Teplizumab-mzwv binds to CD3 (a cell surface antigen present on T lymphocytes) and delays the onset of Stage 3 type 1 diabetes in adults and pediatric patients aged 8 years and older with Stage 2 type 1 diabetes. The mechanism may involve partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes. Teplizumab-mzwv leads to an increase in the proportion of regulatory T cells and of exhausted CD8+ T cells in peripheral blood.
Clinical studies have shown that teplizumab-mzwv binds to CD3 molecules on the surface of both CD4+ and CD8+ T cells during treatment, with internalization of the teplizumab-mzwv/CD3 complex from the surface of T cells. Pharmacodynamic effects include lymphopenia in the absence of depletion of T cells with a nadir on the 5th day of dosing, during a 14-day course of teplizumab treatment. Teplizumab-mzwv exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of teplizumab-mzwv have not been fully characterized.
Steady state concentrations of teplizumab-mzwv are not expected to be achieved during the 14-day course.
The central volume of distribution (Vd) of teplizumab-mzwv was 2.27 L in a 60 kg subject.
Teplizumab-mzwv showed saturable binding and elimination. The mean (SD) terminal elimination half-life and clearance of teplizumab-mzwv are 4.5 (0.2) days and 2.7 (0.8) L/day in a 60 kg subject, respectively.
Teplizumab-mzwv is expected to be metabolized into small peptides by catabolic pathways.
No clinically significant differences in the pharmacokinetics of teplizumab-mzwv were observed based on age (8 to 35 years old), biologic sex, or racial groups (White, Asians).
BSA-based dosing normalizes the exposure to teplizumab-mzwv across body weight.
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