Landmark TIOSPIR(TM) trial reinforces value of SPIRIVA(R) in two formulations as one of the leading maintenance therapies for chronic obstructive pulmonary disease (COPD)

One of largest COPD trials ever conducted confirms comparable safety and efficacy profile of SPIRIVA^® Respimat^®* 2.5 µg (once a day, two puffs)^†† and SPIRIVA^® HandiHaler^® 18 µg

• Time to first COPD exacerbation was comparable for both SPIRIVA^® (tiotropium) formulations: Respimat^® 2.5 µg (once a day, two puffs) and HandiHaler^® 18 µg¹
• Building on the on-treatment mortality benefit of SPIRIVA^® 18 µg via HandiHaler^® vs. control in the milestone trial UPLIFT^‡2, the TIOSPIR™ trial showed a similar impact on survival between SPIRIVA^® Respimat^® and SPIRIVA^® HandiHaler^®1
• With broad inclusion criteria, the TIOSPIR™ trial population was representative of typical, real-world COPD patients, including patients with all COPD disease assessment categories (GOLD^§ groups A-D), comprehensive use of concomitant COPD medications, and patients with a history of cardiac disorders¹

BURLINGTON, ON, Sept. 9, 2013 /CNW/ - TIOSPIR™ (Tiotropium Safety and Performance in Respimat^®), with over 17,000 COPD patients included and one of the largest international COPD trials ever conducted, confirmed the comparable safety and efficacy profile of the two SPIRIVA^® formulations - SPIRIVA^® Respimat^® 2.5 μg (once a day, two puffs) and SPIRIVA^® HandiHaler® 18 μg.¹ The trial included two SPIRIVA^® delivery systems, the unique Respimat^® inhaler and the dry powder inhaler HandiHaler^®.¹

The highly-anticipated results from the three year trial were published in the New England Journal of Medicine (on September 8, 2013). TIOSPIR™ was designed to provide evidence of the relative safety and efficacy profile of the investigational SPIRIVA^® Respimat^®2.5 μg (once a day, two puffs), or Respimat^® 1.25 μg (once a day, two puffs)** compared with SPIRIVA^® HandiHaler^® 18 µg.^†† TIOSPIR™ was specifically designed to be of an adequate size and duration, to enable analysis of all-cause mortality and time to first COPD exacerbation in a large COPD patient population, with broad inclusion criteria, which closely reflects the real-world COPD patient population.¹

Commenting on the results, Dr. Andrew McIvor, Professor of Medicine, McMaster University, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, said, "TIOSPIR™ is a landmark clinical trial which included 50 sites in Canada, providing evidence of the safety and efficacy of tiotropium delivered either by HandiHaler^® or Respimat^® in a broad population of COPD patients, including those with a history of cardiovascular disease. Importantly, the TIOSPIR™ trial reinforces that physicians can be confident in continuing to prescribe SPIRIVA^® HandiHaler^® as a proven maintenance therapy across the spectrum of different severities of COPD patients."

Efficacy as measured by time to first COPD exacerbation
The TIOSPIR^TM trial demonstrated comparable results for time to first COPD exacerbation for both formulations of SPIRIVA^®. In particular, the median time to COPD exacerbation was approximately two years for both formulations. For SPIRIVA^® Respimat^® 2.5 µg (once a day, two puffs) this was 756 days compared to 719 days for SPIRIVA^® HandiHaler^® 18 µg.¹

COPD exacerbations have a significant impact on patients' lives^3,4,5,6 and reducing their frequency and severity are principal goals of COPD treatment.⁷ The TIOSPIR™ results demonstrate that Respimat^® and HandiHaler^® showed comparable results for time to first COPD exacerbation, exacerbation frequency as well as rate of COPD exacerbations associated with hospitalization.

