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SAN DIEGO – Compared with placebo, the investigative tyrosine kinase inhibitor nintedanib helped preserve forced vital capacity in patients with idiopathic pulmonary fibrosis, according to phase III results presented at an international conference of the American Thoracic Society.
Across two trials, 1,066 patients were randomized 3:2 to 150 mg of nintedanib twice daily or placebo for 52 weeks. In INPULSIS-1, the adjusted annual rate of change in forced vital capacity (FVC) was –114.7 mL with nintedanib versus –239.9 mL with placebo (difference 125.3 mL; 95% confidence interval, 77.7-172.8; P less than .001). In INPULSIS-2, the rate of change was –113.6 mL with nintedanib versus –207.3 mL with placebo (difference 93.7 mL; 95% CI, 44.8 to 142.7; P less than .001).
"The curves for changes from baseline in FVC over time in the nintedanib and placebo groups separated early in the two studies and continued to diverge over time," the researchers wrote (N. Engl. J. Med. 2014 May 18 [doi:10.1056/NEJMoa1402584]). MIs were reported in five (1.6%) nintedanib patients and one (0.5%) placebo patient in the first trial and five (1.5%) nintedanib patients and one (0.5%) placebo patient in the second. Two MIs in the nintedanib groups and one in the placebo groups were fatal.
Idiopathic pulmonary fibrosis (IPF) is a serious disease "for which there are currently no FDA-approved treatments. We are all very excited by these data because they suggest evidence of nintedanib’s impact on lung function loss in patients with IPF. Overall, [it’s] a positive message that we are making progress," said lead investigator Dr. Luca Richeldi, chair of interstitial lung disease at the University of Southampton (England).
Results were mixed on secondary endpoints. There was no significant between-group difference in death from any cause or respiratory causes; 5.5% of nintedanib patients and 7.8% of placebo patients died. Likewise, the time to first acute exacerbation and progression on the St. George’s Respiratory Questionnaire (SGRQ) were significantly delayed only in INPULSIS-2, not INPULSIS-1. On pooled analysis, nintedanib offered no advantage over placebo in time to first exacerbation (hazard ratio, 0.64; 95% CI, 0.39-1.05; P = .08) or mean 52-week change from baseline SGRO.
The "difference in the key secondary endpoint between [the trials] was not explained by the differences in baseline characteristics." Exacerbations "are relatively rare events in patients with [IPF] who are in clinical trials and are difficult to assess and categorize, which may explain some of the heterogeneity in our findings," the researchers said.
About 62% of nintedanib patients versus 18% of placebo patients reported diarrhea. Liver enzyme levels three times above normal were found in 5% of nintedanib patients and less than 1% of placebo patients.
Eighty percent of the subjects were men. Average age was 67 years. Baseline FVC was 80% of predicted value in all study arms.
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SAN DIEGO – Compared with placebo, the investigative tyrosine kinase inhibitor nintedanib helped preserve forced vital capacity in patients with idiopathic pulmonary fibrosis, according to phase III results presented at an international conference of the American Thoracic Society.
Across two trials, 1,066 patients were randomized 3:2 to 150 mg of nintedanib twice daily or placebo for 52 weeks. In INPULSIS-1, the adjusted annual rate of change in forced vital capacity (FVC) was –114.7 mL with nintedanib versus –239.9 mL with placebo (difference 125.3 mL; 95% confidence interval, 77.7-172.8; P less than .001). In INPULSIS-2, the rate of change was –113.6 mL with nintedanib versus –207.3 mL with placebo (difference 93.7 mL; 95% CI, 44.8 to 142.7; P less than .001).
"The curves for changes from baseline in FVC over time in the nintedanib and placebo groups separated early in the two studies and continued to diverge over time," the researchers wrote (N. Engl. J. Med. 2014 May 18 [doi:10.1056/NEJMoa1402584]). MIs were reported in five (1.6%) nintedanib patients and one (0.5%) placebo patient in the first trial and five (1.5%) nintedanib patients and one (0.5%) placebo patient in the second. Two MIs in the nintedanib groups and one in the placebo groups were fatal.
Idiopathic pulmonary fibrosis (IPF) is a serious disease "for which there are currently no FDA-approved treatments. We are all very excited by these data because they suggest evidence of nintedanib’s impact on lung function loss in patients with IPF. Overall, [it’s] a positive message that we are making progress," said lead investigator Dr. Luca Richeldi, chair of interstitial lung disease at the University of Southampton (England).
