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Assessment of the Immunogenicity Potential for Oligonucleotide-Based Drugs

Scott P Henry1, Cecilia Arfvidsson2, Josh Arrington3

  • 1Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.

Nucleic Acid Therapeutics
|September 30, 2022
PubMed

Insights

Therapeutic oligonucleotides (ONs) can trigger antidrug antibody formation. This study provides guidance on assessing ON immunogenicity, covering assay development, clinical monitoring, and impact evaluation for safer drug development.

Area of Science:

  • Pharmacology
  • Immunology
  • Drug Development

Background:

  • Therapeutic oligonucleotides (ONs) possess unique properties, bridging small molecules and biologics.
  • Current safety assessments for ONs often adapt small molecule guidelines, but unique characteristics necessitate biologic safety concepts.
  • Immunogenicity assessment for ON therapeutics requires a distinct approach compared to traditional platforms.

Purpose of the Study:

  • To summarize the Oligonucleotide Safety Working Group's experience in developing immunogenicity assessments for therapeutic ONs.
  • To provide recommendations for assay development, clinical monitoring, and evaluation of immunogenicity's impact.
  • To address the limited information on ON immunogenicity and antidrug antibody formation.

Main Methods:

  • Review of collective experience from the Oligonucleotide Safety Working Group.
  • Development of guidelines for immunogenicity assessment strategies.
  • Focus on assay design, clinical surveillance, and impact analysis.

Main Results:

  • Administration of therapeutic ONs can lead to antidrug antibody (ADA) formation.
  • Established methodologies for immunogenicity assessment need adaptation for ON therapeutics.
  • A framework for evaluating the clinical implications of ON immunogenicity is proposed.

Conclusions:

  • Immunogenicity assessment for therapeutic oligonucleotides is critical and distinct.
  • Standardized approaches are needed for assay development and clinical monitoring.
  • Understanding and managing ON immunogenicity is key to ensuring therapeutic efficacy and safety.
Keywords:
antidrug antibodiesimmunogenicity testingoligonucleotides

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