- New data showed positive effect of nintedanib on slowing decline of lung function in a broad range of fibrosing interstitial lung diseases with a progressive phenotype1
- Phase III results published in the New England Journal of Medicine and to be presented at the European Respiratory Society (ERS) International Congress in Madrid, Spain
- Regulatory applications were recently submitted for this new indication with the FDA and EMA
INGELHEIM, Germany I September 30, 2019 I Boehringer Ingelheim announced today that in the Phase III INBUILD® trial nintedanib slowed lung function decline by 57% across the overall study population, as assessed by the annual rate of decline in forced vital capacity (FVC)a over 52 weeks in patients with fibrosing interstitial lung disease (ILDs) with signs of progression.1 Just published in the New England Journal of Medicine and to be presented at the ERS Congress in Madrid, Spain, the study has met its primary endpoint and demonstrated the efficacy and safety of nintedanib in patients with a broad range of progressive fibrosing interstitial lung diseases other than idiopathic pulmonary fibrosis (IPF).1 Chronic hypersensitivity pneumonitis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD (SSc-ILD), mixed connective tissues disease-associated ILD, sarcoidosis and idiopathic forms of interstitial pneumonias, i.e. non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia, are among these diseases. Nintedanib was shown to slow the rate of ILD progression independent of the fibrotic pattern seen on chest imaging.1 The side effect profile was consistent with previous studies of nintedanib in ILDs, with diarrhoea being the most common adverse event.1
About the study
INBUILD® is the first clinical trial in the field of ILDs to group patients based on the clinical behaviour of their disease, rather than the primary clinical diagnosis.1 ILDs encompass a large group of more than 200 disorders that may involve the threat of pulmonary fibrosis – an irreversible scarring of lung tissue that negatively impacts lung function.2 Patients with ILD can develop a progressive phenotype that causes pulmonary fibrosis, leading to lung function decline, deterioration in quality of life and early mortality similar to IPF, the most frequent form of idiopathic interstitial pneumonias.3 The course of the disease and the symptoms are similar in progressive fibrosis ILDs regardless of the underlying disease.4
In the INBUILD® trial, nintedanib slowed lung function decline by 57% across the overall study population, with an adjusted annual rate of decline over 52 weeks in FVC of -80.8 mL/year compared to -187.8 mL/year for placebo (difference, 107.0 mL/year [95% CI, 65.4 to 148.5]; p<0.001).1 Ofev demonstrated a consistent effort on lung function decline in patients with an usual interstitial pneumonia (UIP) like fibrotic pattern and those with other fibrotic patterns on HRCT.1 The most common adverse event was diarrhoea, reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively.1 The safety profile observed in INBUILD® was consistent to what has been seen in IPF and SSc-ILD patients treated with nintedanib previously.1
Implications for the ILD community
“Progressive fibrosis of the lung can have a devastating impact on patients with a range of conditions. Yet, except for IPF and the new approved therapy for use in SSc-ILD in the U.S., there are currently no medications approved for the treatment of progressive fibrosing ILDs,” explained Professor Kevin Flaherty, M.D., Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan in Ann Arbor, Michigan, U.S., and lead investigator of the INBUILD® trial. “The results of INBUILD showed for the first time that nintedanib slowed the decline of lung function in patients with a range of fibrosing lung diseases, who demonstrate a progressive phenotype, across a spectrum of ILD diagnoses.”
