Immunogenicity
The ability of a therapeutic peptide to provoke an unwanted immune response, potentially leading to formation of anti-drug antibodies that reduce effectiveness or cause allergic reactions. Immunogenicity risk depends on the peptide's similarity to endogenous hormones, route of administration, and impurity profile.
Technical Context
Immunogenicity risk factors include: non-human sequences (lower homology to endogenous peptides increases risk), route of administration (SC > IV > topical for immunogenicity), impurities and aggregates (misfolded peptides and HCP contaminants act as adjuvants), dose and frequency (higher doses and more frequent administration increase risk), patient factors (genetic predisposition, immune status). Assessment uses a tiered approach: screening assay (sensitive but less specific — detects binding antibodies) → confirmatory assay (verifies true positives) → neutralising antibody assay (determines functional impact) → titre determination. Regulatory guidance (FDA 2014, EMA 2017) requires immunogenicity assessment throughout clinical development. For approved peptide drugs, ADA incidence ranges from <1% to >50% depending on the compound.