Value through Innovation28 August 2014
23 February 2013

Phase III results: tiotropium* Respimat® is effective in symptomatic asthma patients irrespective of their allergic status

New Phase III data presented for the first time at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting

San Antonio, Texas, 23rd February, 2013 – Tiotropium delivered once daily via Respimat™ significantly improved lung function and reduced asthma exacerbations in patients who remain symptomatic despite treatment with at least ICS/LABA, irrespective of their allergic status.1

These were the main findings from a new subset of data1 from the Phase III UniTinA-asthma® programme presented for the first time today at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in San Antonio, Texas.

"Patients with asthma may respond differently to treatment based on their allergic status, therefore it is important to investigate new therapies in both allergic and non-allergic patients," said Dr. Mark Vandewalker, MD, director, Clinical Research of the Ozarks, Columbia, Missouri. "The results of these trials show that tiotropium provides additional bronchodilation and reduces exacerbation rates in asthmatics who are symptomatic on current therapy with at least ICS/LABA regardless of their allergic status, demonstrating its potential benefit for patients who need additional asthma control."

The PrimoTinA-asthmaTM studies (1 and 2) were two replicate double-blind parallel-group trials including asthma patients with post-bronchodilator FEV1§<80% predicted and Asthma Control Questionnaire score ≥1.5 while on at least ICS/LABA. A total of 912 patients were randomised to additional tiotropium Respimat® 5 µg (n=256) or placebo (n=256) for 48 weeks.

In addition to ICS/LABA, patients in the trials were permitted to receive additional background therapy, including antihistamines, anti-allergic agents, nasal steroids and omalizumab.

To investigate the relationship between response and the patients' allergic status, a pre-planned sub-group analysis of the data from both PrimoTinA-asthmaTM studies (1 and 2) was carried out.

The subgroup of patients with potentially allergic asthma was identified using three criteria: total serum immunoglobulin E (IgE), blood eosinophils, or clinician judgment. Allergic status was positive if serum IgE was greater than 430 μg/L, blood eosinophilia was greater than 0.6 × 109/L, or clinician judgement was "yes."

In the overall study population, adding tiotropium Respimat® provided significant lung function improvements at 24 weeks, which were sustained over 48 weeks.1 Also, patients who received tiotropium Respimat® had a 21% risk reduction (HR 0.79, P=0.03) in time to first severe exacerbation. Severe exacerbations were defined as requiring systemic corticosteroids for at least 3 days.1

Furthermore, the addition of tiotropium Respimat® reduced the risk of any asthma exacerbation, defined by a significant increase in symptoms or peak expiratory flow (PEF) drop >30% over >2 days, by 31% (P<0.0001).1

These significant improvements in lung function and reduction in exacerbations were also seen regardless of allergic status in each of the two trials. The pre-planned subgroup analyses showed that peak FEV1 improved with tiotropium in PrimoTinA-asthmaTM 1 irrespective of allergic status for IgE (P=0.86) and eosinophilia (P=0.46), and in PrimoTinA-asthmaTM 2 for IgE (P=0.98) and eosinophilia (P=0.18). There was also an improvement in clinician judgment in PrimoTinA-asthmaTM 2 (P=0.29).

Pre-dose (trough) FEV1 also improved with tiotropium compared with placebo, irrespective of allergic status, across all criteria in Trial 1 (IgE, P=0.85; eosinophilia, P=0.83; clinician judgment, P=0.15) and Trial 2 (IgE, P=0.58; eosinophilia, P=0.38; clinician judgment, P=0.85).

Pooled pre-specified data analyses from the two trials revealed that time to first severe asthma exacerbation and time to first asthma worsening were both increased with tiotropium compared with placebo not just in the overall analysis of the data, but also regardless of the patients’ allergic status, based on the three criteria.

Adverse events (AEs) were balanced between the allergic and non-allergic sub groups. The most frequently reported treatment-emergent AEs in both Phase III studies included asthma, peak expiratory flow (PEF) rate decreased and nasopharyngitis.

Prof. Dr. Klaus Dugi

Prof. Dr. Klaus Dugi

"The UniTinA-asthmaTM 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 the available therapeutic options. This programme demonstrates our commitment to develop tiotropium Respimat® for a wide range of asthma patients," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "We are encouraged by these findings, as they provide us with more information on the potential of tiotropium Respimat® across new subsets of asthma patients," Professor Dugi concluded.

Notes to editors
About UniTinA-AsthmaTM
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 MistTM Inhaler (SMI) in patients with asthma.

UniTinA-asthmaTM includes a number of clinical studies investigating tiotropium Respimat® added to usual care in adults, adolescents and 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. 2, 3 Despite all current treatment options, a significant number of patients with asthma remain symptomatic and may experience frightening and life-threatening asthma exacerbations (attacks).4,5

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.6 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.6 People suffering from asthma experience recurrent episodes of wheezing, breathlessness, chest tightness and coughing.6

Estimates of the numbers of people affected by asthma worldwide vary from 235 to 300 million.7,8 Worldwide, approximately 180,000 deaths are attributable to asthma each year,8 although there is considerable regional variation in mortality rates.9

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, a significant number of patients suffer from uncontrolled asthma despite the available treatment options.4,5 They can continue to have symptoms and lifestyle restrictions and might even require emergency care.

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.

About Respimat® Soft MistTM Inhaler
Developed by Boehringer Ingelheim, Respimat® Soft MistTM Inhaler (SMI) is a new generation inhaler delivering a unique Soft MistTM10,11 that is easy to inhale,12 and is preferred by patients compared to other currently available inhalers.13-16

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 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 act in a socially responsible manner. 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.

   
Pfizer Inc: Working together for a healthier worldTM
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global healthcare portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world’s best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world’s leading biopharmaceutical company, we also collaborate with healthcare providers, governments and local communities to support and expand access to reliable, affordable healthcare around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

To learn more about our commitments, please www.pfizer.com

References
1. Vandewalker, M., et al. Efficacy of tiotropium in patients with asthma in relation to allergic status. PrimoTinA-asthma AAAAI 2013 Abstract
2. 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
3. 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
4. Rabe, KF, Vermeire, PA, Soriano, JB, et al Clinical management of asthma in 1999: the Asthma Insights in Europe (AIRE) study. Eur Respir J 2000; 16, 802-807
5. Rabe KF, Adachi M, Lai CK et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol. 2004; 114(1): 40-7.
6. Global Initiative for Asthma (GINA). http://www.ginasthma.org/Questions-and-answers/q-a-general-information-about-asthma.html [Last Accessed 11/02/13]
7. World Health Organization. WHO factsheet 307: bronchial asthma. Available at: http://www.who.int/mediacentre/factsheets/fs307/en/index.html [Last Accessed 11/02/13]
8. Braman SS. The global burden of asthma. Chest. 2006 Jul;130(1 Suppl):4S-12S.
9. http://www.ginasthma.org/pdf/GINABurdenReport.pdf published in 2003 [Last Accessed 11/02/13]
10. Dhand R. Aerosol Plumes: Slow and Steady Wins The Race. J Aerosol Med 2005; 18(3): 261-63
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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.

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* Tiotropium delivered by Respimat® is not licensed for the treatment of asthma and is not approved in the US

Inhaled corticosteroids

Long-acting beta2-agonists

§ FEV1 Forced Expiratory Volume in one second

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