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

Burlington, Ontario, September 9, 2013 – 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^®.*

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