Phase III INBUILD trial of Ofev meets endpoint in interstitial lung diseases.- Boehringer

Boehringer Ingelheim announced that in the Phase III INBUILD trial Ofev (nintedanib) slowed lung function decline by 57% across the overall study population, as assessed by the annual rate of decline in forced vital capacity (FVC) over 52 weeks in patients with fibrosing interstitial lung diseases (ILDs) with signs of progression. Just published in the New England Journal of Medicine and presented at the European Respiratory Society (ERS) Congress in Madrid, Spain, the study met its primary endpoint in patients with a broad range of fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF).

Nintedanib was shown to slow the rate of ILD progression independent of the fibrotic pattern seen on chest imaging. The side effect profile was consistent with previous studies of nintedanib in ILDs, with diarrhea being the most common adverse event. INBUILD is the first clinical trial in the field of ILDs to group patients based on the clinical behavior of their disease, rather than the primary clinical diagnosis.

In the INBUILD trial, nintedanib slowed lung function decline by 57% across the overall study population, with an adjusted annual rate of decline over 52 weeks in FVC of -80.8 mL/year compared to -187.8 mL/year for placebo (difference, 107.0 mL/year). The main secondary endpoints were the absolute change from baseline in King's Brief Interstitial Lung Disease (K-BILD) health status questionnaire total score at week 52, time to acute exacerbation of ILD or death over 52 weeks, and time to death over 52 weeks.

In the overall population, the change from baseline in health status at week 52 in the nintedanib and placebo groups, respectively, were 0.55 and -0.79. The proportion of patients with acute exacerbation of ILD or death over 52 weeks were 7.8% in the nintedanib group and 9.7% in the placebo group in the overall population. The proportion of patients who died over 52 weeks were 4.8% in the nintedanib group and 5.1% in the placebo group. An acute exacerbation is a sudden clinically significant deterioration in respiratory function, in many cases with unknown cause, which negatively impacts the disease course and often leads to death. The most common adverse event was diarrhea, reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively, with a safety profile consistent to what has been seen in nintedanib previously.

See: "Nintedanib in Progressive Fibrosing Interstitial Lung Diseases." Kevin R. Flaherty et al. NEJM September 29, 2019 DOI: 10.1056/NEJMoa1908681