Nintedanib, Boehringer Ingelheim’s treatment for patients with idiopathic pulmonary fibrosis (IPF), recently received positive opinions from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The findings from the Phase III INPULSIS® trials entitled “Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis” were published in the New England Journal of Medicine and showed that nintedanib, an intracellular inhibitor that targets various tyrosine kinases, reduced the forced vital capacity a parameter that correlates with a delay of disease progression in patients with idiopathic pulmonary fibrosis.
“Boehringer Ingelheim welcomes the decision by the CHMP. There has been a high unmet need for effective treatments that can slow disease progression in IPF. We look forward to making nintedanib available soon to patients with IPF in the EU,” said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim, in a press release.
Idiopathic Pulmonary Fibrosis (IPF) is a disease of the lung characterized by a progressive scarring of the lung tissue that leads to a decrease of functional lung volume and oxygen uptake. The origin of IPF is not known; many people live only for 3 to 5 years after diagnosis and the disease has no cure. The main cause of death of IPF is respiratory failure. The acute exacerbation of IPF (AE-IPF) has an extremely poor prognosis and is believed to occur per year in 5-10% of patients with IPF. In the United States and Europe, there are 200,000 patients with Idiopathic Pulmonary Fibrosis (IPF) including 48,000 new cases diagnosed every year (IPF Coalition, 2014).
“This decision is very encouraging as patients with IPF currently have very limited treatment options.” said INPULSIS® study investigator Professor Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease at the University of Southampton, United Kingdom. “For the first time we have a drug that has consistently met the primary endpoint in two large Phase III trials, confirming the results of the Phase II trial.”
The Phase III INPULSIS® trials were two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to assess the efficacy and safety of 150 mg of nintedanib given twice a day as compared with placebo in patients with idiopathic pulmonary fibrosis. There was one primary end point, the annual rate of decline in forced vital capacity (FVC), and two secondary end points, the time to the first acute exacerbation and the change from baseline in the total score on the St. George’s Respiratory Questionnaire. The last two parameters were evaluated after a 52-week period. These trials enrolled 1,066 patients from 24 countries. Nintedanib seems to affect growth factor receptors, like platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) that have been shown to be involved in the development of pulmonary fibrosis. Thus is likely that Nintedanib may reduce disease progression in IPF by decreasing the deterioration of lung function. The main results of these trials were that nintedanib decreased disease progression by reducing the annual rate of decline in lung function in a wide range IPF patients types by 50%, from patients with early disease to patients with emphysema. It also significantly reduced the probability of adjudicated acute exacerbations by 68%.
These findings are very important and have a high impact in the management and treatment of IPF, since around 50% of patients with acute IPF exacerbation die during hospitalization.