INBUILD® study meets primary endpoint and shows that nintedanib slows lung function decline across a range of interstitial lung diseases
- New data show positive effect of nintedanib on slowing decline of lung function in a broad range of interstitial lung diseases with a progressive fibrosing phenotype 1
- Nintedanib slowed lung function decline by 57% across the overall study population 1
- Phase III results published in the New England Journal of Medicine (NEJM) and presented at the European Respiratory Society (ERS) International Congress 2019 in Madrid, Spain
- Regulatory applications were recently submitted for this new indication with the EMA and FDA
- Nintedanib is currently indicated in adults for the treatment of idiopathic pulmonary fibrosis (IPF), but is not licensed for the treatment of patients with progressive fibrosing interstitial lung disease (ILD)
Bracknell, UK, 30 September 2019: Boehringer Ingelheim announced today that the Phase III INBUILD® trial met its primary endpoint - the annual rate of decline in forced vital capacity (FVC [mL/year], an established measure of lung function) assessed over 52 weeks. Results demonstrated that nintedanib slowed lung function decline by 57% across the overall study population in patients with fibrosing ILD with evidence of progression.1 The adjusted annual rate of decline was -80.8 mL/year with nintedanib compared to -187.8 mL/year with placebo (difference: 107.0 mL/year [95% CI, 65.4 to 148.5]; P<0.001), in the overall population.1
Published in the NEJM and presented at ERS, the study demonstrated the efficacy and safety of nintedanib in patients with a broad range of progressive fibrosing ILDs other than IPF.1 These include 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 such as non-specific interstitial pneumonia, and unclassified idiopathic interstitial pneumonia.3
Nintedanib was shown to slow the annual rate of FVC decline independent of the fibrotic pattern (usual interstitial pneumonia [UIP] or non-UIP) seen on chest imaging.1 The side effect profile was consistent with previous studies of nintedanib in ILDs, with diarrhoea, vomiting and nausea being the most common adverse events in the nintedanib group.1 Liver enzyme elevations were more common in patients treated with nintedanib than placebo.1
“Progressive fibrosis of the lung is a real unmet need and can be devastating for patients. There are currently no approved medications for the treatment of non-IPF ILDs that have a progressive fibrosing phenotype,” explained Dr Nazia Chaudhuri, Consultant Respiratory Physician and Clinical Lead in ILD, Manchester University NHS Foundation Trust, and UK lead investigator of the INBUILD® trial. “The results of INBUILD are pivotal and show for the first time that nintedanib can slow down the decline of lung function in patients with a range of fibrosing lung diseases no matter what the underlying diagnosis, reinforcing the benefits of nintedanib in patients who have progressive lung fibrosis, across various ILD diagnoses.”
“We are very proud to be presenting the results of this first ever pivotal clinical trial studying patients with different forms of progressive fibrosing ILDs,” commented Dr Tim Crossman, Head of Medical Affairs, Boehringer Ingelheim, UK and Ireland. “We are committed to trying to improve the lives of people living with pulmonary fibrosis, particularly as these are rare diseases with a high level of unmet need.”
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, which is an irreversible scarring of lung tissue that negatively impacts lung function.4 Patients with ILD can develop a progressive fibrosing 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.5 The course of the disease and the symptoms are similar in progressive fibrosing ILDs regardless of the underlying disease.6
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 It demonstrated a consistent effect on lung function decline in patients with a UIP-like fibrotic pattern and those with other fibrotic patterns on high-resolution computed tomography (HRCT).1
The most common adverse event was diarrhoea (reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively), followed by nausea (28.9% nintedanib group vs. 9.4% placebo group) and vomiting (18.4% nintedanib group vs. 5.1% placebo).1 Elevations in alanine aminotransferase and aspartate aminotransferase were more common in patients treated with nintedanib than placebo.1 These were reversible on dose reduction, treatment interruption or discontinuation, or spontaneously.1 The safety profile observed in INBUILD® was consistent to what has been seen in IPF patients treated with nintedanib previously.1
1 Flaherty K, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases N Eng J Med. 29 September, 2019. NEJM.org. DOI: 10.1056/NEJMoa1908681.
2 European Medicines Agency. Ofev Summary of Product Characteristics. Available at: www.ema.europa.eu/en/documents/product-information/ofev-epar-product-information_en.pdf [Accessed September 2019].
3 Flaherty KR, et al. Characteristics of Patients with Progressive Fibrosing Interstitial Lung Diseases (ILDs) in the INBUILD Trial of Nintedanib. Abstract presented at American Thoracic Society International Conference. A5627 / 120. 2019, Dallas, US.
4 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].
5 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.
6 Kolb M, Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respiratory Research 2019:20:57.
7 Kim DS. Acute exacerbations in patients with idiopathic pulmonary fibrosis. Respiratory Research 2013;14(86). Available at: https://respiratory-research.biomedcentral.com/articles/10.1186/1465-9921-14-86 [Accessed September 2019].
8 Carone M et al. Obstructive lung function decline and IPF: The dark face of the moon. Chronic Respiratory Disease 2016;13(2):204–205.
9 Wijsenbeek M, et al. Non-IPF progressive fibrosing interstitial lung disease (PF-ILD): the patient journey. Am J Respir Crit Care Med 2018;197:A1678.
10 Flaherty KR, 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.
11 Ferrara G, et al. Best supportive care for idiopathic pulmonary fibrosis: current gaps and future directions. Eur Respir Rev. 2018;27:170076.