Pneumologie 2015; 69 - P235
DOI: 10.1055/s-0035-1544829

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis: Results of two 52-week, Phase III, randomized, placebo-controlled trials (INPULSIS™)

U Costabel 1, L Richeldi 2, RM du Bois 3, G Raghu 4, A Azuma 5, KK Brown 6, V Cottin 7, KR Flaherty 8, Y Inoue 9, DS Kim 10, M Kolb 11, PW Noble 12, M Selman 13, H Taniguchi 14, M Brun 15, M Girard 15, R Schlenker-Herceg 16, B Disse 17, HR Collard 18
  • 1Ruhrlandklinik, Abteilung für Pneumologie, Allergologie, Universität Duisburg-Essen
  • 2National Institute for Health Research Southampton Respiratory Biomedical Research Unit and University of Southampton
  • 3Imperial College London
  • 4University of Washington
  • 5Nippon Medical School Tokyo
  • 6National Jewish Health, Denver
  • 7Louis Pradel Hospital, University of Lyon
  • 8University of Michigan Health System, Ann Arbor
  • 9National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka
  • 10Asan Medical Center, University of Ulsan, Seoul
  • 11McMaster University Hamilton
  • 12Cedars-Sinai Medical Center Los Angeles
  • 13Instituto Nacional de Enfermedades Respiratorias, México City
  • 14Tosei General Hospital Aichi
  • 15Boehringer Ingelheim France S.A.S., Reims
  • 16Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield
  • 17Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim am Rhein
  • 18University of California San Francisco

Background: Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases.

Methods: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 [NCT01335464] and INPULSIS-2 [NCT01335477]) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis (IPF). The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George's Respiratory Questionnaire, both assessed over a 52-week period.

Results: A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was –114.7 ml with nintedanib versus –239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; p < 0.001) in INPULSIS-1 and –113.6 ml with nintedanib versus –207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; p < 0.001) in INPULSIS-2. In INPULSIS-2, there was a significant benefit with nintedanib in the time to the first acute exacerbation versus placebo (hazard ratio (HR), 0.38; 95% CI, 0.19 to 0.77; P= 0.005); in INPULSIS-1, no significant difference was found (HR, 1.15; 95% CI, 0.54 to 2.42; P= 0.67); The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% (nintedanib vs. placebo) in INPULSIS-1 as well as 63.2% and 18.3% in INPULSIS-2, respectively.

Conclusions: In patients with IPF, nintedanib significantly reduced the decline in FVC by approximately 50%, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients.

Presented at ATS 2014