[Comparative analysis of drug therapy for fibrotic interstitial lung diseases based on results of phase 3 trials]

Idiopathic pulmonary fibrosis (IPF) and other progressive pulmonary fibrosis (PPF) forms are associated with significant morbidity and mortality. Pirfenidone and nintedanib are the currently approved antifibrotic drugs in Germany. Based on the positive results of both Phase-3 trials FIBRONEER-IPF and FIBRONEER-ILD, the phosphodiesterase-4B inhibitor nerandomilast was approved in 2025 for the treatment of IPF in USA, but not yet in Germany.

We performed a comparative analysis of the results of phase 3 randomized clinical trials of pirfenidone, nintedanib and nerandomilast regarding patient characteristics, efficacy and safety.

Eight phase 3 trials were included: 3 with pirfenidone, 3 with nintedanib, und 2 with nerandomilast. The characteristics of the trials' populations showed substantial differences. In terms of the primary endpoint reduction of FVC decline over one year, all the three compounds demonstrated similar efficacy. Secondary endpoints across the trials were heterogeneous, and no positive efficacy for patient-reported outcomes was observed for any of the three drugs. The best tolerability and safety profile was demonstrated for nerandomilast.

In the near future, nerandomilast could become the third available antifibrotic drug in Germany for the treatment of IPF and PPF, showing a similar efficacy profile to pirfenidone and nintedanib, with a better tolerability. The different trials populations should be considered when comparing the clinical trials results. New guidelines are mandatory to unravel the role of nerandomilast in the treatment algorithm of IPF and PPF.