Nerandomilast and the Evolving Therapeutic Paradigm in Pulmonary Fibrosis: From Mechanism to Clinical Efficacy

ABSTRACT The recent Phase III FIBRONEER trials establish nerandomilast, a novel oral phosphodiesterase 4B (PDE4B) inhibitor, as an effective therapy for idiopathic and progressive pulmonary fibrosis. By elevating cyclic adenosine monophosphate (cAMP), it uniquely dual‐targets the NLRP3 inflammasome and TGF‐β pathway, addressing both inflammation and fibrosis. The trials demonstrated significant slowing of lung function decline, with a manageable safety profile. Critically, its efficacy on background antifibrotic therapy provides robust evidence for viable combination regimens, thereby ushering in a new era of combination therapy for this refractory disease. This marks a paradigm shift, offering renewed hope and paving the way for multi‐targeted treatment strategies, although longer‐term outcomes warrant further study.