Nerandomilast is an orally administered, preferential phosphodiesterase 4B (PDE4B) inhibitor with antifibrotic and immunomodulatory effects.
It has been investigated in phase 3 clinical trials for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), where it demonstrated a statistically significant reduction in the decline of forced vital capacity (FVC) compared to placebo over 52 weeks, both as monotherapy and in combination with background antifibrotic therapy (nintedanib or pirfenidone).
Its most frequently reported adverse event is diarrhea, which is generally manageable and infrequently leads to treatment discontinuation.
Its mechanism of action involves inhibition of myofibroblast contractility and modulation of key fibrotic signaling pathways, including TGFβ and MAPK, as well as improvement of endothelial barrier function.