Boehringer Ingelheim. (7/18/19). "Press Release: INMARK Results Suggest Prompt Treatment of IPF with Antifibrotics to Slow Disease Progression". Ingelheim.

	Organisation	Boehringer Ingelheim (Group)
	Product	Ofev®
	Product 2	clinical study_o

> INMARK® trial results published in The Lancet Respiratory Medicine1

> Treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change of the biomarker CRPM but was associated with a reduced rate of decline in forced vital capacity (FVC)1

> Patients with well-preserved lung function showed equivalent amount of decline in FVC to patients with worse baseline lung function in earlier studies1

Results from the INMARK® study, a randomised, double-blind clinical trial of Ofev® (nintedanib) vs. placebo (12 weeks) followed by an open label period (40 weeks) in patients with idiopathic pulmonary fibrosis (IPF) were published on 17 July 2019 in The Lancet Respiratory Medicine. INMARK® was the first clinical trial to investigate the predictive value of biomarkers in IPF patients treated with an antifibrotic (nintedanib). Study results reinforce the evidence that even in patients with very well-preserved lung function, a difference in forced vital capacity (FVC) decline could be demonstrated between patients treated with nintedanib and placebo over 12 weeks of treatment.1,2

IPF is a rare, debilitating and fatal lung disease which affects approximately 3 million people worldwide.3 It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and breathing difficulties.4 Due to the unpredictable nature of IPF and that the loss of lung function is irreversible, experts believe that treatment should be considered and offered to patients promptly.1,5

INMARK® assessed the rate of change in CRPM*, a biomarker that has been previously shown to be predictive of mortality in IPF, from baseline to week 12 and the proportion of subjects with disease progression defined as an absolute decline in FVC =10% predicted or death over 52 weeks.1

Treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change in CRPM but was associated with a reduced rate of decline in FVC.1

29% of the subjects in this trial experienced an FVC decline of =10% predicted or died over 52 weeks of follow-up, highlighting the progressive nature of IPF also in this population with FVC =80% predicted.

Over 12 weeks, there was a lower rate of FVC decline in patients treated with nintedanib versus placebo (5.9 (18.5) mL/12 weeks in the nintedanib group and -70.2 (13.1) mL/12 weeks in the placebo group).

“Even in this population of patients with very well-preserved lung function, a difference in FVC decline could be demonstrated between patients treated with nintedanib vs. placebo over 12 weeks of treatment. Considering the unpredictable nature of IPF and the fact that loss of lung function is irreversible the results reinforce a growing body of evidence that early treatment of IPF is the best course of action.” commented Prof Toby Maher, Consultant Respiratory Physician at the Royal Brompton Hospital in London, United Kingdom and principle investigator of the study.

Dr. Susanne Stowasser, Associate Head of Medicine Respiratory at Boehringer Ingelheim, said “Biomarker research is a key driver of modern medicine with huge impact on the understanding of health and disease states, diagnosis, drug development, and prediction of disease course or response to therapy. INMARK was the first clinical trial to investigate the predictive value of biomarkers in IPF patients treated with an antifibrotic. Being poorly understood, IPF has been subject of increasing biomarker research for years with a main focus on identifying markers for prognosis.” She added: “Pulmonary Fibrosis continue to have a devastating impact on people’s lives. Boehringer Ingelheim is committed to research such as the INMARK trial which helps our understanding of how interstitial lung diseases such as IPF progress in individual patients, and identify those who may respond best to treatment.”

Notes to Editors

About INMARK®

INMARK® included 347 patients (116 treated with nintedanib and 231 on the placebo arm) and assessed the rate of change (slope) in CRPM from baseline to week 12 (expressed in ng/mL/month), and the proportion of subjects with disease progression, defined as an absolute decline in FVC =10% predicted or death, over 52 weeks.1

Treatment with nintedanib did not affect the rate of change of blood levels of the neoepitopes CRPM over 12 weeks compared with placebo.1 Over 12 weeks, there was a lower rate of FVC decline in patients treated with nintedanib versus placebo.1 In patients who received placebo for 12 weeks, rising levels of CRPM over 12 weeks were associated with disease progression over 52 weeks.1

In this trial population, with a mean FVC at baseline of 97.5% predicted which is considered well preserved lung volume, more than a quarter of patients showed disease progression (FVC decline =10% predicted or death) over 52 weeks.1 FVC is a lung function test measuring the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. As IPF progresses, lung function gradually and irreversibly deteriorates.5 This is measured by FVC decline.

About idiopathic pulmonary fibrosis (IPF)

IPF is a rare, debilitating and fatal lung disease which affects approximately 3 million people worldwide.3 Progression of IPF is variable and unpredictable, and over time the lung function of an IPF patient gradually and irreversibly declines.4 To find out more about IPF, visit lifewithipf.com where you can access a range of materials.

About Ofev® (nintedanib)

Ofev®, a small molecule tyrosine kinase inhibitor developed by Boehringer Ingelheim researchers, is indicated in adults for the treatment of IPF.6 In 2015 Ofev® was included in the updated international treatment guidelines for IPF.7 Ofev® slows disease progression with approximately 50% reduction in the decline of lung function across a broad range of IPF patient types.8-16 Ofev® is approved in more than 70 countries for the treatment of patients living with IPF.

About Boehringer Ingelheim

Improving the health of humans and animals is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients’ lives. In animal health, Boehringer Ingelheim stands for advanced prevention.

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry’s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2018, Boehringer Ingelheim achieved net sales of around 17.5 billion euros. R&D expenditure of almost 3.2 billion euros, corresponded to 18.1 per cent of net sales.

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.

More information about Boehringer Ingelheim can be found on www.boehringer-ingelheim.com or in our annual report: http://annualreport.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

* C-reactive protein degraded by MMP-1/8 (CRPM)

References

1. Mayer TM, et al. Biomarkers of extracellular matrix turnover in patients with IPF treated with nintedanib: the INMARK study. Lancet Respir Med 2019;DOI:10.1016/S2213-2600(19)30255-3.
2. Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung function. Thorax, 2017; 72(4): 340-346.
3. Ley B, et al. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011;183(4):431-40.
4. NHLBI, NIH. What Is Idiopathic Pulmonary Fibrosis? Accessed at: www.nhlbi.nih.gov/health/health-topics/topics/ipf/ Accessed April 2017.
5. Data on file. Boehringer Ingelheim. 2016.
6. Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68:4774-4782.
7. Raghu G, et al. An Official ATS/ERS/JRS/ALAT Clinical Practice Guidelines: Treatment of Idiopathic Pulmonary Fibrosis: Executive Summary. Am J Respir Crit Care Med. 2015; 192(2)238 – 248.
8. OFEV Summary of Product Characteristics. Boehringer lngelheim International GmbH. July 2017.
9. Richeldi L, et al; for the INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Eng J Med. 2014;370(22):2071-2082.
10. Kolb M, et al. Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume. Thorax. 2016. doi:l0.1136/thoraxjnl-2016-208710.
11. Raghu G, et al. Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am Journal Respir and Critl Care Med. 2016. doi:l0.1164/rccm.201602-04020C.
12. Cottin V, 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.
13. Ryerson CJ, et al. Effect of baseline GAP index stage on decline in lung function with nintedanib in patients with idiopathic pulmonary fibrosis (IPF). Abstract presented at: the lllth American Thoracic Society Conference; San Francisco, California, May 13-18, 2016..
14. Wells A, et al. Effect of baseline composite physiologic index on benefit of nintedanib in IPF. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
15. Maher TM, et al. No effect of baseline diffusing capacity of lung for carbon monoxide on benefit of nintedanib. Abstract presented at: the European Respiratory Society International Congress; London, England, September 3-7, 2015.
16. Keating GM. Nintedanib: a review of its use in patients with idiopathic pulmonary fibrosis. Drugs. 2015;75(10):1131-1140.

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Record changed: 2023-06-05