Efficacy and Safety of Admilparant, an LPA1 Antagonist, in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial

Abstract Rationale Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Objectives Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. Methods This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted. Measurements and Main Results Rates of change in percentage of predicted FVC over 26 weeks for IPF were −2.7% (placebo), −2.8% (30 mg), and −1.2% (60 mg) and for PPF were −4.3% (placebo), −2.9% (30 mg), and −1.1% (60 mg). Treatment differences between 60-mg admilparant and placebo were 1.4% (95% confidence interval, −0.1 to 3.0) for IPF and 3.2% (95% confidence interval, 0.7 to 5.7) for PPF. Treatment effect was observed with or without background antifibrotics in both cohorts. Diarrhea occurred at similar frequencies in admilparant arms versus placebo. Transient Day 1 postdose blood pressure reductions were observed in all arms in both cohorts but were greater with admilparant. Treatment discontinuations because of adverse events were similar across IPF arms and lower with admilparant (2.5% [30 mg]; 0% [60 mg]) versus placebo (17.1%) for PPF. Conclusions In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials.