Study findings show nintedanib* slows progression of Idiopathic Pulmonary Fibrosis (IPF), a debilitating and fatal lung disease

• Phase III Idiopathic Pulmonary Fibrosis (IPF) results published in NEJM show nintedanib* slows disease progression by reducing annual decline in lung function by approximately 50 per cent¹
• Nintedanib* is the first targeted IPF treatment to consistently meet the primary endpoint in two identically designed international Phase III trials

BURLINGTON, ON, May 20, 2014 /CNW/ - Results from the Phase III INPULSIS™ trials, recently published online in the New England Journal of Medicine (NEJM), show nintedanib* significantly slowed disease progression in patients with idiopathic pulmonary fibrosis (IPF).¹

NINTEDANIB SIGNIFICANTLY REDUCES LUNG FUNCTION DECLINE
In the two 52 week INPULSIS™ trials, involving 1,066 patients, nintedanib* significantly reduced the annual decline in FVC by approximately 50 per cent compared to patients taking placebo. The annual rate of FVC decline in the two trials was:¹

• INPULSIS™-1: -114.7mL (nintedanib*) vs. -239.9mL (placebo)
• INPULSIS™-2: -113.6mL (nintedanib*) vs. -207.3mL (placebo)

In INPULSIS™-1, there was no statistically significant difference between the nintedanib* and placebo groups in the key secondary endpoints.¹

Both key secondary endpoints were met in the INPULSIS™ - 2 trial. There was significantly less deterioration in quality of life (measured by the St. George's Respiratory Questionnaire) and a reduced risk of a first acute exacerbation in patients taking nintedanib* versus placebo.¹

In both trials, the most common adverse events were gastrointestinal in nature, of mild to moderate intensity, generally manageable, rarely leading to discontinuation of treatment.¹

The most frequent adverse event in the nintedanib groups was diarrhea, which was reported in 62 per cent vs. 19 per cent (INPULSIS™-1) and 63 per cent vs. 18 per cent (INPULSIS™-2) of patients in the nintedanib* vs. placebo, respectively. Less than five per cent of those who experienced diarrhea in the nintedanib* groups of INPULSIS™-1 and INPULSIS™-2 discontinued treatment due to this event.¹

The proportion of patients with serious adverse events was similar in all groups.

"Patients with IPF currently have very limited treatment options and there is a high unmet need for effective therapies that can alter the course of this deadly disease by slowing its progression," said Dr. Martin Kolb, Director of Respirology at McMaster University and the Firestone Institute for Respiratory Health at St. Joseph's Healthcare. "Results from this trial are very promising because for the first time we have a drug that has consistently met its primary endpoints in two large phase III trials."

UNMET NEED IN IPF
IPF is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are limited treatment options.^2,3 Currently, the number of individuals living with IPF is unknown, but it is estimated that between 5,000 to 15,000 Canadians have the disease.⁴,⁵ From the time of diagnosis the median survival rate is approximately two to three years.²

IPF is characterized by progressive scarring of lung tissue and results in loss of lung function over time.^6,7 Development of scar tissue is called fibrosis, which leads to impaired gas exchange and insufficient oxygen transport to vital organs.^6,7 As a result, individuals with IPF may experience shortness of breath, cough and often have difficulty participating in everyday physical activities.⁷

The average IPF patient has an annual lung function loss, measured by forced vital capacity (FVC), of 150–200mL.⁸

"The Canadian Pulmonary Fibrosis Foundation is pleased to see the promising study results from INPULSIS™," said Robert Davidson, Founder, Canadian Pulmonary Fibrosis Foundation. "It is our hope that new and effective treatment options will be made available to Canadians impacted by this devastating illness that literally takes your breath away."

ABOUT THE INPULSIS^TM TRIALS
The double blind, randomised and placebo-controlled trials evaluated the effect of oral nintedanib*, 150 mg twice daily, on the annual rate of decline in forced vital capacity (FVC), in patients with IPF over 52 weeks. The trials had an identical design, matched dosing, inclusion criteria, and endpoints.^9,10

The primary endpoint was the annual rate of decline in FVC (expressed in mL over 52 weeks). Key secondary endpoints were: change from baseline in health-related quality of life, as assessed by the Saint-George's Respiratory Questionnaire (SGRQ); time to first acute exacerbation (number of days). Other secondary endpoints included change from baseline in FVC, overall survival, respiratory mortality, and
on-treatment survival.^9,10

Patients included in the trials were at least 40 years of age, diagnosed with IPF within five years prior to enrolment, based on the most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) IPF guidelines for diagnosis and management.^9,10

More information can be found on clinicaltrials.gov (identifiers NCT01335464 and NCT01335477).^9,10

ABOUT NINTEDANIB*
Nintedanib* is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF).¹¹ It targets growth factor receptors, which have been shown to be potentially involved in pathomechanisms of pulmonary fibrosis, most importantly the platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).^11,12 By blocking the signalling pathways that are involved in fibrotic processes, it is believed that nintedanib* has the potential to reduce disease progression in IPF by slowing the decline of lung function.^11,13 Nintedanib* is also in clinical development as a treatment option for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.

ABOUT BOEHRINGER INGELHEIM (CANADA) LTD.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, Boehringer Ingelheim operates globally with 142 affiliates and a total of more than 47,400 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.

Taking 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 2013, Boehringer Ingelheim achieved net sales of about 14.1 billion euros. R&D expenditure corresponds to 19.5% 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.

References
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¹ Richeldi L. et al. Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis N Engl J Med. 2014; published online on May 18; DOI: 10.1056/NEJMoa1402584
² Raghu G. Collard HR. Egan JJ. et al. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011; 183:788-824.
³  Woodcock HV. Molyneaux PL. Maher TM. Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib. Drug Design, ⁴Development and Therapy 2013; 7:503-510.
Statistics Canada. Population of Canada. Available at http://www.statcan.gc.ca/start-debut-eng.html. Accessed March 2014.
⁵Raghu G. Weycker D. Edelsberg J. et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006; 174(7):810-816.
⁶  NHLBI. What Is Idiopathic Pulmonary Fibrosis? Available at nhlbi.nih.gov/health/health-topics/topics/ipf/. Accessed April 2014.
⁷  The Lung Association. Idiopathic Pulmonary Fibrosis. Available at http://www.lung.ca/diseases-maladies/a-z/ipf-pfi/index_e.php. Accessed March 2014.
⁸Ley. et al. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011;183:431–440.
⁹ NIH. Clinical Trials. Available at www.clinicaltrials.gov (NCT01335464) Accessed April 2014.
¹⁰ NIH. Clinical Trials. Available at www.clinicaltrials.gov (NCT01335477) Accessed April 2014.
¹¹Richeldi L. et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365:1079-1087.
¹² Hilberg F. et al. BIBF 1120: triple angiokinase inhibitor with sustained recptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
¹³ Wollin L. et al. Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase
Inhibitor Nintedanib in Experimental Models of Lung Fibrosis. J Pharmacol Exp Ther 2014;349:209–220.

SOURCE: Boehringer Ingelheim (Canada) Ltd.

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