New analysis confirms OFEV® (nintedanib) slows disease progression in IPF and reduces risk of acute exacerbations 

  • Pooled data from three key studies confirms that OFEV® slows disease progression by approximately 50% as measured by decline in forced vital capacity (FVC)*1-8
  • The pooled analysis also demonstrated that OFEV® significantly reduced the risk of acute exacerbations by 47%1
  • OFEV® reduced the risk of all-cause mortality by 30% and significantly reduced on-treatment mortality by 43%**1,9,10 

Ingelheim, Germany, February 25, 2016 – Pooled analysis from the TOMORROW and INPULSIS® trials, recently published in Respiratory Medicine, provides further evidence that OFEV® (nintedanib) significantly reduces the risk of acute exacerbations by 47% in people with idiopathic pulmonary fibrosis (IPF), a debilitating and life-threatening lung disease.1 An acute exacerbation, a sudden worsening in respiratory function without warning or known cause, is a leading cause of hospitalisation for people with IPF.11 Around half of all people hospitalised because of an acute IPF exacerbation die during hospitalisation.12 The findings also showed that OFEV® reduced the risk of death,1,9,10 and slowed disease progression by approximately 50% across a broad range of patient types***.1-8 

The pooled analysis is based on data from the Phase II TOMORROW trial and the two Phase III INPULSIS® trials that included a total of 1,231 people with IPF (723 treated with OFEV®, 508 treated with placebo).1 Data from these three clinical trials formed the basis for the approval of OFEV® in the United States, Europe, Japan and other countries worldwide.

The one-year combined data showed that:1
•    OFEV® significantly reduced the risk of an acute IPF exacerbation as reported by treating physicians by 47%, compared to placebo. 
•    Fewer people overall experienced an acute exacerbation. The proportion of people with at least one acute exacerbation was 4.6% in the OFEV® group and 8.7% in the placebo group. 

Professor Luca Richeldi, Professor of Respiratory Medicine at the University of Southampton, United Kingdom"Reducing the risk of exacerbations is an important treatment goal in the management of idiopathic pulmonary fibrosis because of their unpredictability and devastating impact on the course of the disease. Acute exacerbations often lead to death within a few months,” said Professor Luca Richeldi, Professor of Respiratory Medicine at the University of Southampton, United Kingdom. “Analyses like these add to the growing body of evidence that we may see people with IPF live longer because recently approved treatments have an impact on the course of the disease.”

Over the one-year period of the studies, OFEV® also showed a favourable trend in all survival endpoints:
•    Compared to placebo, patients taking OFEV® had a 30% reduction in the risk of dying from any cause** (p=0.0954).1
•    Patients taking OFEV® also had a 43% reduced risk of dying while on treatment (on-treatment mortality) (p=0.0274).1,9,10 
•    A 38% reduction in the risk of death because of an exacerbation or other respiratory cause versus placebo (p=0.0779) could also be seen.1

The analysis also confirmed that OFEV® slowed disease progression by approximately 50%, as measured by annual rate of decline in forced vital capacity (FVC). The overall adjusted annual rate of decline in FVC was −112.4 mL/year with OFEV® and −223.3 mL/year with placebo (difference: 110.9 mL/year), confirming the beneficial effect of OFEV® on slowing disease progression. The safety and tolerability profile of OFEV® in the pooled analysis was consistent with safety results of the individual TOMORROW and INPULSIS® trials, with diarrhoea being the most frequently reported adverse event.1

“The analysis from three key trials with similar designs further confirms the benefits of OFEV® in reducing mortality and acute exacerbations in idiopathic pulmonary fibrosis. These are important considerations in the management of IPF, and we believe that these new data will help guide therapy discussions between physicians and their patients,” said Dr. William Mezzanotte, Therapeutic Area Head, Respiratory Medicine. 

Notes to Editor

About the TOMORROW and INPULSIS® trials with OFEV1
Period 1 of the TOMORROW trial was a randomised, placebo-controlled, 52-week, Phase II dose-finding trial of OFEV® in patients with IPF, which showed that OFEV® 150 mg twice daily was associated with a reduced rate of decline in forced vital capacity (FVC), fewer investigator-reported acute exacerbations, and preservation of health-related quality of life measured using the St George’s Respiratory Questionnaire (SGRQ). The INPULSIS trials were two replicate, randomised, placebo-controlled Phase III trials that assessed the efficacy and safety of 52 weeks’ treatment with OFEV® 150 mg twice daily in patients with IPF. The primary endpoint in the INPULSIS trials was the annual rate of decline in FVC; key secondary endpoints were time to first investigator-reported acute exacerbation and change from baseline in SGRQ total score, both over 52 weeks. 

A total of 1,231 patients were included in the pooled analysis of the TOMORROW and INPULSIS trials (723 treated with OFEV®, 508 treated with placebo). 

The favourable risk-benefit profile of OFEV® was reinforced, with the treatment demonstrating an acceptable safety and tolerability profile.

