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Effect of Admilparant, a Lysophosphatidic Acid Receptor 1 Antagonist, on Disease Progression in Pulmonary Fibrosis

Year: 2025

Type: article

Abstract: BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are chronic fibrosing interstitial lung diseases associated with irreversible loss of lung function and early mortality. Admilparant (BMS-986278) is an oral lysophosphatidic acid receptor 1 antagonist under development for treatment of IPF and PPF. RESEARCH QUESTION: How does admilparant affect time to disease progression in patients with IPF or PPF? STUDY DESIGN AND METHODS: In a phase 2, randomized, double-anonymized, placebo-controlled study, parallel cohorts of patients with IPF or PPF were randomized separately 1:1:1 to receive 30 mg admilparant, 60 mg admilparant, or placebo twice daily for 26 weeks; background antifibrotics were allowed. The effect of admilparant vs placebo on time to disease progression was assessed post hoc. Disease progression was defined as a composite of relative decline of ≥ 10% in percent predicted FVC (ppFVC), acute exacerbation, all-cause hospitalization, and all-cause mortality. Subgroup analyses were performed based on median ppFVC at baseline. A Kaplan-Meier product-limit approach assessed time to first event of disease progression over 26 weeks. RESULTS: In total, 255 patients with IPF and 114 patients with PPF were included. Median ppFVC at baseline was 77.3% and 64.7% in the IPF and PPF cohorts, respectively. Treatment with 60 mg admilparant delayed time to disease progression over 26 weeks compared with placebo in both cohorts of patients (IPF: hazard ratio, 0.54; 95% CI, 0.31-0.95; PPF: hazard ratio, 0.41; 95% CI, 0.18-0.90). A similar trend was observed in the subgroup analysis of patients with ppFVC at baseline either below or above the median value. In both cohorts, the most frequent first event was relative decline of ≥ 10% in ppFVC; no deaths were reported as first progression events. INTERPRETATION: These findings support further evaluation of admilparant as a therapeutic option for patients with IPF or PPF in phase 3 trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04308681; URL: www. CLINICALTRIALS: gov.

Source: CHEST Journal

DOI: 10.1016/j.chest.2025.04.003