TIOSPIR™ builds upon the established efficacy profile of SPIRIVA^® HandiHaler^® as demonstrated in several trials, including the four year UPLIFT^®‡‡2 trial as well as a large-scale trial, POET-COPD^®§, which was specifically powered to investigate COPD exacerbations.⁸

• In the UPLIFT^®‡‡ trial, SPIRIVA^® 18 µg via HandiHaler^® was associated with reduction in the risk of exacerbations, related hospitalizations and respiratory failure vs. control (placebo)^2,9
• SPIRIVA^® 18 µg via HandiHaler^® demonstrated a 28 per cent reduction in the risk of a COPD exacerbation leading to hospitalization vs. the active comparator, the long-acting beta₂ agonist salmeterol, as observed in the POET-COPD^®§§ trial⁸
• In a separate trial, SPIRIVA^® Respimat^® 2.5 µg (once a day, two puffs) had a significant reduction in the risk of COPD exacerbations vs. placebo
  (31 per cent decrease)***¹⁰

Safety as measured by survival rates
The three year TIOSPIR™ trial also showed an equal impact on survival - as measured by all-cause mortality for tiotropium (SPIRIVA^® Respimat^® 2.5 µg (once a day, two puffs) vs. HandiHaler^® 18 µg).¹ This adds to evidence from the UPLIFT^®‡‡ trial in which Spiriva^® HandiHaler^® (18 µg) reduced the risk of death compared to control by 16 per cent (placebo) (P=0.016) and suggests an equally beneficial effect of the two SPIRIVA® formulations on survival.¹¹

Importantly TIOSPIR™ also demonstrated that:

• The incidence of adverse events and major adverse cardiovascular events was similar between the treatment groups¹
• In patients with a history of cardiac arrhythmia, SPIRIVA^® Respimat^® 2.5 μg (once a day, 2 puffs) and SPIRIVA^® HandiHaler^® 18 µg showed similar impact on survival as measured by all-cause mortality¹

COPD in Canada
Currently, COPD is the fourth leading cause of death in Canada and is expected to be the third leading cause of death worldwide by the year 2020.^12,13 Furthermore, mortality rates from COPD have risen over the past 15 years, particularly in women.¹²

It is estimated that hospital admissions for COPD lung attacks average a 10-day stay with a cost associated at approximately $10,000, resulting in an estimated total cost of COPD hospitalizations at a cost of $1.5 billion annually.¹⁴ Furthermore, over the next 25 years, it has been suggested that COPD will be responsible for approximately $101.4 billion in societal costs. The best strategy to reduce this financial burden is by reducing the number of COPD exacerbations that individuals experience.¹⁵

About TIOSPIR™¹
TIOtropium Safety and Performance In Respimat^® (TIOSPIR™), a global landmark trial in more than 17,000 patients, was one of the largest chronic obstructive pulmonary disease (COPD) trials ever conducted. Participants were recruited between May 2010 and April 2011 and were randomized to treatment in more than 1,200 investigator sites in 50 countries. The trial compared the safety and efficacy of SPIRIVA^® Respimat^® inhaler 2.5 μg (once a day, two puffs),^††† or SPIRIVA^® Respimat^® 1.25 μg (once a day, two puffs)^‡‡‡ with SPIRIVA^® HandiHaler^® 18 µg. Over the three-year duration of the trial, TIOSPIR™ demonstrated that SPIRIVA^® Respimat^® 5 μg or 2.5 µg have similar exacerbation, safety and efficacy outcomes to the well-established profile of SPIRIVA^® HandiHaler^® 18 µg in COPD. In a spirometry substudy of TIOSPIR™, involving 1,370 participants, Respimat^® 5 μg was non-inferior to HandiHaler^® for FEV₁, but the Respimat^® 2.5 μg dose was not.

SPIRIVA^® is delivered via HandiHaler^®, a breath-actuated, single-dose dry powder inhaler, or by SPIRIVA^® Respimat^® Inhaler™ propellant-free, new generation inhaler that combines innovative technology with the proven efficacy of SPIRIVA^®.^*

About Boehringer Ingelheim (Canada) Ltd.

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.

Social responsibility is a central element of Boehringer Ingelheim's 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 its Prescription Medicines business corresponds to 22.5 per cent of its net sales.

The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs more than 550 people across Canada.

For more information please visit www.boehringer-ingelheim.ca.

