PI-083 - POPULATION PHARMACOKINETIC ANALYSIS OF DUVAKITUG (TEV-48574) IN HEALTHY PARTICIPANTS AND PATIENTS WITH ASTHMA.

O. Dotan¹, D. Kang², A. Radivojevic³, R. Balyan², S. Rohatagi², R. Singh²; ¹Teva Pharmaceutical Industries Ltd., Netanya, HaMerkaz, Israel, ²Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States, ³intiGROWTH LLC, Miami, FL, United States.

Background: Duvakitug is a human IgG1 monoclonal antibody that binds to tumor necrosis factor (TNF) superfamily protein TNF-like 1A (TL1A). TL1A is implicated in inflammatory conditions such as inflammatory bowel disease (IBD) and asthma. TL1A signaling amplifies inflammation rather than driving immune response, making it a promising therapeutic target. The presented work aims to characterize the pharmacokinetics (PK) of duvakitug using data from trials in healthy participants and patients with asthma.

Methods: The analysis dataset comprised data from male and female participants from two phase 1 studies (total n=94) and one phase 2a proof-of-concept study in patients with asthma (n=33). No PK differences were observed between healthy participants and patients with asthma. Population PK (PopPK) modeling was used to describe changes in serum duvakitug concentrations over time. Variability in the observed profiles was assessed via covariate analysis and an attempt was made to test whether a set of demographic and baseline characteristics could explain the interindividual variability in selected PK parameters. PopPK models were assessed by evaluating individual and population mean parameter estimates (precision assessed by percent standard errors) and difference from the known priors or physiological values, and by graphical examination of standard diagnostic and population analysis goodness-of-fit plots. Analysis dataset preparation, exploratory analysis, and simulations were performed using appropriate R packages. Nonlinear mixed-effect modeling was performed using NONMEM.

Results: Among the several models evaluated, a one-compartment model with first-order absorption, linear elimination, body weight at baseline as a covariate on clearance, and volume of distribution best described the serum duvakitug concentration–time data.

Conclusion: The resulting PopPK model provides a quantitative platform for future PK analysis for duvakitug and will be used to inform alternative doses and regimens of subsequent studies in patients with IBD.
Disclosures: Duvakitug is being developed in an alliance partnership between two companies.