The AAPS Journal

, Volume 15, Issue 3, pp 852–855

Pre-Existing Biotherapeutic-Reactive Antibodies: Survey Results Within the American Association of Pharmaceutical Scientists

  • Li Xue
  • Michele Fiscella
  • Manoj Rajadhyaksha
  • Jaya Goyal
  • Claire Holland
  • Boris Gorovits
  • Alyssa Morimoto
Rapid Communication

Abstract

The immunogenicity profile of a biotherapeutic is determined by a multitude of product and patient-related risk factors that can influence the observed incidence and clinical consequences of immunogenicity. Pre-existing antibodies, i.e., biotherapeutic-reactive antibodies present in samples from treatment-naïve subjects, have been commonly observed during immunogenicity assessments; however their relevance in terms of the safety and efficacy of a biotherapeutic is poorly understood. An American Association of Pharmaceutical Scientists-sponsored survey was conducted to gather information about the prevalence, nature, and consequences of pre-existing antibodies in clinical and nonclinical studies. The survey results indicate that pre-existing antibodies against a variety of biotherapeutics (e.g., mAbs, fusion proteins) are frequently encountered, especially in the context of autoimmune diseases, but that the methods and approaches used to detect, characterize, and report these antibodies vary. In most cases, pre-existing antibodies did not appear to have clinical consequences; however, a few of the respondents reported having observed an effect on pharmacokinetic, pharmacodynamic, safety, and/or efficacy parameters. The findings from this survey are an important first step in evaluating the potential risks associated with the presence of pre-existing antibodies and highlight the importance of standardizing the approaches for detection and characterization of these antibodies. Cross-industry sharing of case studies and relevant data collection will help better inform biotherapeutic risk/benefit profiles and provide deeper understanding of the biological consequences of pre-existing antibodies.

KEY WORDS

immunogenicity risk pre-existing antibodies standardization 

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Li Xue
    • 1
  • Michele Fiscella
    • 2
  • Manoj Rajadhyaksha
    • 3
  • Jaya Goyal
    • 4
  • Claire Holland
    • 5
  • Boris Gorovits
    • 1
  • Alyssa Morimoto
    • 6
  1. 1.Pharmacokinetics, Dynamics & Metabolism (PDM-NBE)Pfizer Inc.AndoverUSA
  2. 2.Clinical ImmunoassaysHuman Genome Sciences Inc.RockvilleUSA
  3. 3.Bioanalytical SciencesRegeneron Pharmaceuticals Inc.TarrytownUSA
  4. 4.Department of Translational MedicineBiogen IdecCambridgeUSA
  5. 5.Clinical Immunology, Biopharm Research and Development UnitGlaxoSmithKlineKing of PrussiaUSA
  6. 6.Bioanalytical SciencesGenentechSouth San FranciscoUSA

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