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*Tiotropium delivered by the Respimat^® inhaler is currently not authorized for sale in Canada
^††This is the dose referred to in the NEJM TIOSPIR™ publication as tiotropium Respimat^® 5 µg
^‡In UPLIFT^®, a trial of nearly 6,000 patients, SPIRIVA^® 18 µg via HandiHaler^® showed a 16 per cent reduction in the risk of death compared to control. While SPIRIVA^® 18 µg via HandiHaler^® did not alter the rate of decline in lung function, a coprimary study endpoint in the UPLIFT^® study, it sustained greater improvements in lung function vs. control (placebo)
^§ The GOLD report (international guidelines developed by the Global Initiative for Obstructive Lung Disease) classifies COPD patients into groups A-D, based on a combination of spirometry results, severity of symptoms, and risk of exacerbations
**The investigational doses of SPIRIVA^® Respimat^®, 1.25 µg (once a day, two puffs) and 2.5 µg (once a day, two puffs) are referred to in the NEJM TIOSPIR™ publication as tiotropium Respimat^® 2.5 µg and 5 µg respectively
^‡‡While SPIRIVA^® 18 µg via HandiHaler^® did not alter the rate of decline in lung function, a coprimary study endpoint in the UPLIFT^® study, it sustained greater improvements in lung function vs. control (placebo)
^§§The POET-COPD^® trial was a one-year, randomised, double-blind, double-dummy, parallel-group trial with a primary endpoint of time to first exacerbation, comparing once-daily SPIRIVA^® 18 μg via HandiHaler® with twice-daily salmeterol 50 μg via HFA-pMDI
^†††This is the dose referred to in the NEJM TIOSPIR™ publication as tiotropium Respimat^® 5 µg
^‡‡‡The investigational doses of SPIRIVA® Respimat®, 1.25 µg (once a day, two puffs) and 2.5 µg (once a day, two puffs) are referred to in the NEJM TIOSPIR™ publication as tiotropium Respimat® 2.5 µg and 5 µg respectively

 References

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*Tiotropium delivered by the Respimat^® inhaler is currently not authorized for sale in Canada
^1	Wise RA, Anzueto A, Cotton D, et al. Tiotropium Respimat Inhaler and the Risk of Death in COPD: The TIOSPIR Trial. N Engl J Med 2013; 369(10) DOI: 10.1056/NEJMoa1303342. (Presented at European Respiratory Society Congress 2013, Barcelona, Spain. TIOSPIR^®: Large scale trial of tiotropium Respimat^® vs HandiHaler^® (HH) in patients (pts) with COPD. Abstract P752, Sunday 8 September 2013).
^2	Tashkin DP, Celli B, Senn S, et al, on behalf of the UPLIFT^® (Understanding Potential Long-term Impacts on Function with Tiotropium) study investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543-1554.
^3	Soler-Cataluña JJ, Martínez-García MÁ, Román Sánchez P, et al. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 2005;60:925-31.
^4	Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet 2007;370:786-96.
^5	Miravitlles M, Anzueto A, Legnani D, et al. Patient's perception of exacerbations of COPD - the PERCEIVE study. Respir Med 2007;101(3):453-60.
^6	Donaldson GC, Seemungal TAR, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002;57:847-52.
^7	GOLD. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. 2013. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. (Accessed: June 2013).
^8	Vogelmeier C, Hederer B, Glaab T, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011;364(12):1093-1103.
^9	Celli B, Decramer M, Kesten S, et al. Mortality in the 4-Year Trial of Tiotropium (UPLIFT) in Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2009;180:948-955.
^10	Bateman E, Tashkin D, Siafakas N, et al. The one-year trial of tiotropium Respimat plus usual therapy in COPD patients. Respir Med 2010; 104: 1460-1472.
^11	Boehringer Ingelheim Canada Limited. SPIRIVA Product Monograph - revised August 21,  2012. Accessed August 2013 at http://www.boehringer-ingelheim.ca/content/dam/internet/opu/ca_EN/documents/humanhealth/product_monograph/Spiriva-pm.pdf.
^12	O'Donnell DE. Hernandez P. Kaplan A. Aaron S. Bourbeau J. Marciniuk D. et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2008 update -highlights for primary care. Can Respir J. 2008. 15(Suppl A):1A-8A.
^13	Camp PG. Levy RD. A snapshot of chronic obstructive pulmonary disease in British Columbia and Canada. BCMJ. 2008. 50(2): 80.
^14	Canadian Thoracic Society/Canadian Lung Association: The Human and Economic Burden of COPD. 2010. Accessed February 2012 at http://www.lung.ca/cts-sct/pdf/COPDReport_E.pdf.
^15	Najafzadeh M. Marra CA. Lynd LD. Sadatsafavi M. FitzGerald JM. McManus B. et al. Future Impact of Various Interventions on the Burden of COPD in Canada: A Dynamic Population Model. PLOS ONE. 2012. 7(10): 1-12.

SOURCE: Boehringer Ingelheim (Canada) Ltd.

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