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?