AUTHOR=Walker Gennyne , Adams Ryan , Guy Lauren , Chandrasekaran Abhijeeth , Kinnersley Nelson , Ramesh Pavithra , Zhang Lu , Brown Fran , Niranjan Vis TITLE=Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis JOURNAL=Frontiers in Pharmacology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1258236 DOI=10.3389/fphar.2023.1258236 ISSN=1663-9812 ABSTRACT=Background: Preliminary evidence for efficacy in pulmonary sarcoidosis has been shown for efzofitimod. Here we present supportive evidence of efficacy based on an exposure-response analysis. Methods: Data from two studies (Phase 1, N=24, single dose in healthy volunteers, and Phase 1b/2a, N=25, multiple doses over 24 weeks in participants with pulmonary sarcoidosis) were used to build a population pharmacokinetic model. Using this model, the relationship between efzofitimod exposure and three prespecified efficacy parameters (mean daily oral corticosteroid [OCS] dose, percent-predicted forced vital capacity [ppFVC] and King's Sarcoidosis Questionnaire-Lung [KSQ-Lung] score) was explored. Linear regression described the relationship of efzofitimod exposure and OCS reduction, ppFVC and KSQ-Lung score. Logistic regression related efzofitimod exposure to the probability of achieving a minimal clinically important difference for ppFVC and KSQ-Lung score. Due to the small study size, trends (not statistical significance) in relationships are reported. Results: In patients with pulmonary sarcoidosis, as efzofitimod exposure increased, the mean daily OCS dose decreased, and ppFVC and KSQ-Lung score improved over baseline. The slope for all the endpoints by both linear and logistic regression showed an improving trend with increased exposure. Conclusions: These preliminary findings of a positive exposure-response across multiple efficacy endpoints support the claim that proof of concept has been established for the use of efzofitimod in pulmonary sarcoidosis. Trial registration: ClinicalTrials.gov NCT03824392 dated 31/01/2019.