Immunogenicity Summit Breakout Discussions

Breakout Discussions Part One, Wednesday October 10

Table 1: Challenges in Developing Neutralizing Antibody Assays

Moderator: Deborah Finco, Ph.D., Senior Principal Scientist, Immunotoxicology COE, Pfizer, Inc.

  • Factors for selection of cell-based Nab vs. non-cell-based Nab assays
  • Bioanalytical challenges
  • Challenges for Nab validation
  • Interpretation of the results and implications for risk assessment

Table 2: Dealing with Pre-existing Positive ADA Activity in Study Patients

Moderator: Jim McNally, Ph.D., Senior Principal Scientist, Pfizer, Inc.

  • Prediction of reactivity in naive samples vs. reactivity in pre-dose samples collected from study patients
  • If pre-dose samples with high levels of reactivity are identified, should we care? If so, what are the appropriate follow up activities?
  • Open exchange - what have you seen when characterizing pre-existing ADA and their impact?
  • What are the regulatory expectations for characterizing pre-existing ADA?

Table 3: Practical Application of Immunogenicity Pre-Clinical Risk Assessment

Moderator: Paul Chamberlain, NDA Advisory Board

  • Pertinent risk factors
  • Features of a good risk analysis and risk mitigation plan
  • Sharing of experiences of applying risk assessment in pre-clinical and clinical studies
  • How should we interpret bioanalytical signals relative to clinical significance?
  • Sharing experiences in presenting an immunogenicity risk assessment to the health authorities.

Table 4: Detection of Immune Complexes and Their Impact on Immunogenicity Assessment

Moderator: Steve J. Swanson, Ph.D., Executive Director, Medical Sciences, Clinical Immunology, Amgen, Inc.

  • Challenges of detecting ADAs in the presence of excess drug
  • Limitations of acid dissociation of immune complexes
  • Potential dangers of immune complexes in terms of toxicity and interpretation of immunogenicity
  • Can the drug be modified to prevent immune complex formation?
  • Immune complexes with PEGylated proteins
  • Sharing of experiences

Table 5: Immunogenicity Testing During Clinical Trials

Moderator: Frank F. Weichold, M.D., Ph.D., Director, Clinical Pharmacology and DMPK, Translational Science, MedImmune, LLC

  • Immunogenicity study design
  • When should immunogenicity assessments be made and how?
  • How do you select endpoints and interpret the results?
  • At which stage of the clinical trial will the cell-based neutralizing antibody assay be required?

Table 6: IgE Anti-drug Assay Development and Validation

Jörgen Dahlström, Ph.D., MBA, Scientific Director, ImmunoDiagnostics, Thermo Fisher Scientific

  • When it is appropriate to establish an IgE anti-drug assay associated with a clinical trial?
  • Unique challenges associated with IgE anti-drug assays (low concentration, interference from anti-drug of non-IgE isotypes and absence of positive controls)
  • Correlates with alternative IgE antibody assays (skin testing, provocation testing)
  • The role of heterologous interpolation in calibration and validation of IgE anti-drug assays

Breakout Discussions Part Two: Friday October 12

Table 1: Product-related Factors that Contribute to Immunogenicity

Moderator: Wim Jiskoot, Ph.D., Professor, Division of Drug Delivery Technology, Leiden University

  • Which structural variants increase immunogenicity?
  • How SVPs may impact immunogenicity, safety and efficacy
  • Comments on impact of formulation on SVPs and immunogenicity
  • Relation between formulation, dosing , packaging and immunogenicity
  • Measures to ensure long-term stability and avoid aggregation in protein drug products

Table 2: To what Extent can Immunogenicity Prediction affect the Clinical Strategy?

Moderator: Timothy Hickling, Ph.D., Associate Research Fellow, PDM Immunogenicity Sciences, Pfizer, Inc.

  • Understanding relative weight of immunogenicity risks through planning for product, delivery and patent factors.
  • Learning from examples of products with aggregation, degree of humanization, presence of T cell epitopes, formulation, etc
  • Pros and cons of in silico, in vitro and in vivo methods.
  • Which clinical measurements could be utilized to improve future predictions?

Table 3: Immune Tolerance Approaches

Moderator: Amy Rosenberg, M.D., Director, Therapeutic Proteins, CDER/FDA

  • When is immune tolerance induction indicated and in what clinical circumstances should it be considered
  • Factors that promote tolerance / promote immunogenicity.
  • Impact of dosing regimen and route on drug immunogenicity
  • Impact of formulation and formulation change on immunogenicity
  • Design of therapeutics for reduced immunogenicity

Table 4: Relevance of Animal Models for Predicting the Immunogenicity of Therapeutic Proteins

Jack Ragheb, M.D., Ph.D., Principal Investigator, Immunology, Therapeutic Proteins, CDER/FDA

  • Are relative immune responses (aggregated vs. non-aggregated human protein in a mouse) a valid measure?
  • How might known differences in the human and mouse adaptive and innate immune systems impact the results?
  • What, if any, is the role of adjuvants in such studies?



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