Ingelheim, Germany, 30th September 2019 – 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) over 52 weeks in patients with fibrosing interstitial lung disease (ILDs) with signs of progression. 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. 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. The course of the disease and the symptoms are similar in progressive fibrosing ILDs regardless of the underlying disease.
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 effect 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.”
 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