INSTAGE trial data on Ofev in IPF published in NEJM.- Boehringer.

Results from the INSTAGE trial of Ofev (nintedanib), from Boehringer, in people with idiopathic pulmonary fibrosis (IPF), have been presented at the 2018 European Respiratory Society (ERS) conference in Paris and published in the New England Journal of Medicine. The trial reports clinical data on a subset of patients with IPF and severe impairment in gas exchange, for whom only limited data exist. Data suggest that the efficacy and safety profiles of nintedanib in INSTAGE were consistent with the profiles observed in patients with less advanced disease in the INPULSIS and TOMORROW trials.

INSTAGE was conducted to investigate the efficacy and safety of nintedanib plus sildenafil vs. nintedanib monotherapy in patients with IPF and severely impaired gas exchange (DLco of less or equal to 35% predicted), who have largely been excluded from previous trials. Therefore INSTAGE provides important clinical insights on this cohort. INSTAGE was a randomised, double-blind, parallel-group trial with a total enrollment of 274 patients. The trial concluded that the addition of sildenafil on top of nintedanib did not provide significant improvement in change from baseline in SGRQ total score at week 12 (primary endpoint) compared to nintedanib therapy alone. In the INSTAGE trial, the change in FVC from baseline to 12 and 24 weeks in patients treated with nintedanib alone was -25.5 and -58.2 mL, respectively. This compares very well with the changes in FVC observed in the Phase III INPULSIS trials.

Although the study did not reach statistical significance in regards to the primary endpoint and the findings described above are considered exploratory, they provide clinically relevant new information. No new safety signals were identified. The proportions of patients who reduced or interrupted nintedanib to manage adverse events, or who discontinued nintedanib prematurely due to adverse events, were similar to those in the INPULSIS trials. Diarrhoea was the most frequent adverse event.

Comment: The INSTAGE data are important because in patients with severely impaired gas exchange, we previously only had limited data on the efficacy and safety of IPF treatments, including nintedanib. These results seem to support the use of nintedanib across a range of IPF patients.

See: "Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis" Martin Kolb et al. NEJM September 15, 2018 DOI: 10.1056/NEJMoa1811737