Kevin
The following is my opinion only:
From the context of your question, it is clear that you are distinguishing between pre-existing ADA (PEA) and treatment-emergent ADA (TEA). Indeed, this is important in order to understand the effect of the drug on the immune system. However, the reverse is not true; PEA might impact the drug just as much as TEA. If there are PEA present, I would think you would have an interest in knowing whether those are neutralizing. In an extreme case, AAV-based gene therapy, pre-existing neutralizing activity might even be an exclusion criterion.
So, in my opinion, ALL confirmed ADA-positive samples should be considered fair game for NAb testing. It might not be necessary to test every single sample, however. At a minimum you should test the predose and the end of study samples. In between those timepoints only if it is important to know at which point in time a neutralizing response emerged
------------------------------
John Kamerud Ph.D.
Principal
JK Bioanalytical Consulting LLC
Satellite Beach FL
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------
Original Message:
Sent: 01-23-2025 00:39
From: Kevin Carleton
Subject: Immunogenicity Testing | Sample or Subject Status --> Nab
Hello immunogenicity experts,
I am interested in hearing from the community on what the current industry best practice is with regards to progressing samples/subjects to further immunogenicity characterization testing in the neutralizing antibody (NAb) assay. Since I've joined my current organization, our position is that we only proceed with ADA positive samples from ADA positive subjects to the neutralizing antibody test. However, this requires that an assessment is made real-time whether the subject is treatment-emergent or treatment-boosted. And this real-time Subject Status could ultimately change over the duration of a study. My perception is that most bioanalytical teams are testing ALL positive ADA samples in the neutralizing antibody assay regardless of the Subject Status. Clearly, there are operational efficiencies to testing all positive ADA samples, but what are the considerations to not performing Nab testing on all ADA positive samples? Are the considerations for conflicting results (i.e. ADA negative subject with positive Nab results) that outweigh this efficiency?
------------------------------
Kevin Carleton
Scientific Director
Johnson & Johnson Innovative Medicine
Exton PA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------