A Proposal to Redefine Clinical Immunogenicity Assessment.

Area of Science:

• Biotechnology and Pharmaceutical Sciences
• Immunology
• Clinical Pharmacology

Background:

• Over 100 therapeutic proteins (TP) have been approved since 2007, generating extensive clinical data on immunogenicity.
• Data reveal that anti-drug antibody (ADA) responses are not always clinically relevant, challenging current standard testing practices.

Purpose of the Study:

• To re-evaluate standard immunogenicity testing protocols for therapeutic proteins.
• To propose an optimized, event-driven immunogenicity testing strategy for low-risk TPs in early clinical development.

Main Methods:

• Review of clinical experience and immunogenicity data from approved therapeutic proteins.
• Proposal of an event-driven ("collect-and-hold") immunogenicity testing strategy for early-phase TP development.
• Emphasis on risk assessment and pivotal studies for definitive ADA impact evaluation.

Main Results:

• A significant portion of ADA responses observed in clinical trials lack demonstrable clinical relevance.
• The proposed strategy aims to reduce non-impactful testing, focusing resources on pivotal studies.
• Immunogenicity risk assessment remains a continuous, real-time process.

Conclusions:

• Current "standard practice" of routine ADA testing in all patients may be extraneous for certain therapeutic proteins.
• An event-driven testing approach for low-risk TPs can yield clinically relevant immunogenicity data efficiently.
• Optimized immunogenicity testing strategies are crucial for effective drug development while prioritizing patient safety.