Immunogenicity Assessment and Clinical Relevance
Day 1 | Day 2 | Combined Session | Download Brochure
Part One | Part Two
ABOUT PART ONE: IMMUNOGENICITY ASSESSMENT AND CLINICAL RELEVANCE
Part One at CHI’s Immunogenicity Summit 2012 focuses on different types of immunogenicity assay, on evaluation of the results in terms of screening and confirmatory cut points, on handling drug interference and pre-existing antibody, and the impact of anti-drug immune complexes, and non-IgE hypersensitivity. It will include case studies on the relationship of anti-drug antibodies to PK, PD, safety and efficacy, including a case study for a novel biotherapeutic, and look at the impact of immunogenicity on clinical risk assessment.
WEDNESDAY, October 10
7:30 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Josi Holz, M.D., CMO, Ablynx NV
8:35 Drug Interference in Neutralizing Antibody Assays: Attempts at Overcoming the Challenge
Marie T. Rock, Ph.D., Vice President, Protein Bioanalysis, Midwest BioResearch LLC, a Wil Research Company
In order to fully characterize and gain an understanding of the nature of the immune response a cascade of analytical methods are used in a stepwise sequence. The final assessment involves the evaluation of the possible neutralizing activity of anti-drug antibodies that may be present. Generally these assays are cell based methods that respond to the biological activity of the drug. As a result they tend to be less sensitive than the typical immunogenicity panel of methods, but more importantly they are far more susceptible to drug interference. These drug effects will be demonstrated using case studies to show some possible approaches to minimize the impact of circulating drug.
9:05 Different Technology Platforms that Address Challenges Faced for the Development of Fit for Purpose Immunogenicity Assays
Maureen Deehan, Ph.D., Head, Pharmacology, Experimental Science & Translational Medicine, NovImmune SA - Biography
There are multiple formats available for anti-drug antibody assays. Thus, precision, accuracy, propensity for drug/target interference, cost of reagents and assay throughput must be considered when choosing a format. A case study involving a therapeutic antibody and comparison of results from different formats will be presented. Also work within the framework of the European Immunogenicity Platform will be discussed.
9:35 Impact of Analytical and Biological Variability on Observed Outcomes from Tiered Immunogenicity Assays
Robert J. Kubiak, Ph.D., Research, Translational Science, MedImmune LLC - Biography
Insufficient evaluation of inherent analytical variability of an immunogenicity assay in context of biological variability of the target population as well as neglecting to take into account relationships between the screening and confirmatory cut points may lead to significant differences between the expected and observed positive rates from tiered analyses of samples from drug-naive patients. This talk will discuss how analytical variability impacts selection of screen and confirmatory cut points and affects the overall outcomes from tiered immunogenicity assays.
10:05 Talk Title and Speaker to be Announced
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Detection of Immune Complex Formation in Non-Clinical Studies and Implications for Clinical Risk Assessment
Steve J. Swanson, Ph.D., Executive Director, Medical Sciences, Clinical Immunology, Amgen, Inc. - Biography
When human therapeutics are used in non-clinical studies it is anticipated that the animals will mount a robust immune response. This immune response can result in a high concentration of circulating anti-therapeutic protein antibodies. When large doses of the protein therapeutic are administered, especially via the intravenous route, there is a potential for large immune complexes to rapidly form. Detecting these immune complexes can be challenging but is important in order to understand pathology findings in the animals.
11:45 Impact of a Pre-Clinical Generic ADA Assay Detecting Drug-ADA Immune Complexes on Drug-Development Programs
Priya Sriraman, Ph.D., Principal Scientist, DMPK, F. Hoffmann-La Roche - Biography
Evaluation of immunogenicity in pre-clinical toxicological studies is an integral part of biotherapeutics development programs. Animals being evaluated for toxicology have high levels of circulating drug. We describe a highly drug tolerant, generic ADA assay and its impact on understanding toxicological findings and active drug exposure. Three case studies will be presented spanning monoclonal antibody therapeutics as well as a non-mAb protein therapeutic, and cynomolgus monkey and rat as toxicological species.