“We are very proud to be presenting the results of this first ever clinical trial studying patients with different forms of progressive fibrosing ILDs, which are the basis of the regulatory applications that were recently submitted with the FDA and EMA,” commented Dr. Mehdi Shahidi, M.D., Chief Medical Officer, Boehringer Ingelheim. “We are absolutely committed to improving the lives of people living with pulmonary fibrosis, in particular those affected by rare diseases with a high level of unmet need.”
a FVC is Forced Vital Capacity, an established measure of lung function
The INBUILD® trial1
The INBUILD® trial was a randomised, double-blind, placebo-controlled, parallel group trial conducted at 153 sites in 15 countries that evaluated the efficacy, safety, and tolerability of nintedanib (150 mg, 2 x daily) over 52 weeks in patients with progressive fibrosing interstitial lung disease. Eligible patients were aged ≥ 18 years with a physician-diagnosed ILD other than IPF and features of fibrosing lung disease of >10% extent in high-resolution computed tomography (HRCT). Patients were required to meet criteria for ILD progression within 24 months before screening, based on decline in FVC, increased fibrotic changes on imaging, or worsening of symptoms, despite treatment with drugs commonly used in clinical practice to treat ILD.
A total of 663 patients, of whom 412 (62.1%) had a usual interstitial pneumonia (UIP) fibrotic pattern on HRCT, were randomised 1:1 to receive oral nintedanib 150 mg twice daily or placebo. The primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. 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 fibrosis progresses, lung function gradually and irreversibly deteriorates. Main secondary endpoints were absolute change from baseline in King’s Brief Interstitial Lung Disease (K-BILD) questionnaire total score at week 52, time to first acute exacerbation of ILD or death over 52 weeks; and time to death over 52 weeks. An acute exacerbation is a sudden clinically significant deterioration in respiratory function, in many cases with unknown cause, which negatively impacts the disease course and often leads to death.
Progressive fibrosing interstitial lung disease
The course of the disease and the symptoms are similar in progressive fibrosing interstitial lung diseases regardless of the underlying condition.4 There is an accelerated loss of lung function, a deterioration in quality of life and the disease is associated with a poor prognosis.3
The progressive fibrosis of the lung leads to an irreversible loss of lung function and is associated with high morbidity and mortality. On average, 18-32% of patients with ILD might develop a progressive pulmonary fibrosis.5 Progressive fibrosing interstitial lung diseases encompass a range of clinical diagnoses, including: hypersensitivity pneumonitis, sarcoidosis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, mixed connective tissues disease-associated ILD, idiopathic non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia amongst others.3
Patients with progressive fibrosing interstitial lung diseases are a neglected patient population for whom no approved treatment options exist that effectively influence the course of their disease.6 Therapy of progressive fibrosing interstitial lung diseases is therefore a challenge that requires interdisciplinary care, especially by pulmonologists and rheumatologists.3
Nintedanib
Nintedanib is already approved in more than 70 countries for the treatment of patients living with idiopathic pulmonary fibrosis (IPF) – a chronic and ultimately fatal disease characterised by a decline in lung function. It is estimated that over 80,000 people with IPF have been treated with nintedanib.
Nintedanib is one of two antifibrotic drugs shown to slow the disease progression in IPF, and they are approved and recommended for use in IPF patients by international guidelines.6
In September 2019, nintedanib was approved in the U.S. as the first and only therapy to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD. Submissions have been made to other major regulatory bodies across the globe.
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
a FVC is Forced Vital Capacity, an established measure of lung function
References
1 Flaherty K, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases N Eng J Med. Published 29 September, 2019. NEJM.org. DOI: 10.1056/NEJMoa1908681
2 British Lung Foundation. What is pulmonary fibrosis? Available at: https://www.blf.org.uk/support-for-you/pulmonary-fibrosis/what-is-pulmonary-fibrosis [Accessed September 2019].
3 Cottin V, Hirani NA, Hotchkin DL, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018;27(150):pii:180076.
4 Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respiratory Research 2019:20:57.
5 Wijsenbeek M, Kreuter M, Fischer A, et al. Non-IPF progressive fibrosing interstitial lung disease (PF-ILD): the patient journey. Am J Respir Crit Care Med 2018;197:A1678.
6 Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res 2017;4(1):e000212.
