Boehringer Ingelheim: new data from two trials showing Spiolto® Respimat® provides significant quality of life improvements in patients with moderate to severe COPD

• OTEMTO® 1&2 post-hoc analysis reinforces quality of life benefits provided by Spiolto® Respimat® right from the initial stage when patients first need maintenance therapy^*
• Head-to-head ENERGITO® study shows superior lung function improvements with Spiolto® Respimat® versus LABA/ICS FDC

AMSTERDAM, 29-9-2015 — /EuropaWire/ — Boehringer Ingelheim today announced new data from two trials presented at the European Respiratory Society (ERS) International Congress 2015. A post-hoc analysis from OTEMTO® 1&2 indicates that Spiolto® Respimat® provides significant quality of life improvements over Spiriva® Respimat® (tiotropium) or placebo, right from the initial stage when patients first need maintenance therapy.¹ These data support the role of Spiolto® Respimat® as a new 1^st line maintenance therapy for COPD^†. In addition the ENERGITO® study shows that the lung function improvement^§ with Spiolto® Respimat® (tiotropium/olodaterol) is superior to a steroid-containing therapy (LABA/ICS FDC^‡) in patients with moderate to severe COPD.²

From early in the course of COPD, decreasing lung function makes it more and more difficult for people to breathe. To cope with feeling breathless, patients reduce their activity and change their lifestyles which can lead to a ‘downward spiral’ of their condition.³ This in turn results in a large physical and emotional impact on people living with the disease.⁴ Providing optimal treatment right from the start of maintenance therapy can give patients the best chance of managing their symptoms, keeping active and maintaining their quality of life.

“These two trials further characterise the relevant benefits Spiolto® Respimat® provides compared to two commonly prescribed maintenance treatments: Spiriva® Respimat® and a LABA/ICS FDC,” said Dr William Mezzanotte, Vice President and Head of Respiratory Medicine at Boehringer Ingelheim. “The lung function and quality of life improvements shown in these trials add to the growing body of evidence supporting the benefit of using Spiolto® Respimat® at the initiation of maintenance therapy for COPD.”

OTEMTO® 1&2 – data reinforce Spiolto® Respimat® benefits as 1^st line maintenance therapy
A post-hoc analysis of the OTEMTO® 1&2 trials^* (NCT01964352/ NCT02006732), presented at ERS for the first time, shows that Spiolto® Respimat® provides a clinically meaningful 4 point improvement in quality of life^§§ compared to placebo in COPD patients with GOLD 2 disease.¹ In the same patient group, 13% more patients achieved a clinically meaningful improvement in quality of life with Spiolto® Respimat® compared to Spiriva® Respimat® (52.8% compared to 39.2%).⁵

“With no cure for COPD, improving quality of life is one of the major goals of treatment,” said Dave Singh, Professor of clinical pharmacology and respiratory medicine, University of Manchester. “When many patients are first diagnosed their condition is already declining rapidly. Doing as much as possible, early on, can give patients the best opportunity to maintain a good quality of life for longer. This sub-analysis shows that Spiolto® Respimat® could give patients this opportunity.”

These latest results add to the recently published OTEMTO® 1&2 data in Respiratory Medicine,⁶ which show Spiolto® Respimat® provides consistent improvements in lung function, breathlessness and quality of life over Spiriva® Respimat® (tiotropium) or placebo. The data also shows that Spiolto® Respimat® provides a safety profile similar to Spiriva® Respimat® or placebo. Incidence of adverse events (AEs) was broadly similar across treatment groups, with a higher incidence of AEs leading to discontinuation in the placebo groups compared to the treatment groups.⁶

ENERGITO® – superior lung function improvements over LABA/ICS FDC
Also presented for the first time, data from ENERGITO® (NCT01969721) show that Spiolto® Respimat® met all lung function endpoints , which included a 42% improvement in trough FEV₁, compared to the twice daily LABA/ICS salmeterol/fluticasone propionate in patients with moderate to severe COPD.²

ICS, or steroid-containing therapies, can be associated with potential serious side-effects and guidelines only recommend the use of these treatments in patients with severe COPD and frequent exacerbations (more than 2 per year).⁷ Despite this, in clinical practice ICS-based therapies are widely used across all COPD stages even for patients with low exacerbation risk who have less severe COPD. In this respect, the results from ENERGITO® add to data from the large-scale WISDOM study,⁸ raising questions about whether the benefits of ICS outweigh the potential side-effects associated with this class of treatment.

