Nintedanib was granted Orphan Drug Designation in the EU for the treatment of idiopathic pulmonary fibrosis (IPF) in May 2013. It has not yet been filed for approval in the EU or the US.
An accompanying editorial discusses the results of this study, and another evaluating pirfenidone in the treatment of IPF. This notes that there has been little in the way of treatment to offer patients with IPF, a chronic, progressive disorder of lung scarring that has a 3-year survival of 50%.
The two placebo-controlled INPULSIS Phase III trials evaluating nintedanib were conducted simultaneously. The magnitude of the effect of nintedanib on preventing acute exacerbations varied between the two trials, and there was no evidence of improvement in scores for respiratory symptoms. Although these trials were not powered to detect statistically significant differences in mortality, there was a trend toward a reduced rate of death that mirrored the reduced rate of decline in lung function.
The ASCEND trial evaluating pirfenidone was the fourth in a series of placebo-controlled Phase III trials. The results of the first three trials were mixed; leading to its approval by many governing bodies, but not by the US FDA. In the current study pirfenidone reduced the one-year rate of forced vital capacity (FVC) decline; it was also associated with a reduced decline in distances on the 6-minute walk test, but no effect on respiratory symptoms were noted. An analysis combining the 1-year results of this study with the previously reported CAPACITY studies suggested a possible mortality benefit.
The differences in the overall rate of decline in FVC between the INPULSIS and ASCEND studies may be explained by differences in recruitment criteria, which resulted in the average patient with IPF in the INPULSIS trials having less severe disease than the average patient in the ASCEND trial.
Despite the positive findings, which the authors of the editorial say are a major breakthrough for patients with this disease; caution should be taken when extrapolating the results to patients who fall outside the inclusion criteria. It is not known if these drugs will have a beneficial effect in patients with more severe disease or with an acute exacerbation, and the durability of the results beyond one year remains to be determined.