Neutralising Antibodies (NAbs)
Neutralising antibodies are anti-drug antibodies that bind a biologic at a site that blocks its pharmacological activity rather than merely speeding its clearance.
An anti-drug antibody is neutralising when it binds the molecule in a way that abolishes its pharmacological activity, rather than simply tagging it for faster clearance. The distinction is functional, not structural. A binding assay only establishes that an immune response exists; a neutralising assay asks whether the drug still works in the presence of patient serum, usually through a cell-based potency readout or a competitive ligand-binding format.
Rates track how foreign the sequence looks. Exenatide, a 39-residue exendin-4 analogue with no human counterpart, provoked antibodies in a large share of treated patients, and the minority carrying high titres showed a blunted glycaemic response. Analogues built on the human GLP-1 backbone are far quieter. Outside metabolism, neutralising antibodies to interferon beta in multiple sclerosis and factor VIII inhibitors in haemophilia are the textbook cases where the antibody, not the disease, decides whether treatment works.
That is why the result changes a decision rather than merely describing one. Loss of response on an unchanged dose is ambiguous on its own; a confirmed high neutralising titre makes escalation futile and argues for changing class rather than changing supplier. Comparative immunogenicity is also part of what a biosimilar sponsor must demonstrate before a regulator will accept interchangeability.
The usual misreading is comparing antibody percentages across labels. Assay sensitivity, drug tolerance and sampling schedules differ so much between programmes that the numbers sit on no common scale, and most positives are transient, low-titre and non-neutralising. The mirror-image error appears in grey-market discussion, where an unlicensed peptide is called non-immunogenic when the truth is that no assay has ever been run on it.