Prediction of Monoclonal Antibodies Pharmacokinetics in Human: Identification of a Reference Neonatal Fc Receptor (FcRn) Binding Affinity Using Physiologically Based Pharmacokinetic (PBPK) Modeling

Monoclonal antibodies (mAbs) are a cornerstone of modern medicine, but predicting their pharmacokinetics (PK) for First-in-Human (FIH) trials remains a significant challenge. A recent collaboration between Pharmetheus, Sanofi, and Aix-Marseille Université tackles this issue in biotherapeutic development. 

To address this, the team used the Open Systems Pharmacology open-source PBPK platform, PK-Sim, to analyze clinical data from 50 mAbs.

• The study identified 1.07 μM as reference Kd FcRn. 
• When applied to a test set of 15 mAbs, plasma exposure (AUC) was accurately predicted for 80% of the drugs, with a prediction error within the 0.80−1.25-fold range.
• For 100% of the test drugs, the predictions remained within a “2-fold” error range.
• By using human-derived reference value of Kd FcRn within PBPK framework, this approach aligns with recent initiatives to reduce unnecessary animal testing.

This work offers a standardized method that lets developers generate reliable PK predictions  early in development. By using a reference  ‘Kd FcRn value’ the industry can move from the lab to the clinic faster, with greater confidence and less reliance on animal testing. 

• Sanofi: @Salih Benamara, @Antoine Deslandes, @Laurent Nguyen, and @Donato Teutonico
• Aix-Marseille Université: @Salih Benamara and @Florence Gattacceca
• Pharmetheus: @Erik Sjögren and @Marylore Chenel