BOEHRINGER-INGELHEIM

• Tiotropium delivered by the Respimat ^® SoftMist ^TM Inhaler increases time to first severe exacerbation and first episode of asthma worsening across a broad spectrum of patients who remain symptomatic despite at least ICS/LABA therapy
• The improvements in lung function with tiotropium were specific to asthma patients; as a co-morbid condition, chronic obstructive pulmonary disease (COPD) was excluded in this trial

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In patients with symptomatic asthma despite at least ICS/LABA therapy, tiotropium delivered by the Respimat® SoftMist^TM Inhaler increases time to first severe exacerbation and first episode of asthma worsening. This improvement is independent of age, allergic status, smoking status and bronchodilator response.¹

This was the main finding from pre-planned subgroup analyses of data from the PrimoTinA- asthma^TM Phase III studies being presented for the first time at the 2013 American Thoracic Society (ATS) congress in Philadelphia, Pennsylvania.¹

In addition, the results of a detailed analysis of the baseline characteristics of the PrimoTinA-asthma^TM patient population² were reported at the meeting. This analysis showed that the age of onset, duration of symptoms, lack of smoking, allergic status and bronchodilator response in the PrimoTinA asthma^TM patient population provide reasonable certainty that the patients enrolled in these Phase III studies had asthma and not COPD.²

Reporting on the PrimoTinA-asthma^TM subgroup analyses, Professor Huib A M Kerstjens of the University Medical Centre, Groningen, The Netherlands said, "These results indicate that tiotropium is effective across a broad spectrum of patients who remain uncontrolled and experience asthma exacerbations despite standard combination use of moderate-to high-dose inhaled corticosteroids (ICS) plus long-acting beta-agonists (LABA). Furthermore, the increase in time to first severe exacerbation and first episode of asthma worsening found with the addition of tiotropium was not limited to specific subgroups of patients.

“The improvements were, for example, similar between older and younger patients, between allergic and nonallergic patients, between highly reversible^§ and less reversible patients, and between ex-smokers and patients who had never smoked,” Professor Kerstjens explained.

Given the known effectiveness of tiotropium in COPD and the significant benefit observed in COPD patients with concomitant features of asthma,³ it was important to investigate whether patients included in the PrimoTinA-asthma^TM Phase III studies could be confidently considered to have asthma alone.

Presenting the detailed analysis of the baseline characteristics of the PrimoTinA-asthma^TM patient population, Professor David Halpin, Consultant in Respiratory Medicine, Royal Devon and Exeter Hospital, UK said, “These results provide us with evidence that the patients in these studies, which showed the efficacy of tiotropium, had clinical features typical of asthma, rather than COPD; any similarities to COPD were due to the longstanding nature of their asthma. The efficacy demonstrated in the PrimoTinA-asthma^TM studies therefore represents improvement of the patients’ asthma," Professor Halpin concluded.

Despite current treatment options, at least 40% of patients with asthma remain symptomatic and may experience frightening and life-threatening asthma exacerbations (attacks).⁴ All patients in the PrimoTinA-asthma^TM studies were symptomatic despite at least ICS/LABA therapy.

The PrimoTinA-asthma^TM studies (1 and 2) were two replicate double-blind parallel-group trials including asthma patients aged 18-75 years, with a ≥5-year history of asthma, diagnosed before the age of 40 years; and life-long non-smokers, or ex-smokers who smoked less than 10 pack-years^** and who quit smoking 1 or more years before study enrolment.¹

A total of 912 patients were randomised to additional tiotropium Respimat® 5 μg (n=456) or placebo (n=456) for 48 weeks. In addition to ICS/LABA, patients in the PrimoTinA-asthma^TM studies were permitted to receive additional background therapy, including antihistamines, anti-allergic agents, nasal steroids and omalizumab.^1,2

Asthma diagnosis in the PrimoTinA-asthma^TM patient population was confirmed using criteria in line with current Global Initiative for Asthma guidelines.² Patients with a diagnosis of COPD or other lung disease were excluded from the studies.²

In the overall study population, the time to first severe exacerbation was prolonged by the addition of tiotropium Respimat® (risk reduction 21%; hazard ratio 0.79; p=0.03). The time to first episode of asthma worsening was increased in the tiotropium group compared with placebo (risk reduction 31%; hazard ratio 0.69; p<0.001).¹ Severe exacerbations were defined in the PrimoTinA-asthma^TM studies as asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids.¹

Subgroup analyses showed that neither the improvement in time to first severe exacerbation nor the time to first episode of asthma worsening found with the addition of tiotropium Respimat® was dependent on baseline characteristics, and was not limited to specific subgroups of patients.

