Charcoal-Based Depletion Method to Improve Drug Tolerance in Neutralizing Antibody Assays for Therapeutic Peptides

Peptide based therapeutics such as GLP-1 analogs are an increasingly important therapeutic modality for metabolic diseases. As these therapeutics often mimic endogenous counterparts, assessing their immunogenicity during clinical development is critical for understanding safety and efficacy profiles and meeting regulatory expectations. Here, we describe a sample pretreatment strategy using activated charcoal to deplete residual drug and mitigate matrix interference, enabling development of drug-tolerant neutralizing anti-drug-antibody (nAb) assays. This approach was optimized and validated using Survodutide, a half-life extended GLP-1R/GCGR dual-agonist currently in clinical development. The optimized charcoal depletion improved assay drug tolerance by approximately 100-fold, facilitating reliable nAb detection in clinical samples. Ultimately, the method was successfully implemented in several validated nAb assays to support Survodutide clinical development. This platform approach has the potential for broad application across peptide therapeutics where drug tolerance is a critical challenge.