Phase III Results: Once-daily Tiotropium* Effective in Symptomatic Asthma Patients Irrespective of Their Age, Allergic Status, Smoking Status and Bronchodilator Response

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21 May, 2013, 13:07 GMT

BRACKNELL, England, May 21, 2013 /PRNewswire/ --

For UK medical, health correspondents and business media

Tiotropium delivered by the Respimat® Soft Mist™ Inhaler (SMI) increases time to first severe exacerbation and first episode of asthma worsening across a broad spectrum of patients who remain symptomatic despite at least inhaled corticosteroids (ICS) / long-acting β₂-agonists (LABA) therapy ¹
The results are from pre-planned subgroup analyses of data from the PrimoTinA-asthma™ Phase III studies being presented for the first time today at the 2013 American Thoracic Society (ATS) congress in Philadelphia, Pennsylvania ^1;2

* Please note: tiotropium delivered by Respimat is not licensed for the treatment of asthma.

Tiotropium delivered by the Respimat Soft Mist Inhaler increases time to first severe exacerbation (p=0.03) and first episode of asthma worsening (p<0.001) compared with placebo in symptomatic asthma patients receiving standard care treatments (ICS/LABA). These improvements were independent of age, allergic status, smoking status and bronchodilator response.¹

Commenting on the PrimoTinA-asthma subgroup analyses, Dr Richard Russell, Consultant Chest Physician, Wexham Park Hospital (and one of the UK study investigators) said, "These results are extremely encouraging as we continue to investigate tiotropium as a potential treatment for asthma. There remains a significant number of asthma patients who continue to be symptomatic despite available therapeutic options. The results suggest tiotropium may be an efficacious treatment option for patients."

Given the known effectiveness of tiotropium in COPD and the significant benefit observed in COPD patients with concomitant features of asthma, it was important to investigate whether it could be confirmed that the patients included in the PrimoTinA-asthma Phase III studies had asthma alone.

Presenting the analysis of the baseline characteristics of the PrimoTinA-asthmapatient population, Professor David Halpin, Consultant in Respiratory Medicine, Royal Devon and Exeter Hospital, UK, showed that the age of onset, duration of symptoms, smoking status, allergic status and bronchodilator response in the PrimoTinA-asthma patient population provide reasonable certainty that the patients enrolled in these Phase III studies had asthma and not COPD.²

Professor Halpin 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 thePrimoTinA-asthma studies therefore represents improvement of the patients' asthma."

Despite standard treatment options, an estimated 55% of patients with asthma remain symptomatic and may experience life-threatening asthma exacerbations.³ All patients in the PrimoTinA-asthma studies were symptomatic despite receiving standard care asthma treatments (ICS/LABA).^1;2

The PrimoTinA-asthma studies 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 (less than 10 pack-years 1 pack of cigarettes daily for 10 years**) who quit smoking one or more years before study enrolment.^1;2

A total of 912 patients were randomised to additional tiotropium Respimat 5 mcg (n=456) or placebo (n=456) for 48 weeks. In addition to ICS/LABA, patients in the PrimoTinA-asthma studies were permitted to receive additional background therapy, including theophylline, anti-allergic agents, stable systemic steroids and omalizumab.⁴

Asthma diagnosis in the PrimoTinA-asthma 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

Severe exacerbations were defined as asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids.¹

"Boehringer Ingelheim has a long-established commitment and heritage in respiratory disease. These results are extremely promising as they further demonstrate the potential that once-daily tiotropium Respimat could have across a broad range of patients. Tiotropium has the potential to provide healthcare professionals with an add-on treatment for symptomatic asthmatic patients," said Dr Brian Wong, Head of UK Medical and Scientific Affairs, Boehringer Ingelheim.

** 1 pack of cigarettes daily for 10 years

Notes to Editors

UniTinA-asthma Phase III trial programme ongoing

The PrimoTinA-asthma studies are part of Boehringer Ingelheim's comprehensive ongoing Phase III trial programme named UniTinA-asthma, which was designed to establish the efficacy and safety of tiotropium, delivered by the Respimat Soft Mist Inhaler (SMI) in patients with asthma. UniTinA-asthma includes trials in adults, adolescents and children and involves over 4,000 patients in more than 150 sites globally. Included in the UniTinA-asthma umbrella programme are the following studies:

PrimoTinA-asthma Adult study - 205.416/.417 ^5;6
MezzoTinA-asthma Adult study - 205.418/.419 ^7;8
GraziaTinA-asthma Adult study - 205.442 ⁹
VivaTinA-asthma Paediatric study - 205.445/.446 ^10;11
RubaTinA-asthma Adolescent study - 205.444 ¹²
PensieTinA-asthma Adolescent study - 205.456 ¹³

About Asthma

Asthma is a chronic disorder of the airways, caused primarily by inflammatory processes and constriction of the smooth muscle in airway walls (bronchoconstriction). It is characterised by airflow obstruction and increased responsiveness of the airways to various stimuli (known as triggers). Symptoms include recurring episodes of wheezing, breathlessness, chest tightness and coughing. Typical asthma symptoms tend to be variable, intermittent and worse at night. Asthma is commonly triggered by viral respiratory infections, exercise, smoke, cold and allergens such as pollen, mould, animal fur and the house dust mite.¹⁴

