New analysis suggests nintedanib* may reduce mortality in patients with idiopathic pulmonary fibrosis

• Pooled analysis of data from Phase II and III nintedanib* trials show positive trend toward reduced mortality in patients with idiopathic pulmonary fibrosis (IPF)¹
• Findings reflect that nintedanib* slows disease progression in patients with IPF²

BURLINGTON, ON, Sept. 25, 2014 /CNW/ - A pooled analysis of data from the two replicate Phase III INPULSIS™ trials, and the Phase II TOMORROW trial, presented September 24 at the 18th International Colloquium on Lung and Airway Fibrosis (ICLAF), show a positive trend toward a reduction in all-cause and respiratory mortality in patients with idiopathic pulmonary fibrosis (IPF) who were treated with nintedanib*.¹ IPF is a debilitating and fatal lung disease associated with high mortality. Over 52 weeks, the results of the pooled analysis showed:¹

• A 30% relative risk reduction in all-cause mortality with nintedanib* vs. placebo (5.8% vs. 8.3%)
• A 38% relative risk reduction in respiratory mortality with nintedanib* vs. placebo (3.6% vs. 5.7%)

Although all-cause and respiratory mortality were secondary endpoints in the TOMORROW and INPULSIS™ trials, none of these trials were powered to show a difference between nintedanib* and placebo. The retrospective pooled analysis was undertaken to understand more precisely the effect of nintedanib* treatment on mortality.

Analyses of the pooled INPULSIS™ trials show that nintedanib* consistently slowed disease progression by significantly reducing the annual rate of decline in FVC compared with placebo.³ It also slowed lung function decline even in the presence of emphysema that had been identified by high-resolution CT (HRCT) at baseline.⁴

"Clinical trials of nintedanib* have consistently found that it slows disease progression for patients with IPF. This new analysis shows it may reduce mortality as well," said Dr. Martin Kolb, Director of Respirology and Research Director, Firestone Institute for Respiratory Health, and Associate Professor of Medicine, McMaster University. "This is encouraging news, as treating this deadly disease can be a challenge; more effective treatments are needed."

About 50 per cent of people with IPF die within two to three years of diagnosis.⁵ It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing.⁶ Currently, there are very few treatment options.

Nintedanib*, one 150 mg capsule twice a day, has been shown to slow disease progression by reducing the annual rate of decline in lung function by 50 per cent in a broad range of IPF patient types, also including patients with early disease (FVC>90% predicted), no honeycombing on HRCT and/or concomitant emphysema.² 

* Nintedanib is an investigational compound. Its safety and efficacy has not yet been fully established and it is currently not authorized for sale in Canada.

Notes to Editor
Unmet Need in IPF
IPF is a chronic, progressive, severely debilitating and ultimately fatal lung disease for which there are limited treatment options.^5,7 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.^8,9  From the time of diagnosis the median survival rate is approximately two to three years.⁵

IPF is characterized by progressive scarring of lung tissue and results in loss of lung function over time.^10,11 Development of scar tissue is called fibrosis, which leads to impaired gas exchange and insufficient oxygen transport to vital organs.^10,11 As a result, individuals with IPF may experience shortness of breath, cough and often have difficulty participating in everyday physical activities.¹¹ The average IPF patient has an annual lung function loss, measured by forced vital capacity (FVC), of 150–200mL.¹²

"This analysis is promising and welcome news for patients with IPF," said Robert Davidson, Founder, Canadian Pulmonary Fibrosis Foundation. "IPF is a devastating illness – every breath can be a struggle. We look forward to new treatments on the horizon that will provide new hope for Canadians with IPF."

About the INPULSIS™ trials
The double blind, randomized and placebo-controlled trials, involving 1,066 patients across 24 countries, 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.^2,13

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) and time to first acute exacerbation. Other secondary endpoints included absolute change from baseline in FVC (mL and % predicted), overall survival, respiratory mortality, on-treatment survival.²

About the TOMORROW trial
The Phase II TOMORROW trial was a 12-month, randomized, double-blind, placebo-controlled trial conducted at 92 sites in 25 countries.¹⁴ The trial evaluated the safety and efficacy of oral nintedanib* at four dosage levels in 432 patients diagnosed with IPF, consistent with the criteria published by the American Thoracic Society (ATS) and European Respiratory Society (ERS).^5,2

The primary endpoint for the TOMORROW trial was annual rate of decline in forced vital capacity (FVC).² Key secondary end points included the changes from baseline in FVC and DL_CO; the total score on the St. George's Respiratory Questionnaire (SGRQ); the incidence of acute exacerbations. Other secondary endpoints included; the distance achieved on the 6-minute walk test; survival; and death from a respiratory cause.^14,15

About nintedanib*
Nintedanib* is an investigational small molecule tyrosine kinase inhibitor (TKI) in development by Boehringer Ingelheim for idiopathic pulmonary fibrosis (IPF).² 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).^2,16 By blocking the signaling 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.^2,17 

About Boehringer Ingelheim (Canada) Ltd.
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.

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.

*Nintedanib is an investigational compound. Its safety and efficacy have not yet been fully established. 

References:

¹ Richeldi L et al. Pooled analysis of mortality data from the TOMORROW and INPULSIS™ trials of nintedanib in idiopathic pulmonary fibrosis (IPF). Oral presentation at: 18th International Colloquium on Lung and Airway Fibrosis (ICLAF); 2014 September 20-24, Quebec, Canada.
² Richeldi L, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014 May; 370(22):2071-82.
³ Costabel U, et al. Pre-specified subgroup analyses of pooled data from the INPULSIS™ trial of nintedanib in idiopathic pulmonary fibrosis. Poster presentation at the ICLAF congress, September 2014.
⁴ Cottin V, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS™ trials. Poster presentation at the ICLAF congress, September 2014.
⁵ Raghu G, 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.
⁶ Collard H, et al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2007;176:636–643.
⁷ Woodcock HV. Molyneaux PL. Maher TM. Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib. Drug Design, Development and Therapy 2013; 7:503-510.
⁸ Statistics Canada. Population of Canada. Available at http://www.statcan.gc.ca/start-debut-eng.html. Accessed March 2014.
⁹ Raghu 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.
¹⁰ NHLBI. What Is Idiopathic Pulmonary Fibrosis? Available at nhlbi.nih.gov/health/health-topics/topics/ipf/. Accessed April 2014.
¹¹ The Lung Association. Idiopathic Pulmonary Fibrosis. Available at http://www.lung.ca/diseases-maladies/a-z/ipf-pfi/index_e.php. Accessed March 2014.
¹² Ley. et al. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011;183:431–440.
¹³ Richeldi L, et al. Design of the INPULSIS™ Trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med 2014 Jul; 108 (7):1023-30.
¹⁴ Richeldi L et al. Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis. N Engl J Med. Sept 2011. Vol. 365 No. 12: 1079-1087
¹⁵ Jones PW, et al The St George's Respiratory Questionnaire. Respir Med September 1991; 85(Suppl B):25-31; discussion 33-7.
¹⁶ Hilberg F. et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
¹⁷ 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.

For further information: please visit www.boehringer-ingelheim.ca