Effects of lysophosphatidic acid receptor 1 (LPA1) antagonism on biomarkers in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): data from a randomized phase 2 trial with BMS-986278

<bold>Introduction:</bold> BMS-986278, an oral LPA₁ antagonist, reduced lung function decline over 26 weeks in a phase 2 trial with IPF and PPF cohorts (<ext-link>NCT04308681</ext-link>). <bold>Aims & Objectives:</bold> To assess changes in biomarkers following treatment with BMS-986278. <bold>Methods:</bold> Patients with IPF (n=278) or PPF (n=125) were randomized 1:1:1 to receive BMS-986278 (30 or 60 mg) or placebo (PBO) twice daily for 26 weeks; background antifibrotics were allowed. Changes from baseline in biomarkers involved in epithelial injury, inflammation, and fibrosis were analyzed with a linear mixed effects model for the 30 and 60 mg BMS-986278 groups vs PBO separately in the IPF and PPF cohorts. <bold>Results:</bold> In the IPF cohort, significant biomarker changes relative to PBO were observed at week 26 in patients treated with 60 mg BMS-986278 including increased adiponectin levels (<italic>P</italic><0.0001) and decreased markers of epithelial injury and fibrosis (CA-125, matrix metalloproteinase-7, tenascin C, PRO-FIB; <italic>P</italic><0.05). In the PPF cohort, 60 mg BMS-986278 significantly decreased the TGF-β pathway marker, periostin, and multiple inflammatory markers including YKL-40, VCAM-1, and ferritin (<italic>P</italic><0.05), relative to PBO at week 26. <bold>Conclusions:</bold> Treatment with BMS-986278 over 26 weeks significantly improved biomarkers of epithelial injury and fibrosis in patients with IPF, and biomarkers of inflammation and fibrosis in patients with PPF, consistent with effective antagonism of the LPA₁ pathway.