Assessment of the Immunogenicity Potential for Oligonucleotide-Based Drugs.

Therapeutic oligonucleotides (ONs) have characteristics of both small molecules and biologics. Although safety assessment of ONs largely follows guidelines established for small molecules, the unique characteristics of ONs often require incorporation of concepts from the safety assessment of biologics. The assessment of immunogenicity for ON therapeutics is one area where the approach is distinct from either established small molecule or biologic platforms. Information regarding immunogenicity of ONs is limited, but indicates that administration of ONs can result in antidrug antibody formation. In this study, we summarize the collective experience of the Oligonucleotide Safety Working Group in designing the immunogenicity assessment appropriate for this class of therapeutic, including advice on assay development, clinical monitoring, and evaluation of the impact of immunogenicity on exposure, efficacy, and safety of therapeutic ONs.