Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis

Frontiers in Pharmacology

Pharmacology

Fran Brown¹  Lu Zhang¹  Nelson Kinnersley²  Vis Niranjan³  Abhijeeth Chandrasekaran³  Pavithra Ramesh³  Ryan Adams⁴  Gennyne Walker⁴  Lauren Guy⁴ 

[1] Certara Inc., Princeton, NJ, United States;Octa Consulting Services Ltd., Harpenden, United Kingdom;RxMD, Chennai, India;aTyr Pharma, San Diego, CA, United States;

关键词: efzofitimod;    pulmonary sarcoidosis treatment;    exposure-response relationship;    steroid-sparing effect;    forced vital capacity;    King’s Sarcoidosis Questionnaire-Lung;   

DOI  :  10.3389/fphar.2023.1258236

 received in 2023-07-13, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.Conclusion: 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.Clinical Trial Registration: clinicaltrials.gov, identifier NCT03824392

【 授权许可】

Unknown   
Copyright © 2023 Walker, Adams, Guy, Chandrasekaran, Kinnersley, Ramesh, Zhang, Brown and Niranjan.