TrialLineage Concept
Antifibrotic therapy
Antifibrotic therapies are drugs designed to slow, halt, or reverse pathological fibrosis — the excessive scarring that impairs organ function. In pulmonary fibrosis, antifibrotic treatment aims to slow the decline in lung function by targeting the molecular mechanisms that drive fibroblast activation and matrix deposition.
What is antifibrotic therapy?
Until the 2010s, there were no approved therapies that directly targeted fibrosis. Patients with IPF were treated with corticosteroids and immunosuppressants, which were largely ineffective and sometimes harmful. The approval of pirfenidone (2014) and nintedanib (2014) marked the first generation of antifibrotic drugs — both demonstrated the ability to slow FVC decline in clinical trials.
These first-generation antifibrotics have broad mechanisms of action (pirfenidone modulates TGF-beta and inflammatory pathways; nintedanib inhibits multiple receptor tyrosine kinases). Neither stops progression entirely. The next generation of antifibrotic candidates — including LPA1 antagonists — targets more specific profibrotic pathways with the aim of additional or complementary efficacy.
Connection to the IPF lineage
BMS-986278 represents a next-generation antifibrotic approach — targeting a specific profibrotic signaling receptor (LPA1) rather than broad anti-inflammatory or multi-kinase mechanisms. The success of first-generation antifibrotics established both the clinical framework and the regulatory endpoint (FVC decline rate) that the BMS-986278 trial uses.