Purpose Monoclonal antibodies target a single epitope or region in an antigen for therapeutic purposes. Given the highly mutant nature of SARS-COV-2 or coronavirus, it is likely that a cocktail of antibodies or a polyclonal antibody targeting multiple regions of the virus might be more beneficial in treating COVID-19. The purpose of this project, based on the reported clinical evaluation of XAV-19 polyclonal antibody in pneumonia patients, is to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to explain the relationship between drug concentrations and reduction in the nasopharyngeal viral load.
Methods: The concentration of the drug in a time course was related to the effect at each time point to determine the PK-PD relationship. Using Berkeley-Madonna, a PK-PD mathematical model including a central serum compartment, a peripheral effect compartment, and an Emax model for drug effects was developed to explain the observed drug concentrations and effects. Using published EC50 concentrations for XAV-19 and various variants of SARS-CoV-2, the time course of drug effect was predicted for the virus variants including D614G, alpha, beta, gamma, and delta.
Results: The results indicated a counterclockwise hysteresis loop for the PK-PD relationship, suggesting lower effects at the same concentration initially, followed by greater effects at the same concentration later. This is consistent with separation of the effect compartment from the serum compartment, where concentrations are measured. The model explained the observed data well.
Conclusion: The PK-PD model is useful in predicting dose-response relationships for the new polyclonal antibody. Further, it can be extended to other emerging variants of the coronavirus.