Results were mixed on secondary endpoints. There was no significant between-group difference in death from any cause or respiratory causes; 5.5% of nintedanib patients and 7.8% of placebo patients died. Likewise, the time to first acute exacerbation and progression on the St. George’s Respiratory Questionnaire (SGRQ) were significantly delayed only in INPULSIS-2, not INPULSIS-1. On pooled analysis, nintedanib offered no advantage over placebo in time to first exacerbation (hazard ratio, 0.64; 95% CI, 0.39-1.05; P = .08) or mean 52-week change from baseline SGRO.
The "difference in the key secondary endpoint between [the trials] was not explained by the differences in baseline characteristics." Exacerbations "are relatively rare events in patients with [IPF] who are in clinical trials and are difficult to assess and categorize, which may explain some of the heterogeneity in our findings," the researchers said.
About 62% of nintedanib patients versus 18% of placebo patients reported diarrhea. Liver enzyme levels three times above normal were found in 5% of nintedanib patients and less than 1% of placebo patients.
Eighty percent of the subjects were men. Average age was 67 years. Baseline FVC was 80% of predicted value in all study arms.
SAN DIEGO – Compared with placebo, the investigative tyrosine kinase inhibitor nintedanib helped preserve forced vital capacity in patients with idiopathic pulmonary fibrosis, according to phase III results presented at an international conference of the American Thoracic Society.
Across two trials, 1,066 patients were randomized 3:2 to 150 mg of nintedanib twice daily or placebo for 52 weeks. In INPULSIS-1, the adjusted annual rate of change in forced vital capacity (FVC) was –114.7 mL with nintedanib versus –239.9 mL with placebo (difference 125.3 mL; 95% confidence interval, 77.7-172.8; P less than .001). In INPULSIS-2, the rate of change was –113.6 mL with nintedanib versus –207.3 mL with placebo (difference 93.7 mL; 95% CI, 44.8 to 142.7; P less than .001).
"The curves for changes from baseline in FVC over time in the nintedanib and placebo groups separated early in the two studies and continued to diverge over time," the researchers wrote (N. Engl. J. Med. 2014 May 18 [doi:10.1056/NEJMoa1402584]). MIs were reported in five (1.6%) nintedanib patients and one (0.5%) placebo patient in the first trial and five (1.5%) nintedanib patients and one (0.5%) placebo patient in the second. Two MIs in the nintedanib groups and one in the placebo groups were fatal.
Idiopathic pulmonary fibrosis (IPF) is a serious disease "for which there are currently no FDA-approved treatments. We are all very excited by these data because they suggest evidence of nintedanib’s impact on lung function loss in patients with IPF. Overall, [it’s] a positive message that we are making progress," said lead investigator Dr. Luca Richeldi, chair of interstitial lung disease at the University of Southampton (England).
Results were mixed on secondary endpoints. There was no significant between-group difference in death from any cause or respiratory causes; 5.5% of nintedanib patients and 7.8% of placebo patients died. Likewise, the time to first acute exacerbation and progression on the St. George’s Respiratory Questionnaire (SGRQ) were significantly delayed only in INPULSIS-2, not INPULSIS-1. On pooled analysis, nintedanib offered no advantage over placebo in time to first exacerbation (hazard ratio, 0.64; 95% CI, 0.39-1.05; P = .08) or mean 52-week change from baseline SGRO.
The "difference in the key secondary endpoint between [the trials] was not explained by the differences in baseline characteristics." Exacerbations "are relatively rare events in patients with [IPF] who are in clinical trials and are difficult to assess and categorize, which may explain some of the heterogeneity in our findings," the researchers said.
About 62% of nintedanib patients versus 18% of placebo patients reported diarrhea. Liver enzyme levels three times above normal were found in 5% of nintedanib patients and less than 1% of placebo patients.
Eighty percent of the subjects were men. Average age was 67 years. Baseline FVC was 80% of predicted value in all study arms.
Major finding: In the first trial, the adjusted annual rate of change in FVC was –114.7 mL with nintedanib versus –239.9 mL with placebo. In the second, the rate of change was –113.6 mL with nintedanib versus –207.3 mL with placebo.
Data source: Randomized, controlled trials involving patients with IPF.
Disclosures: Boehringer Ingelheim and the British National Health Service funded the work. Dr. Richeldi disclosed ties with InterMune, MedImmune, Roche, Takeda, Biogen Idec, Sanofi Aventis, ImmuneWorks, and Shionogi. Some coauthors disclosed ties with Boehringer Ingelheim, maker of nintedanib.