12:15 pm Immunogenicity in Biotherapeutic Development
Murty Chengalvala, Ph.D., Program Director, Senior Scientist, Immunology Services, Covance - Biography
The potential immunogenicity of biotherapeutics is a high profile safety concern for industry and regulatory authorities. As a CRO that amasses experience with a wide variety of biologics and clients’ needs, Covance has unique vantage point on this topic. Various strategies for reagent generation and assay development will be discussed.
12:30 Title to be Announced
Jörgen Dahlström, Ph.D., MBA, Scientific Director, ImmunoDiagnostics, Thermo Fisher Scientific
12:45 Luncheon Presentation
(Opportunity available, please contact Tim McLucas, email@example.com)
2:15 Chairperson’s Remarks
Steven J. Swanson, Ph.D., Executive Director, Medical Sciences, Clinical Immunology, Amgen, Inc.
2:20 Relevance of Animal Models for Predicting the Immunogenicity of Therapeutic Proteins
Jack Ragheb, M.D., Ph.D., Principal Investigator, Immunology, Therapeutic Proteins, CDER/FDA - Biography
“Humanized” mice that fully recapitulate the human hematopoietic system may permit direct in vivo assessment of human immunogenicity to a therapeutic protein. This session will describe the nature, limitations, utility, and predictive value of in vitro and in vivo model systems. Case studies will illustrate how pre-clinical data and a risk-based assessment may help inform the probability of immunogenicity in humans.
2:50 Correlating ADA Data with Effects on PK, PD, Safety and Efficacy
Stephen Keller, Ph.D., Associate Director II, Pre-Clinical & Clinical Development Sciences, GPRD Abbott iotherapeutics Corp. - Biography
The development of anti-drug antibodies can have consequences in patients that range from relatively benign to (rarely) very serious. Establishing the clinical, pharmacokinetic, and pharmacologic relevance of ADA development in patients is a worthwhile line of investigation in many circumstances. But is this something that should be done routinely? If so, what’s the best way to analyze data to explore these relationships? This presentation will use case studies to highlight some of the history, techniques, and outcomes of investigations into the effects of ADA on PK, PD, safety, and efficacy of biotherapeutics.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:00 Immunogenicity: A Case Study from Pre-Clinical to Clinical
Deborah Finco, Ph.D., Immunotoxicology COE, Pfizer, Inc. - Biography
4:30-5:30 In-Depth Breakout Discussions - Detailed Agenda
Table 1: Challenges in Developing Neutralizing Antibody Assays
Moderator: Deborah Finco, Ph.D., Senior Principal Scientist, Immunotoxicology COE, Pfizer, Inc.
Table 2: Dealing with Pre-Existing Positive ADA Activity in Study Patients
Moderator: Jim McNally, Ph.D., Senior Principal Scientist, Pfizer, Inc.
Table 3: Practical Application of Immunogenicity Pre-Clinical Risk Assessment
Moderator: Paul Chamberlain, NDA Advisory Board
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.
Table 5: Immunogenicity Testing During Clinical Trials
Moderator: Robert J. Kubiak, Ph.D., Research, Translational Sciences, MedImmune LLC
Table 6: IgE Anti-Drug Assay Development and Validation
Moderator: Jörgen Dahlström, Ph.D., MBA, Scientific Director, ImmunoDiagnostics, Thermo Fisher Scientific
Table 7: Relevance of Animal Models for Predicting the Immunogenicity of Therapeutic Proteins
Jack Ragheb, M.D., Ph.D., Principal Investigator, Immunology, Therapeutic Proteins, CDER/FDA
5:30-6:30 Welcome Reception in the Exhibit Hall with Poster Viewing
6:30 End of Day One of Immunogenicity Assessment and Clinical Relevance
Day 1 | Day 2 | Combined Session | Download Brochure
Part One | Part Two