The prevalence of asthma in England is among the highest in the world, with approximately 5.9% of the English population having asthma.¹⁵

Asthma is responsible for large numbers of unscheduled emergency admissions. 70% of unscheduled emergency admissions may have been preventable with appropriate early interventions.¹⁵

Epidemiological data have shown that many adults with asthma remain symptomatic despite current treatment options and have asthma exacerbations (attacks)¹⁶ and might even require emergency care.¹⁴

There is no cure for asthma, although people may experience long periods of remission. Poorly controlled asthma can have a significant impact on the quality of life of the affected person and their family. Clinical measures such as lung function may not correlate with an individual's quality of life scores, but if asthma is well controlled, near maximal scores on quality of life instruments can be achieved.¹⁴

About Tiotropium

Tiotropium (Spiriva®) is a long-acting muscarinic antagonist (LAMA) with a mode of action that works by opening narrowed airways by targeting a dominant reversible mechanism - cholinergic bronchoconstriction and helping to keep them open for 24 hours with once-daily dosing.^17;18

Tiotropium is licensed for the treatment of chronic obstructive pulmonary disease (COPD) symptoms and has comprehensive clinical trial data, demonstrating extensive experience since its introduction almost 11 years ago and over 25 million patient years of real life experience to support the efficacy and safety profile.¹⁹

About Respimat SMI

Respimat SMI is an innovative delivery device, which uses mechanical energy (a spring) to generate a long-lasting, slow-moving mist for inhalation.^18;20

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 novel treatments for asthma, Boehringer Ingelheim has also branched out into developing treatment options for other airway diseases, including COPD, lung cancer, idiopathic pulmonary fibrosis and other respiratory indications.

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 endeavors.

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

References

(1) Kerstjens H.A.M, Tashkin D.P, Engel M. Tiotropium decreases the risk of exacerbations in patients with symptomatic asthma regardless of baseline characteristics. American Thoracic Society (ATS) congress. Philadelphia, Pennsylvania. A0846. 2013.

(2) Halpin D.M, Bateman E.D, Moroni-Sentgraf P. Tiotropium is effective in patients with severe asthma without evidence of chronic obstructive pulmonary disease. American Thoracic Society (ATS) congress. Philadelphia, Pennsylvania. A40590. 2013.

(3) Peters S.P, et al. Real-world Evaluation of Asthma Control and Treatment (REACT): Findings from a national Web-based survey. 2007: 1454-1461.

(4) Kerstjens H.A.M, Engel M, Dahl R et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012; 367(13):1198-1207.

(5) ClinicalTrials.gov. Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I). Available at http://clinicaltrials.gov/ct2/show/NCT00772538. Accessed May 2013.

(6) ClinicalTrials.gov. Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study II). Available at http://clinicaltrials.gov/ct2/show/NCT00776984. Accessed May 2013.

(7) ClinicalTrials.gov. Evaluation of Tiotropium 2.5 and 5 Mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and SalmeterolHydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 Mcg Twice Daily) in Patient With Moderate Persistent Asthma I. Available athttp://clinicaltrials.gov/ct2/show/NCT01172808. Accessed May 2013.

(8) ClinicalTrials.gov. Evaluation of Tiotropium 2.5 and 5 Mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and SalmeterolHydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 Mcg Twice Daily) in Patient With Moderate Persistent Asthma II. Available athttp://clinicaltrials.gov/ct2/show/NCT01172821. Accessed May 2013.

(9) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma. Available athttp://clinicaltrials.gov/ct2/show/NCT01316380. Accessed May 2013.

(10) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Moderate Persistent Asthma.Available at http://clinicaltrials.gov/ct2/show/NCT01634139. Accessed May 2013.

(11) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma.Available at http://clinicaltrials.gov/ct2/show/NCT01634152. Accessed May 2013.

(12) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01257230. Accessed May 2013.

(13) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma.Available at http://clinicaltrials.gov/ct2/show/NCT01277523. Accessed May 2013.

(14) National Institute for Health and Clinical Excellence (NICE). Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. 2008.

(15) Department of Health. An Outcomes Strategy for Chronic Obstructive Pulmonary Disease (COPD) and Asthma in England. 2011.

(16) Rabe K.F, Adachi M, Lai C.K 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):40-47.

(17) Boehringer Ingelheim. Spiriva 18 microgram inhalation powder, hard capsule. Summary of Product Characteristics. (The Electronic Medicines Compendium) www.medicines.org.uk. Accessed May 2013.

(18) Boehringer Ingelheim. Spiriva Respimat 2.5 micrograms solution for inhalation. Summary of Product Characteristics. (The Electronic Medicines Compendium) www.medicines.org.uk. Accessed May 2013.

(19) Boehringer Ingelheim. Data on File: SPI11-03. 2011.

(20) Hochrainer D, Hölz H, Kreher C et al. Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers. J Aerosol Med 2005; 18(3):273-282.

For further information, please contact: Nick Johnson, Communications Manager, Boehringer Ingelheim Limited, Tel: +44-(0)1344-746792,nick.johnson@boehringer-ingelheim.com