A Proposal to Redefine Clinical Immunogenicity Assessment

With more than 100 therapeutic proteins(TP) approved since the first EMA guidance on immunogenicityin 2007, a vast amount of clinical experience with a variety of therapeutic proteinshas been gained. This has provided data on anti-drug antibodies ( ADA) and their observed clinical impact, or lack thereof. It has become evident that not all ADAresponses are clinically relevant. The current “standard practice” is to test for ADAin all patients on every study. It is essential that we acknowledge the immunogenicitydata gained from marketed TPs and that options for immunogenicitytesting reflect this information. Improvements in bioanalytical support throughout the drug development processwill eliminateextraneous, non-impactful practices. We propose that low-risk therapeutic proteinscould be supported with an event-driven (“collect-and-hold”) immunogenicity testing strategythroughout early phases of the clinical program. In the absence of an event, only pivotal studies (where ADAincidence and impact can be decisively assessed) would include default ADAtesting. In keeping with the “standard practice,” immunogenicityrisk assessment must be an on-going and real-time evaluation. This approach has the potential to deliver meaningful, clinically relevant immunogenicityresults while maintaining an emphasis on patient safety.