The PrimoTinA-asthma^TM studies are part of a large international Phase III clinical programme involving more than 4,000 patients, named UniTinA-asthma®.

“The UniTinA-asthma® trial programme is exploring whether tiotropium can address the clear unmet medical need seen in the significant number of asthma patients who remain symptomatic despite using the available therapeutic options. This programme demonstrates our commitment to profile tiotropium Respimat® for the full range of asthma patients from mild to very severe across all age groups,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim.

Notes to editors

About UniTinA-Asthma®

The PrimoTinA-asthma™ studies are a part of Boehringer Ingelheim’s large international phase III clinical programme named UniTinA-asthma®, which was designed to establish the efficacy and safety of tiotropium, delivered by the Respimat® Soft Mist^TM Inhaler (SMI) in patients with asthma.

UniTinA-asthma® includes a number of clinical studies investigating tiotropium Respimat^® added to usual care in adults, adolescents and children (age 1+) with persistent asthma across the spectrum of asthma severity.

The current phase III programme consists of 11 studies and involves more than 4,000 patients in over 150 sites globally. Data from two of these Phase III clinical trials were presented for the first time at the ERS 2012 congress. ^5,6

The UniTinA-asthma® Phase III clinical trial programme is addressing the unmet need of patients who remain symptomatic despite today’s therapies.

About Asthma

Asthma is a chronic disease characterised by airway inflammation and bronchoconstriction, leading to limited airflow into and out of the lungs and an increased production of mucus.⁷

When a person with asthma comes into contact with an asthma trigger (e.g. infections, pollen, smoke), their airways can become more inflamed, swollen and constricted and excess mucus is produced. These reactions cause the airways to become narrower and irritated, making it difficult to breathe.⁷

People suffering from asthma experience recurrent episodes of wheezing, breathlessness, chest tightness and coughing.⁷

Estimates of the numbers of people affected by asthma worldwide vary from 100 to 300 million, with these numbers predicted to grow to as many as 400-450 million people worldwide by 2025.^8,9 The prevalence of asthma is highest in industrialised countries. Worldwide, approximately 180,000 deaths are attributable to asthma each year,⁹ although there is considerable regional variation in mortality rates.¹⁰

The economic costs associated with asthma are estimated to rank as one of the highest among chronic diseases. Globally, the economic costs associated with asthma exceed those of tuberculosis and HIV/AIDS combined.¹⁰

By avoiding asthma triggers, one can help to reduce the severity of asthma. Although asthma cannot be cured, appropriate management can control the disease and enable people to enjoy a good quality of life. However, epidemiological data have shown that, despite treatment, at least 40% of adults with asthma remain symptomatic, which could result in lifestyle restrictions, and might even require emergency care.⁴ These patients could benefit from new treatment options.

About Tiotropium

Tiotropium is a long-acting inhaled anticholinergic bronchodilator and was the first inhaled maintenance treatment to provide significant and sustained improvements in lung function in COPD patients with once-daily dosing. Tiotropium works by opening narrowed airways and helping to keep them open for 24 hours.

The tiotropium in asthma clinical development programme is being jointly developed by Boehringer Ingelheim and Pfizer with Boehringer Ingelheim managing the operations for all clinical development activities. The existing alliance contract between Boehringer Ingelheim and Pfizer allows for commercialisation by both companies.

About Respimat® Soft Mist ^TM Inhaler

Developed by Boehringer Ingelheim, Respimat® Soft Mist^TM Inhaler (SMI) is a new generation inhaler delivering a unique Soft Mist^TM12,13 that is easy to inhale,¹⁴ and is preferred by patients compared to other currently available inhalers.^15-16

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 once-daily maintenance prescription medicine for COPD. Boehringer Ingelheim has also branched out into developing treatment options for other airway diseases, including lung cancer and idiopathic pulmonary fibrosis.

