Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis
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, m...
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Frontiers Media S.A.,
2023-10-01T00:00:00Z.
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|---|---|---|---|
| 001 | doaj_3f7393ecf74b4edbbe2b6fa84a82a5d3 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Gennyne Walker |e author |
| 700 | 1 | 0 | |a Ryan Adams |e author |
| 700 | 1 | 0 | |a Lauren Guy |e author |
| 700 | 1 | 0 | |a Abhijeeth Chandrasekaran |e author |
| 700 | 1 | 0 | |a Nelson Kinnersley |e author |
| 700 | 1 | 0 | |a Pavithra Ramesh |e author |
| 700 | 1 | 0 | |a Lu Zhang |e author |
| 700 | 1 | 0 | |a Fran Brown |e author |
| 700 | 1 | 0 | |a Vis Niranjan |e author |
| 245 | 0 | 0 | |a Exposure-response analyses of efzofitimod in patients with pulmonary sarcoidosis |
| 260 | |b Frontiers Media S.A., |c 2023-10-01T00:00:00Z. | ||
| 500 | |a 1663-9812 | ||
| 500 | |a 10.3389/fphar.2023.1258236 | ||
| 520 | |a 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 | ||
| 546 | |a EN | ||
| 690 | |a efzofitimod | ||
| 690 | |a pulmonary sarcoidosis treatment | ||
| 690 | |a exposure-response relationship | ||
| 690 | |a steroid-sparing effect | ||
| 690 | |a forced vital capacity | ||
| 690 | |a King's Sarcoidosis Questionnaire-Lung | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Frontiers in Pharmacology, Vol 14 (2023) | |
| 787 | 0 | |n https://www.frontiersin.org/articles/10.3389/fphar.2023.1258236/full | |
| 787 | 0 | |n https://doaj.org/toc/1663-9812 | |
| 856 | 4 | 1 | |u https://doaj.org/article/3f7393ecf74b4edbbe2b6fa84a82a5d3 |z Connect to this object online. |