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=14

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=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusion:</bold> 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.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">clinicaltrials.gov</ext-link>, identifier NCT03824392</p>