-acting muscarinic antagonist/LAMA) that provides 24-hour bronchodilation.4 It is being marketed under the brand name Spiriva® in COPD. Spiriva® HandiHaler® is the most investigated and prescribed maintenance COPD drug worldwide.25

Professor Klaus Dugi

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

Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim, said: “Boehringer Ingelheim is committed to advancing respiratory research and treatment. Our ultimate goal is to provide physicians and patients with a very efficient once-daily LAMA/LABA fixed-dose combination through a proficient drug delivery system, the Respimat® Soft Mist™ Inhaler. We are leading the field in the endeavour to achieve this, being the company that brought tiotropium to patients worldwide.”

Respimat® Soft Mist Inhaler (SMI) is a new generation inhaler that provides a unique, slow moving and long-lasting soft mist5,6 that is easy to inhale7 and produces superior lung deposition.8,9 Respimat® SMI is preferred by patients compared to other currently available inhalers.10,11,12

On the back of promising olodaterol data, Boehringer Ingelheim is currently studying the efficacy of a once-daily fixed-dose combination of tiotropium and olodaterol in the TOviTO Phase III trial program. The TOviTO program includes several trials that could provide important evidence to support the potential of tiotropium and olodaterol to improve patients’ lives beyond optimal bronchodilation.

About COPD
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death and disability throughout the world. COPD has a significant physical and emotional impact on those who suffer from the disease.13 As COPD progresses, the onset of shortness of breath results in the decline of lung function and becomes a major cause of disability and anxiety in patients.14 This can lead to people feeling afraid, frustrated, isolated and depressed.14,15 The latest World Health Organisation (WHO) figures estimate that more than 21 million people are currently living with COPD.16 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.17 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.18

About Olodaterol
Olodaterol is a true once-daily, long-acting ß2-agonist (LABA) that Boehringer Ingelheim has designed and developed as an ideal partner to tiotropium for patients with COPD. To date, olodaterol’s efficacy as a true once-daily bronchodilator could be shown in clinical studies, with an significant increase in lung function for at least 24 hours in patients with 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 program. The TOviTO program includes several trials that could provide important evidence to support olodaterol’s potential to improve patients’ lives beyond optimal bronchodilation.

About Tiotropium
Tiotropium (Spiriva®) is a long-acting inhaled anticholinergic medication and is the first inhaled maintenance treatment to provide significant and sustained improvements in lung function with once-daily dosing. Tiotropium positively impacts the clinical course of COPD, helping to change the way patients live with their disease,19,20 by opening narrowed airways and helping to keep them open for 24 hours. Tiotropium works through targeting a dominant reversible mechanism of COPD – cholinergic bronchoconstriction (closing of the airways) – and has demonstrated significant and sustained bronchodilation21 (opening of the airways) and reduction in hyperinflation22,23 (air trapping). Tiotropium 18 µg administered via HandiHaler® has been shown to be superior to salmeterol 50 µg via HFA (metered-dose inhaler/MDI), in reducing the risk of exacerbations in COPD24. Boehringer Ingelheim has marketed tiotropium as Spiriva® since 2002 (10 years).

About Respimat® Soft Mist™ Inhaler
Developed by Boehringer Ingelheim, Respimat® Soft Mist™ Inhaler (SMI) is a propellant-free, new generation inhaler with a unique delivery mechanism. It produces a long-lasting, slow moving Soft Mist™5,6 that is easy to inhale, easy to co-ordinate (forced inhalation is not required), reduces deposition in the mouth and throat and leads to superior lung deposition.7,8,9 Respimat® SMI is preferred by patients compared to other currently available inhalers.10,11,12

Olodaterol is an investigational compound. Its safety and efficacy have not yet been fully established

Boehringer Ingelheim: Leading respiratory forward
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 field. In addition to new novel treatments for COPD, Boehringer Ingelheim has also branched out into developing treatment options for other airway diseases, including asthma, lung cancer, idiopathic pulmonary fibrosis and other respiratory indications. Boehringer Ingelheim’s respiratory portfolio covers a wide range of treatment options and includes Spiriva® (tiotropium), Berodual® (fenoterol/ipratropium), Berotec® (fenoterol), Combivent® (ipratropium/salbutamol) and Atrovent® (ipratropium).

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 act 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 endeavors.

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

References

1 van Noord JA, et al., 24-hour Bronchodilation following a single dose of the novel b2-agonist olodaterol in COPD, Pulmonary Pharmacology & Therapeutics 2011, 24 (6) 666-672
2 van Noord JA, Korducki L, Hamilton AL and Koker P. ATS Poster 2009: Four Weeks Once Daily Treatment with BI 1744, a Novel Long-Acting ß2-Agonist, is Effective in COPD Patients
3 Joos G, Aumann JL, Coeck C, et al. ATS 2012 Abstract: Comparison of 24-Hour FEV1 Profile for Once-Daily versus Twice-Daily Treatment with Olodaterol, A Novel Long-Acting ß2-Agonist, in Patients with COPD. 
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15Maurer J , Rebbapragada B, Borsen S. et al. Anxiety and depression in COPD. Chest 2008;134;43S-56S.
16World Health Organization. Global Alliance Against Chronic Respiratory Diseases. 2008. [Online] Available at: http://www.who.int/gard/publications/Istanbul_report_final.pdf [Last accessed: February 2012].
17Yawn 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.
18Wilkinson 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.
19Casaburi R, Kukafka D, Cooper CB, et al. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest 2005; 127: 809-817
20Vincken W, van Noord JA, Greefhorst APM, et al. Improved health outcomes in patients with COPD during 1 year’s treatment with tiotropium. Eur Respir J 2002; 19: 209-216
21Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J 2002; 1: 217-224
22Celli B, ZuWallack R, Wang S, et al. Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes. Chest 2003; 124: 1743-1748
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24Vogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011;364(12)
25SCARSIN 2011

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