Advances in the Treatment of Idiopathic Pulmonary Fibrosis: New Drugs and Therapies

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology, characterized by irreversible fibrotic remodeling of the lung parenchyma, ultimately leading to respiratory failure. Despite advances with antifibrotic agents such as nintedanib and pirfenidone, the median survival of patients remains poor, highlighting the urgent need for innovative therapies capable of altering the disease trajectory. In recent years, the development of drugs targeting specific pathogenic pathways – including lysophosphatidic acid receptor 1 (LPA1), integrins, autotaxin, connective tissue growth factor (CTGF), pentraxin-2, PDE4B and TNIK – has become the cornerstone of translational and clinical research.

This integrative review examines the most recent evidence (2023–2025) regarding emerging therapeutic agents for IPF, focusing on phase II and III clinical trials with promising molecules. Among them, admilparant (LPA1 antagonist), bexotegrast (integrin inhibitor), ziritaxestat (autotaxin inhibitor), pamrevlumab (anti-CTGF antibody), zinpentraxin alfa (PRM-151, immunomodulator), nerandomilast (PDE4B inhibitor), and rentosertib (TNIK inhibitor identified through artificial intelligence) stand out. These agents have demonstrated reductions in forced vital capacity (FVC) decline, improvements in serum biomarkers, and positive impacts on functional outcomes, although the safety profile of some requires careful monitoring.

In conclusion, IPF therapy is expanding, with multiple molecular targets being evaluated in robust clinical trials. While long-term outcomes are still awaited, these emerging drugs provide concrete perspectives for extending survival and improving quality of life in patients with IPF.