Trials of Nintedanib in Idiopathic Pulmonary Fibrosis (INPULSIS-1 and INPULSIS-2)

Nintedanib is a tyrosine kinase inhibitor that blocks multiple growth factor receptors involved in fibrosis (PDGFR, FGFR, VEGFR). The TOMORROW phase 2 trial showed promising results, leading to these two parallel phase 3 trials.

Two parallel multicenter RCTs (INPULSIS-1: n=515; INPULSIS-2: n=552) comparing nintedanib 150 mg twice daily vs. placebo in patients with IPF over 52 weeks.

In both trials, nintedanib significantly reduced the annual rate of FVC decline (INPULSIS-1: −114.7 vs −239.9 ml/year, p<0.001; INPULSIS-2: −113.6 vs −207.3 ml/year, p<0.001). INPULSIS-2 also showed a significant reduction in acute exacerbations.

Nintedanib significantly slows FVC decline in IPF and is FDA-approved. Along with pirfenidone, it is standard of care. Main side effect is diarrhea (occurs in ~60% but manageable with dose reduction).

FVC decline is a surrogate endpoint — mortality benefit was not demonstrated in individual trials. Diarrhea is a major tolerability issue.