About OFEV® (nintedanib)
OFEV® is a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim for IPF.13 OFEV®, one capsule twice a day, slows disease progression by reducing the annual rate of decline in lung function by 50% in a broad range of IPF patient types***1-8 This includes patients with early disease (FVC >90% pred),4 limited radiographic fibrosis (no honeycombing) on high resolution computed tomography (HRCT)5 and those with emphysema6 Side effects with OFEV® can be effectively managed in most patients.2

OFEV® targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly OFEV® inhibits platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR).2,14,15 It is believed that OFEV® reduces disease progression in IPF and slows the decline in lung function by blocking the signalling pathways that are involved in fibrotic processes.2,15,16

About idiopathic pulmonary fibrosis
IPF is a progressive and life threatening lung disease.17 IPF affects as many as 14-43 people per 100,000 worldwide.18,19 IPF is characterised by progressive scarring of lung tissue and loss of lung function over time.14,20 Development of scarred tissue is called fibrosis. Over time, as the tissue thickens and stiffens with scarring, the lungs lose their ability to take in and transfer oxygen into the bloodstream and vital organs do not get enough oxygen.21 As a result, individuals with IPF experience shortness of breath, a non-productive cough and often have difficulty participating in everyday physical activities.21 All patients with IPF are at risk of acute IPF exacerbations.22 Defined as rapid deteriorations of symptoms within days or weeks, these events can occur at any point in the course of the disease, even at first presentation.22 

For further information regarding IPF please visit the Boehringer Ingelheim News Centre
 

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

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.

Footnotes

*   Lung function decline measured by forced vital capacity (FVC)
**  On-treatment mortality was defined as deaths recorded during the 52-week study period and 28-day follow-up
*** Including those with preserved lung function (FVC>90%pred), no honeycombing on HRCT and concomitant emphysema

Referências

1.    Richeldi L, et al. Pooled analysis of data from the TOMORROW and INPULSIS® trials. Resp Med 02/2016. DOI: 10.1016/ j.rmed.2016.02.001. Available at: http://www.resmedjournal.com/article/S0954-6111(16)30019-1/abstract
2.    Richeldi L, du Bois RM, Raghu G, et al; for the INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;380(22):2071-2082
3.    OFEV® Summary of Product Characteristics. Boehringer Ingelheim International GmbH. January 2016.
4.    Kolb M, Richeldi L, Kimura T, Stowasser S, Hallmann C, du Bois RM. Effect of baseline FVC on decline in lung function with nintedanib in patients with IPF: results from the INPULSIS® trials. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
5.    Raghu G, Wells A, Nicholson AG, et al. Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS® trials in IPF. Poster presented at the 110th American Thoracic Society Conference; Denver, Colorado, May 15–20, 2015.
6.    Cottin V, Taniguchi H, Richeldi L, et al. Effect of baseline emphysema on reduction in FVC decline with nintedanib in the INPULSIS® trials. Abstract presented at the 18th International Colloquium on Lung and Airway Fibrosis; Mont Tremblant, Canada, September 20-24, 2014. Available at: http://iclaf.com/conference/index.php/2014/ICLAF/paper/view/151. Accessed [February 2016].
7.    Costabel U., et al. Efficacy of nintedanib in idiopathic pulmonary fibrosis across pre-specified subgroups in INPULSIS®. AJRCCM. 2015; 15-10031.
8.    Keating GM. Nintedanib: A Review of Its Use in Patients with Idiopathic Pulmonary Fibrosis. Drugs. 2015 Jul;75(10):1131-40. doi: 10.1007/s40265-015-0418-6.
9.    Data on file. Boehringer Ingelheim International: Kirsten AM, et al. Pooled analysis of mortality data from the TOMORROW and INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis (IPF). Poster presented at 56th Congress of the German Respiratory Society; Berlin, Germany. March 18-21 2015.
10.    Cottin V. Nintedanib: a new treatment for idiopathic pulmonary fibrosis. Clinical Investigation 05/2015; DOI: 10.4155/cli.15.27
11.    Kubo H, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005, 128:1475–1482.
12.    Kim D. S., Acute exacerbations in patients with idiopathic pulmonary fibrosis. Respir Res. 2013;14:86
13.    Song JW, et al. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J. 2011;37:356-363.
14.    Selman M, et al. Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy. Ann Intern Med. 2001;134:136-51.
15.    Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
16.    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.
17.    Ley B., et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. AJRCCM. 2011;183:431–40.
18.    Raghu G, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174:810-816.
19.    Fernández Pérez E, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: a population-based study. Chest. 2010;137:129-37.
20.    NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/. Accessed [February 2016].
21.    Pulmonary Fibrosis Foundation. Symptoms. Available at: http://www.pulmonaryfibrosis.org/life-with-pf/about-pf. Accessed [February 2016].
22.    Collard H, et al. Acute Exacerbations of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2007;176:636–643.