Conference Coverage
Vital capacity preserved in IPF with investigational agent nintedanib
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.
DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.
Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).
“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).
Dr. Luca Richeldi
Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).
Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).
A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).
“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”
One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”
The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.
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