• Tamera J Corte, Juergen Behr, Vincent Cottin, Marilyn K Glassberg, Michael Kreuter, Fernando J Martinez, Takashi Ogura, Takafumi Suda, Marlies Wijsenbeek, Elchonon Berkowitz, Brandon Elpers, Sinae Kim, Hideaki Watanabe, Aryeh Fischer, and Toby M Maher.
• Royal Prince Alfred Hospital, Department of Respiratory Medicine, Sydney, New South Wales, Australia.
• Am. J. Respir. Crit. Care Med. 2024 Oct 11.

RationaleIdiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed.ObjectivesAssess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF.MethodsThis 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 admilparant, 60-mg admilparant, or placebo (1:1:1) twice daily for 26 weeks. Background antifibrotics (both cohorts) and immunosuppressants (PPF only) were permitted.Measurements And Main ResultsRates of change in percentage of predicted forced vital capacity (ppFVC) 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% CI, -0.1 to 3.0) for IPF and 3.2% (95% CI, 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 post-dose blood pressure reductions were observed in all arms in both cohorts but greater with admilparant. Treatment discontinuations due to adverse events were similar across IPF arms and lower with admilparant (2.5% [30-mg]; 0% [60-mg]) versus placebo (17.1%) for PPF.ConclusionsIn 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. Clinical trial registration available at www.Clinicaltrialsgov, ID: NCT04308681.

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