“ICS-containing therapies certainly have a role in the management of COPD but questions remain regarding when to use these treatments,” said Professor Kai-Michael Beeh, Insaf GmbH Institut für Atemwegs-forschung, Wiesbaden, Germany. “The ENERGITO® results further support the potential benefit of Spiolto® Respimat® as a COPD maintenance therapy and the notion that steroid-containing therapies may only be required in a population of patients with more severe stages of the disease and frequent exacerbations.”

The OTEMTO® 1&2 and ENERGITO® trials are part of the >15,000 patient TOviTO® Phase III clinical trial programme investigating the efficacy and safety of Spiolto® Respimat® in COPD. The results build on the pivotal phase III TONADO® trials that demonstrated Spiolto® Respimat® provides significant improvements in lung function, breathlessness, quality of life and reduction in rescue medication use over Spiriva® Respimat® right from the initial disease stages when patients first need maintenance therapy.^9,10 Data also showed that Spiolto® Respimat® was well tolerated with a favourable safety profile that was similar to tiotropium or olodaterol alone.⁹

About Spiolto® Respimat®
To date, Spiolto® Respimat® has been approved in more than 20 EU/EEA countries, the US, Canada and Australia for use in the treatment of patients with COPD.

Spiolto® Respimat® is built on tiotropium, the active ingredient in Spiriva® – the world’s most prescribed COPD maintenance treatment with over 40 million patient years of real life experience across all COPD severities.¹¹ It is enhanced by olodaterol^††, a unique and effective long-acting beta2-agonist with a fast onset of action,¹²specifically designed to complement the efficacy of Spiriva®. Spiolto® is delivered by Respimat®, which actively^‡‡ delivers a unique mist, meaning the patient just needs to take a slow deep breath.^13-19

For further information visit: http://newscentre.boehringer-ingelheim.com/education_hub1/respiratory.html

About COPD
COPD is a chronic, progressive, treatable but incurable lung disease that affects 210 million people worldwide.²⁰ It is a growing world health priority and is predicted to become the 3^rd leading cause of death by 2030.²¹

For people with COPD, decreasing lung function causes breathlessness and stops them from being active. This can lead to a downward spiral of worsening symptoms and even further inactivity,³contributing to an increased risk of disability and death.²²

Intended audiences
This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 146 affiliates and a total of more than 47,700 employees. The focus of the family-owned company, founded in 1885, is researching, developing, manufacturing and marketing new medications of high therapeutic value for human and veterinary medicine.

Social responsibility is an important element of the corporate culture at Boehringer Ingelheim. This includes worldwide involvement in social projects, such as the initiative “Making more Health” and caring for the employees. Respect, equal opportunities and reconciling career and family form the foundation of the mutual cooperation. In everything it does, the company focuses on environmental protection and sustainability.

In 2014, Boehringer Ingelheim achieved net sales of about 13.3 billion euros. R&D expenditure corresponds to 19.9 per cent of its net sales.

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

_________________________
^*  Results are derived from a post-hoc subgroup analysis of patients with moderate COPD (GOLD stage 2). The primary endpoints of the OTEMTO® studies were: FEV1 AUC_0-3, trough FEV₁, SGRQ total score in patients with moderate to severe COPD (GOLD stage 2–3).
^†  Chronic obstructive pulmonary disease
^§  FEV₁ AUC_0-12 response (primary endpoint), FEV₁ AUC_0-24, FEV₁ AUC_12-24 and trough FEV₁(secondary endpoint), all measured at 6 weeks
^‡  long acting beta2 agonist/inhaled corticosteroid fixed dose combination (FDC)
^§§  As measured by the St George’s Respiratory Questionnaire (SGRQ)
^**  FEV₁ AUC_0-12 response (primary endpoint), FEV₁ AUC_0-24, FEV₁ AUC_12-24 and trough FEV₁(secondary endpoint), all measured at 6 weeks
^††  Marketed as Striverdi® Respimat®
^‡‡  Respimat® delivers a metered dose of medication in a mist at the push of a button requiring just a slow deep breath from a patient

References

¹ Singh D, Ferguson GT, Bolitschek J, et al. Tiotropium + olodaterol fixed-dose combination shows clinically meaningful improvements in quality of life versus placebo. Poster PA2958 presented at the European Respiratory Society International Congress, Amsterdam, the Netherlands, 26-30 September 2015.
² Beeh KM, Derom E, Echave-Sustaeta J, et al. ENERGITO: efficacy and safety of once-daily combined tiotropium + olodaterol versus twice-daily combined fluticasone propionate + salmeterol. Poster PA4366 ERS 2015 abstract number: 750338
³ Reardon JZ, Lareau SC, ZuWallack R. Functional status and quality of life in chronic obstructive pulmonary disease. Am J Med 2006; 119(10 Suppl 1):32-7.
⁴ Confronting COPD in America: Executive Summary. New York, NY: Schulman, Ronca, and Bucuvalas Inc; 2001:1-20.
⁵ BI data on file
⁶ Singh D, Ferguson GT, Bolitschek J, et al. Tiotropium+olodaterol shows clinically meaningful improvements in quality of life. Res Med 2015 DOI: http://dx.doi.org/10.1016/j.rmed.2015.08.002 (in press)
⁷ Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD. 2015. Available from: http://www.goldcopd.org/ [Last accessed August 2015]
⁸ Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014; 371 (14): 1285-94.
⁹ Buhl R, Maltais F, Abrahams R, et al. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD2-4). Eur Respir J 2015; 45(4):969-79.
¹⁰ Ferguson GT, Flezar M, Korn S, et al. Efficacy of tiotropium + olodaterol in patients with COPD by initial disease severity and treatment intensity. Adv Ther 2015; 32(6): 523–36.
¹¹ BI data on file.
¹² Ferguson GT, Feldman GJ, Hofbauer P, et al. Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2–4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014;9:629-45.
¹³ Newman SP, Brown J, Steed KP, Reader SJ, Kladders H. Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: Comparison of Respimat® with conventional metered-dose inhalers with and without spacer devices. Chest 1998;113:957-63.
¹⁴ Pitcairn G, Reader S, Pavia D, Newman S. Deposition of corticosteroid aerosol in the human lung by Respimat® Soft Mist™ Inhaler compared to deposition by metered dose inhaler or by Turbuhaler® dry powder inhaler. J Aerosol Med 2005; 18(3):264-72.
¹⁵ Peterson JB, Prisk GK, Darquenne C. Aerosol deposition in the human lung periphery is increased by reduced-density gas breathing. J Aerosol Med Pulm Drug Deliv. 2008; 21(2):159–68.
¹⁶ Dalby R, Spallek M, Voshaar T. A review of the development of Respimat® Soft Mist™ Inhaler. Int J Pharm 2004; 283: 1-9.
¹⁷ Zierenberg B. Optimising the in vitro performance of the Respimat®. J Aerosol Med 1999; 12 (Suppl 1): S19-24.
¹⁸ Dalby RN, Eicher J, Zierenberg B. Development of Respimat® SoftMist™ inhaler and its clinical utility in respiratory disorders. Med Devices (Auckl) 2011; 4: 145-55.
¹⁹ Anderson P. Use of Respimat Soft Mist Inhaler in COPD patients. Int J Chron Obstruct Pulmon Dis.  2006;1(3): 251–59.
²⁰ WHO. Global Alliance Against Chronic Respiratory Diseases. Chronic Respiratory Diseases. http://www.who.int/gard/publications/chronic_respiratory_diseases.pdf [Last accessed June 2015]
²¹ WHO. Chronic respiratory diseases, Burden of COPD. http://www.who.int/respiratory/copd/burden/en/index.html.
²² Casaburi R. Activity promotion: a paradigm shift for chronic obstructive pulmonary disease therapeutics. Am Thorac Soc 2011; 8(4):334-37.

MEDIA CONTACT

Dr. Kristin Jakobs

Media & PR
Phone +49 6132 77 144553
Mobile +49 151 6894 7444
Fax +49 6132 77 6601
e-mail

###

Boehringer Ingelheim: new data from two trials showing Spiolto® Respimat® provides significant quality of life improvements in patients with moderate to severe COPD