Reduction in disease progression with nintedanib in the INPULSIS™ trials

Background: Nintedanib, an intracellular inhibitor of tyrosine kinases, is in development for the treatment of idiopathic pulmonary fibrosis (IPF). The INPULSIS™ trials were two replicate 52-week, randomized, double-blind, placebo-controlled Phase III trials that investigated the efficacy and safety of nintedanib 150 mg twice daily in 1066 patients with IPF. Declines in forced vital capacity (FVC) % predicted of > 5% and > 10% in patients with IPF have been proposed as indicators of disease progression and have been associated with reduced survival.

Aim: To determine the effect of nintedanib on changes in FVC % predicted in the INPULSIS™ trials.

Methods: The proportions of patients with absolute and relative declines in FVC % predicted of > 5% and > 10% at week 52 in each INPULSIS™ trial were determined in a post-hoc analysis.

Results: In each trial, a significantly greater proportion of patients in the placebo group had an absolute decline in FVC % predicted of > 5% compared with the nintedanib group. In INPULSIS™-1, a significantly greater proportion of patients in the placebo group had an absolute decline in FVC % predicted of > 10% compared with the nintedanib group; the difference between groups in INPULSIS™-2 was numerically in favour of nintedanib but did not reach statistical significance. In each trial, significantly greater proportions of patients in the placebo group had relative declines in FVC % predicted of > 5% and > 10% compared with the nintedanib group.

Conclusion: In the INPULSIS™ trials, nintedanib reduced the proportion of patients with IPF who experienced disease progression as measured by categorical FVC decline.

Presented at ERS 2014