During the European Respiratory Society International Congress (ERS) 2014, held in Munich, Germany last month, a pre-specified subgroup analysis from the two replicate Phase III INPULSIS™ trials revealed that treatment with nintedanib retarded the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). The study’s findings were independent of severity of lung function deterioration before treatment, with a reduction in disease progression in IPF patients measured by the decline on categorical forced vital capacity (FVC).
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. Nintedanib is an experimental tyrosine kinase inhibitor (TKI) developed by Boehringer Ingelheim for idiopathic pulmonary fibrosis, but its safety and efficacy have not been fully established until now.
The mode of action of this drug is through targeting growth factor receptors, mainly the platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR), which have been shown to contribute to the pathogenesis of pulmonary fibrosis. Since this drug inhibits biological processes that contribute to fibrosis, it has the potential to reduce disease progression in IPF by decreasing the deterioration of lung function. In addition, nintedanib is currently in clinical development as a therapy for cancer, including non-small cell lung cancer, ovarian cancer, colorectal cancer and hepatocellular carcinoma.
The INPULSIS™ trials, INPULSIS-1 and INPULSIS-2, were two replicate randomized, double-blind, placebo-controlled, 52-week Phase III trials that assessed the efficacy and safety of nintedanib 150 mg twice a day in 1,066 patients who were at least 40 years of age, diagnosed with IPF within five years before the trials, and based on the American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and Latin American Thoracic Association (ALAT) guidelines for diagnosis and management of IPF across 24 countries. The analysis of INPULSIS™ data addressed the decline in lung function in two pre-specified groups per year — baseline forced vital capacity (FVC) of >70% (n=700) and ≤70% predicted (n=361).
The data, which was presented by Professor Costabel, from Ruhrlandklinik University Hospital, Germany and Dr. Cottin, from Centre national de référence des maladies pulmonaires rares, université Claude-Bernard Lyon, France, showed that the nintedanib regimen, 150 mg twice a day, slowed the decline in lung function in patients with IPF, independent of severity of lung function impairment before treatment. A decline in FVC % predicted that >5% and >10% over 6 or 12 months in patients with IPF is a biomarker of disease progression and is associated with reduced survival. In each trial, the placebo group had a significantly higher probability of relative declines in FVC % predicted of >5% and >10%, increased disease progression, than the nintedanib-treated group, i.e. slower disease progression. Therefore, the main conclusion was that in the INPULSIS™ trials, nintedanib reduced the relative amount of patients with IPF and retarded disease progression measured by categorical FVC decline, independently of severity of lung .
“Nintedanib is the first targeted treatment for IPF to consistently meet the primary endpoint in two identically designed Phase III trials and this sub-analysis further underscores its efficacy in IPF patients presenting different ranges of lung function impairment at baseline,” said Professor Ulrich Costabel, in Boehringer Ingelheim press release.
“The results of these analyses further confirm and support the efficacy of nintedanib* on slowing disease progression in a wide range of patients with IPF,” said Dr Susanne Stowasser, Global Team Leader Medical Affairs, Boehringer Ingelheim. “Boehringer Ingelheim is committed to studying nintedanib* further and to making it available to patients with IPF and their treating physicians as soon as possible,” added Dr. Stowasser in the Boehringer press release.