Early specificity testing is crucial for the safety of antibody drugs

Integral Molecular, a leader in antibody discovery and characterization, has published new research results in the journal mAbsIt was found that up to one-third of antibody-based drugs exhibit nonspecific binding to unintended targets.

Off-target binding of drugs is a serious problem and a significant cause of adverse events in patients, which can even lead to death. Analysis of antibody off-target binding at different stages of clinical development suggests that this is a major cause of drug attrition. Early specificity testing could improve drug approval and patient safety.

In this study, Norden et al. present the first empirical assessment of antibody specificity and quantify the prevalence of off-target binding across the drug pipeline through retrospective specificity analyses of leading antibody candidates from biopharmaceutical companies and a prospective study of clinically administered antibody drugs (including those administered to patients in advanced clinical trials, approved by the FDA, or withdrawn). The molecules were tested using the Membrane Proteome Array™ (MPA), a cell-based protein array representing the human membrane proteome designed to test specificity and improve drug safety.

Important findings (Norden et al., mAbs)

• 18% of the 83 clinically administered antibody drugs tested showed off-target interactions.
• 22% of antibody drugs withdrawn from the market, often for safety reasons, showed nonspecific binding.
• 33% of the 254 lead molecules tested showed nonspecific binding, an indicator of failure at later stages of development.

These findings challenge the long-held belief in the absolute specificity of antibodies and underscore the urgent need for more rigorous testing.

Non-specific drug binding can lead to side effects or even death. The assumption that every antibody has absolute specificity is simply not accurate. New technologies such as MPA enable a detailed assessment of antibody specificity and can significantly reduce the risks in drug development.”

Diana Norden, PhD, Principal Investigator, Senior Research and Communication Scientist, Integral Molecular

About the Membrane Proteome Array™

Integral Molecular's Membrane Proteome Array™ is the industry-leading antibody specificity testing technology used by hundreds of customers worldwide. The MPA assesses the binding of approximately 6,000 proteins representing the entire human membrane proteome. Each protein in the array is individually represented in its biological conformation. MPA processes are ISO 9001 certified and its specificity data has been recognized by regulatory agencies worldwide, including the FDA. The MPA is currently under review by the FDA for approval as an approved drug development tool.