SOURCE: Boehringer Ingelheim
Post Views: 112
- New data showed positive effect of nintedanib on slowing decline of lung function in a broad range of fibrosing interstitial lung diseases with a progressive phenotype1
- Phase III results published in the New England Journal of Medicine and to be presented at the European Respiratory Society (ERS) International Congress in Madrid, Spain
- Regulatory applications were recently submitted for this new indication with the FDA and EMA
INGELHEIM, Germany I September 30, 2019 I Boehringer Ingelheim announced today that in the Phase III INBUILD® trial nintedanib slowed lung function decline by 57% across the overall study population, as assessed by the annual rate of decline in forced vital capacity (FVC)a over 52 weeks in patients with fibrosing interstitial lung disease (ILDs) with signs of progression.1 Just published in the New England Journal of Medicine and to be presented at the ERS Congress in Madrid, Spain, the study has met its primary endpoint and demonstrated the efficacy and safety of nintedanib in patients with a broad range of progressive fibrosing interstitial lung diseases other than idiopathic pulmonary fibrosis (IPF).1 Chronic hypersensitivity pneumonitis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD (SSc-ILD), mixed connective tissues disease-associated ILD, sarcoidosis and idiopathic forms of interstitial pneumonias, i.e. non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia, are among these diseases. Nintedanib was shown to slow the rate of ILD progression independent of the fibrotic pattern seen on chest imaging.1 The side effect profile was consistent with previous studies of nintedanib in ILDs, with diarrhoea being the most common adverse event.1
About the study
INBUILD® is the first clinical trial in the field of ILDs to group patients based on the clinical behaviour of their disease, rather than the primary clinical diagnosis.1 ILDs encompass a large group of more than 200 disorders that may involve the threat of pulmonary fibrosis – an irreversible scarring of lung tissue that negatively impacts lung function.2 Patients with ILD can develop a progressive phenotype that causes pulmonary fibrosis, leading to lung function decline, deterioration in quality of life and early mortality similar to IPF, the most frequent form of idiopathic interstitial pneumonias.3 The course of the disease and the symptoms are similar in progressive fibrosis ILDs regardless of the underlying disease.4
In the INBUILD® trial, nintedanib slowed lung function decline by 57% across the overall study population, with an adjusted annual rate of decline over 52 weeks in FVC of -80.8 mL/year compared to -187.8 mL/year for placebo (difference, 107.0 mL/year [95% CI, 65.4 to 148.5]; p<0.001).1 Ofev demonstrated a consistent effort on lung function decline in patients with an usual interstitial pneumonia (UIP) like fibrotic pattern and those with other fibrotic patterns on HRCT.1 The most common adverse event was diarrhoea, reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively.1 The safety profile observed in INBUILD® was consistent to what has been seen in IPF and SSc-ILD patients treated with nintedanib previously.1
Implications for the ILD community
“Progressive fibrosis of the lung can have a devastating impact on patients with a range of conditions. Yet, except for IPF and the new approved therapy for use in SSc-ILD in the U.S., there are currently no medications approved for the treatment of progressive fibrosing ILDs,” explained Professor Kevin Flaherty, M.D., Professor of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan in Ann Arbor, Michigan, U.S., and lead investigator of the INBUILD® trial. “The results of INBUILD showed for the first time that nintedanib slowed the decline of lung function in patients with a range of fibrosing lung diseases, who demonstrate a progressive phenotype, across a spectrum of ILD diagnoses.”
“We are very proud to be presenting the results of this first ever clinical trial studying patients with different forms of progressive fibrosing ILDs, which are the basis of the regulatory applications that were recently submitted with the FDA and EMA,” commented Dr. Mehdi Shahidi, M.D., Chief Medical Officer, Boehringer Ingelheim. “We are absolutely committed to improving the lives of people living with pulmonary fibrosis, in particular those affected by rare diseases with a high level of unmet need.”
a FVC is Forced Vital Capacity, an established measure of lung function
The INBUILD® trial1
The INBUILD® trial was a randomised, double-blind, placebo-controlled, parallel group trial conducted at 153 sites in 15 countries that evaluated the efficacy, safety, and tolerability of nintedanib (150 mg, 2 x daily) over 52 weeks in patients with progressive fibrosing interstitial lung disease. Eligible patients were aged ≥ 18 years with a physician-diagnosed ILD other than IPF and features of fibrosing lung disease of >10% extent in high-resolution computed tomography (HRCT). Patients were required to meet criteria for ILD progression within 24 months before screening, based on decline in FVC, increased fibrotic changes on imaging, or worsening of symptoms, despite treatment with drugs commonly used in clinical practice to treat ILD.
