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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. Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).

Background: Real-world data on the use, healthcare resource utilization (HCRU), and associated costs of antifibrotic therapies in patients with idiopathic pulmonary fibrosis (IPF) are limited., Objectives: To assess the prevalence of antifibrotic treatment, characteristics of patients receiving treatment, discontinuation rates, and HCRU and costs associated with treatment., Design: This retrospective study analyzed de-identified longitudinal and cross-sectional data, respectively, from two US claims databases: Optum's de-identified Clinformatics ® Data Mart Database (CDM; commercial claims, Medicare Advantage) and the Veterans Health Administration (VHA) database. The study periods were October 1, 2013-March 31, 2019 and October 1, 2014-September 30, 2019, respectively. Eligible individuals were adults with ⩾1 diagnosis claim for IPF., Methods: Antifibrotic prevalence, patient demographics, treatment discontinuation rates, and HCRU and costs were determined separately for each cohort and described using summary statistics. Bivariate comparisons were analyzed using Chi-square and Student's t -tests for categorical and continuous variables, respectively., Results: Overall, 4223 and 4459 eligible patients were identified in the CDM and VHA databases, respectively. Prevalence of antifibrotic uptake was 9.2% and 29.1% and the rate of index treatment discontinuation was 47% and 66% during follow-up in the CDM and VHA cohorts, respectively. Antifibrotic-treated patients were significantly younger ( p  < 0.0001) with lower mean Charlson Comorbidity Index scores at baseline versus untreated patients in both cohorts. In the CDM cohort, the number of outpatient and pharmacy visits was significantly higher in treated versus untreated patients during follow-up (both p  < 0.0001). A similar trend was observed for the VHA cohort. Total follow-up costs in both cohorts were significantly higher in treated versus untreated patients due to higher pharmacy costs (CDM; p  < 0.0001) or higher outpatient and pharmacy costs (VHA; p  < 0.0001)., Conclusion: The low prevalence of antifibrotic usage in both cohorts, together with the high rate of antifibrotic discontinuation, and increased HCRU and costs in treated versus untreated patients, support the need for novel treatment options for IPF., Trial Registration: Not applicable.

Introduction: Idiopathic pulmonary fibrosis (IPF) and non-IPF, progressive fibrotic interstitial lung diseases (PF-ILD), are associated with a progressive loss of lung function and a poor prognosis. Treatment with antifibrotic agents can slow, but not halt, disease progression, and treatment discontinuation because of adverse events is common. Fibrotic diseases such as these can be mediated by lysophosphatidic acid (LPA), which signals via six LPA receptors (LPA 1-6 ). Signalling via LPA 1 appears to be fundamental in the pathogenesis of fibrotic diseases. BMS-986278, a second-generation LPA 1 antagonist, is currently in phase 2 development as a therapy for IPF and PF-ILD., Methods and Analysis: This phase 2, randomised, double-blind, placebo-controlled, parallel-group, international trial will include adults with IPF or PF-ILD. The trial will consist of a 42-day screening period, a 26-week placebo-controlled treatment period, an optional 26-week active-treatment extension period, and a 28-day post-treatment follow-up. Patients in both the IPF (n=240) and PF-ILD (n=120) cohorts will be randomised 1:1:1 to receive 30 mg or 60 mg BMS-986278, or placebo, administered orally two times per day for 26 weeks in the placebo-controlled treatment period. The primary endpoint is rate of change in per cent predicted forced vital capacity from baseline to week 26 in the IPF cohort., Ethics and Dissemination: This study will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication., Trial Registration Number: NCT04308681., Competing Interests: Competing interests: TJC has served on advisory boards for Boehringer Ingelheim, Hoffman-LaRoche, Bristol Myers Squibb, Ad-Alta, Promedior and Prometic Life Sciences. Her institution has received grants or research fees from Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Galápagos and Hoffman-La Roche, outside the submitted work. LL has served on advisory boards for United Therapeutics, Bristol Myers Squibb, AstraZeneca, Galápagos, Genentech and DevPro Biopharma; and has received research funding from Biogen, Celgene, Novartis, Bellerophon Therapeutics, Galecto, Bristol Myers Squibb, Respivant Sciences, Galápagos, Boehringer Ingelheim, Roche and Pliant Therapeutics; and has provided disease-state education for Genentech, Boehringer Ingelheim, United Therapeutics and Veracyte. JJS receives honoraria from Genentech for giving unbranded, disease-state talks on IPF; he also receives grant support from Genentech and Boehringer Ingelheim. He is a paid consultant for Boehringer Ingelheim and an unpaid consultant for Bristol Myers Squibb. TMM has received personal fees from AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galápagos, GlaxoSmithKline, Indalo Therapeutics, Pliant Therapeutics, Roche, and UCB, outside the submitted work. His institution received grants or research fees from AstraZeneca, GlaxoSmithKline and UCB outside the submitted work. JGG is the founder of MedQIA, LLC. SMP has consulted or served on advisory boards for Boehringer Ingelheim, Bristol Myers Squibb and Altavant; and has received research funding to Duke from Boehringer Ingelheim, Bristol Myers Squibb and AstraZeneca. TS has served on advisory boards for Bristol Myers Squibb and has received an honorarium and research funding from Boehringer Ingelheim. TO has served on advisory boards for Bristol Myers Squibb and has received personal fees from Boehringer Ingelheim, Shionogi, Astellas Pharma and Toray industries. AM is a consultant for Bristol Myers Squibb. XZ, GST, BE, HX, HW, RAS, EDC and AF are all employees of Bristol Myers Squibb., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)