Boehringer Ingelheim, a leader in developing treatments for lung diseases, sponsored a phase 2 clinical trial investigating four doses of BIBF 1120 (nintedanib) in patients with idiopathic pulmonary fibrosis. The primary goal of “Safety and Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis” was to determine at least one superior dosing strategy compared to placebo that increased patients’ forced vital capacity (FVC).
Four treatment regimens, as well as one placebo, were considered in the trial. All patients were treated for a total of one year, but the dose and frequency of dosing were varied. Low dose (50 mg) BIBF 1120 once or twice daily, intermediate dose (100 mg) BIBF 1120 twice daily, or high dose (150 mg) BIBF 1120 twice daily were all tested in a total of 432 patients, ages 40 years and older. Patients were evenly split among the groups, with either 86 or 87 patients in each group, and subject withdrawals due to adverse events and other reasons were also spread fairly evenly.
Analysis of the results using mixed model analysis showed no significant difference among groups’ rate of decline in FVC, except in the case of placebo vs. high dose BIBF 1120. The treated group had a less negative change in rate of decline in FVC from baseline than did the placebo group (-0.060 vs. -0.190 liters per year).
While rate of decline in FVC was the primary outcome measure, a wide range of secondary measures were also used to evaluate the four doses of BIBF 1120. Similar to FVC, percent predicted FVC and absolute and relative changes from baseline in FVC were significantly better in the high dose BIBF 1120 group than in the placebo group, but this time intermediate dose was also superior to placebo. With 95% confidence statistics, the trial also identified higher survival (all causes of death and lung-transplant free) in patients treated with BIBF 1120.
These results were also published in The New England Journal of Medicine, under the title “Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis.”
In October 2014, the FDA approved nintedanib, with the marketed name of Ofev, to treat idiopathic pulmonary fibrosis. Ofev was on fast track, priority review status as an orphan product, which expedited its approval process to before the goal date for the product’s prescription drug user fee. As a kinase inhibitor, Ofev can block signaling pathways that lead to lung tissue scarring, enabling it to help patients’ FVC.
“[Ofev’s] approval expands the available treatment options for patients with idiopathic pulmonary fibrosis, a serious, chronic condition,” said Mary H. Parks, MD, deputy director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, in a news release from Boehringer Ingelheim. “Providing health care professionals and patients with additional treatment options helps enable appropriate care decisions based on a patient’s need.”