A total of 663 patients, of whom 412 (62.1%) had a usual interstitial pneumonia (UIP) fibrotic pattern on HRCT, were randomised 1:1 to receive oral nintedanib 150 mg twice daily or placebo. The primary endpoint was the annual rate of decline in FVC (mL/year) assessed over 52 weeks. 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 fibrosis progresses, lung function gradually and irreversibly deteriorates. Main secondary endpoints were absolute change from baseline in King’s Brief Interstitial Lung Disease (K-BILD) questionnaire total score at week 52, time to first acute exacerbation of ILD or death over 52 weeks; and time to death over 52 weeks. An acute exacerbation is a sudden clinically significant deterioration in respiratory function, in many cases with unknown cause, which negatively impacts the disease course and often leads to death.
Progressive fibrosing interstitial lung disease
The course of the disease and the symptoms are similar in progressive fibrosing interstitial lung diseases regardless of the underlying condition.4 There is an accelerated loss of lung function, a deterioration in quality of life and the disease is associated with a poor prognosis.3
The progressive fibrosis of the lung leads to an irreversible loss of lung function and is associated with high morbidity and mortality. On average, 18-32% of patients with ILD might develop a progressive pulmonary fibrosis.5 Progressive fibrosing interstitial lung diseases encompass a range of clinical diagnoses, including: hypersensitivity pneumonitis, sarcoidosis, autoimmune ILDs such as rheumatoid arthritis-associated ILD, systemic sclerosis-associated ILD, mixed connective tissues disease-associated ILD, idiopathic non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia amongst others.3
Patients with progressive fibrosing interstitial lung diseases are a neglected patient population for whom no approved treatment options exist that effectively influence the course of their disease.6 Therapy of progressive fibrosing interstitial lung diseases is therefore a challenge that requires interdisciplinary care, especially by pulmonologists and rheumatologists.3
Nintedanib
Nintedanib is already approved in more than 70 countries for the treatment of patients living with idiopathic pulmonary fibrosis (IPF) – a chronic and ultimately fatal disease characterised by a decline in lung function. It is estimated that over 80,000 people with IPF have been treated with nintedanib.
Nintedanib is one of two antifibrotic drugs shown to slow the disease progression in IPF, and they are approved and recommended for use in IPF patients by international guidelines.6
In September 2019, nintedanib was approved in the U.S. as the first and only therapy to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated ILD. Submissions have been made to other major regulatory bodies across the globe.
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
a FVC is Forced Vital Capacity, an established measure of lung function
References
1 Flaherty K, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases N Eng J Med. Published 29 September, 2019. NEJM.org. DOI: 10.1056/NEJMoa1908681
2 British Lung Foundation. What is pulmonary fibrosis? Available at: https://www.blf.org.uk/support-for-you/pulmonary-fibrosis/what-is-pulmonary-fibrosis [Accessed September 2019].
3 Cottin V, Hirani NA, Hotchkin DL, et al. Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 2018;27(150):pii:180076.
4 Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respiratory Research 2019:20:57.
5 Wijsenbeek M, Kreuter M, Fischer A, et al. Non-IPF progressive fibrosing interstitial lung disease (PF-ILD): the patient journey. Am J Respir Crit Care Med 2018;197:A1678.
6 Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res 2017;4(1):e000212.
SOURCE: Boehringer Ingelheim
Post Views: 112