Our promising future in respiratory is driven by our leadership and passion for unraveling the complex science behind debilitating diseases that confront people living with lung conditions today and those that will surface tomorrow.

Boehringer Ingelheim

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 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 endeavours.

In 2012, Boehringer Ingelheim achieved net sales of about 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.boehringer-ingelheim.com

NewsHome: An innovative resource for journalists

The Boehringer Ingelheim respiratory www.NewsHome.com is available and is the one-stop-shop for clear, concise and easy to understand information about asthma and other respiratory illness for the media.

^* Please note: tiotropium delivered by Respimat® is not licensed for the treatment of asthma and is not yet approved.

^† Inhaled corticosteroids

^‡ Long-acting beta2-agonists

^§ increase in lung function in response to an inhaled bronchodilator

^** 1 pack of cigarettes daily for 10 years

References

1. Kerstjens HAM, Tashkin DP, Engel M et al. Tiotropium decreases the risk of exacerbations in patients with symptomatic asthma regardless of baseline characteristics. Am J Respir Crit Care Med 2013; 187: A4217

2. Halpin DM, Bateman ED, Moroni-Zentgraf P, et al. Tiotropium is effective in patients with severe asthma without evidence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 187: A2731

3. Magnussen H , Bugnas B , van Noord J , et al. Improvements with tiotropium in COPD patients with concomitant asthma. Respir Med . 2008; 102(1): 50-6

4. Bateman ED , Boushey HA , Bousquet J , et al; GOAL Investigators Group . Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med. 2004;170 (8): 836-44

5. Kerstjens HAM, Dahl R, Beck E, et al. Tiotropium reduces asthma exacerbations in asthmatic patients with persistent airflow obstruction uncontrolled despite treatment in accordance with guidelines. Eur Respir J 2012; 40: Suppl. 56, 313S abstract P1796

6. Kerstjens HAM, Paggiaro PL, Vandewalker et al. Tiotropium provides sustained bronchodilation in asthmatics with persistent airflow obstruction uncontrolled despite treatment in accordance with guidelines. Eur Respir J 2012; 40: Suppl. 56, 391S abstract P2187

7. Global Initiative for Asthma. Pocket guide for asthma management and prevention. Available at: http://www.ginasthma.org/local/uploads/files/GINA_Pocket_Guide_2012_wms.pdf [Last Accessed 11/04/13]

8. World Health Organization. WHO factsheet 307: bronchial asthma. Available at: http://www.who.int/mediacentre/factsheets/fs307/en/index.html [Last Accessed 11/04/13]

9. Braman SS . The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S

10. Global Initiative for Asthma. http://www.ginasthma.org/pdf/GINABurdenReport.pdf published in 2003 [Last Accessed 11/04/13]

11. World Health Organization. WHO factsheet 206: bronchial asthma. Available at: http://www.who.int/mediacentre/factsheets/fs206/en/ [Last Accessed 11/04/13]

12. Dhand R. Aerosol Plumes: Slow and steady wins the race. J Aerosol Med 2005; 18(3): 261-63

13. Hochrainer D, Hölz H. Comparison of aerosol velocity and spray duration of Respimat® Soft Mist^TM Inhaler and pressurized Metered Dose Inhalers. J Aerosol Med 2005; 18(3): 273-282

14. Kardos P, Golisch W, Wolf K. New SoftMist^TM Inhaler is effective and easy to use in patients with asthma and COPD. Eur Respir J 2005; 26 (Suppl 49): 338s

15. Hodder R, Reese PR, Slaton T. Asthma patients prefer Respimat® Soft Mist^TM Inhaler to Turbohaler. Int J Chronic Obstruct Pulm Dis 2009; 4: 225-232

16. Schuermann W, Schmidtmann S, Moroni P, et al. Respimat® Soft Mist^TM Inhaler versus hydrofluroalkane metered dose inhaler: patient preference and satisfaction. Treatm Respir Med 2005;4 : 53-61

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