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Assessment of immunogenicity is a real challenge for the biotherapeutics industry. Every year at Immunogenicity at PEGS we present NEW findings and NEW case studies. Furthermore, we encourage NEW speakers to participate; from industry and from academia, including regulatory experts. In this track on Immunogenicity Assessment and Clinical Relevance, we present real examples of immunogenicity assessment in preclinical studies and in the clinic for a range of products, and examine the many challenges encountered and overcome. We also present recommendations for presenting immunogenicity data to the regulatory authorities.


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Recommended Pre-Conference Short Course* 

SC7: Immunogenicity Risk Assessment and Regulatory Strategies 

* Separate registration required.


WEDNESDAY, MAY 6

7:00 am Registration and Morning Coffee


Meeting Regulatory Expectations for Innovators and Biosimilars: Strategy and Assay Methodology for Challenging Products 

8:00 Chairperson’s Remarks

Boris Gorovits, Ph.D., Director, PDM, Pfizer, Inc.


8:10 KEYNOTE PRESENTATIONS

Recommendations for the Assessment and Reporting of Clinical Immunogenicity of Therapeutic Proteins and Peptides

Meena Subramanyam, Ph.D., Vice President, Translational Sciences, Biogen Idec, Inc.

To foster a unified approach to assessing and describing immunogenicity, the AAPS Therapeutic Protein Immunogenicity Focus Group convened a team of experts from the industry and regulatory agencies and tasked them with producing a consensus document comprising best practices and recommendations regarding: standardizing terminology; sampling schema for the assessment of ADA in clinical studies; interpretation and presentation of analytical data; and assessment of clinical impact.

8:40 Addressing Interchangeability and Extrapolation for Biosimilar Monoclonal Antibodies

Shefali Kakar, Ph.D., Senior Director, Clinical Pharmacology, Novartis Oncology Business Unit

The scientific, regulatory and legal principles for defining and implementing a biosimilar development are beginning to emerge globally. However, the primary expectation for obtaining an interchangeability or extrapolation label remains difficult in the absence of clear guidance from health authorities. Various case studies from approved biologics, including biosimilars will be presented. In this context, global differences in regulatory guidances on interchangeability and extrapolation will also be discussed.

9:10 Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients with Morquio A Syndrome: Results from MOR-004, a Phase 3 Trial

Case StudyBecky Schweighardt, Ph.D., Director, Immunogenicity Assessment, BioMarin Pharmaceutical, Inc.

Elosulfase alfa is an enzyme replacement therapy (ERT) for the treatment of Morquio A. In a 24-week phase 3 trial, all treated patients developed anti-drug antibodies, and the majority developed neutralizing antibodies (NAb) capable of interfering with cellular receptor binding in vitro. Despite the universal development of anti-drug antibodies, elosulfase alfa treatment was both safe and well tolerated and immunogenicity was not associated with lack of treatment effect.

9:40 Case Study on Characterization of Immunogenicity to Multiple Domain Biotherapeutics

Unpublished DataBoris Gorovits, Ph.D., Director, PDM, Pfizer, Inc.

An evaluation of an ADA response to an MDB based on drug risk factors, drug MOA, patient population and other parameters could facilitate prediction of safety consequences. This presentation will focus on a strategic approach to evaluation of MDB immunogenicity characteristics based on the program development requirements, including non-clinical and clinical translation. Potential issues and concerns will be discussed based on specific case studies.

10:10 Re-Assessment of Immunogenicity Risk based on Clinical Data: Case Study of a Humanized IgG1 Monoclonal Therapeutic with a Knob-and-Hole Structure

Mauricio Maia, Ph.D., Bioanalytical Sciences, Genentech, Inc.

Initial clinical immunogenicity evaluation plans are often based upon an immunogenicity risk assessment that includes a myriad of molecule and patient factors, but prior to attaining clinical experience. Clinical data can and should modify this assessment. This presentation will describe a case study of a structurally novel biotherapeutic whose risk-based assessment was changed following analysis of clinical immunogenicity data derived from early-stage trials.

10:40 Coffee Break in the Exhibit Hall with Poster Viewing


Neutralizing Antibody Assays  

11:25 Development of Neutralizing Antibody Assays for Antibody Therapeutics with Cell Depletion MOA

Shan Chung, Ph.D., Senior Scientist, Bioanalytical Sciences, Genentech – A Member of the Roche Group

Monoclonal antibodies with mechanisms of action (MOA) involving cell depletion have been used successfully in treatment of a variety of malignant diseases. This presentation will describe development of a neutralizing antibody (NAb) assay for a humanized therapeutic antibody that depletes target tumor cells via effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated phagocytosis (ADCP). A general guidance on selection of NAb assay format for antibody therapeutics will also be presented.

11:55 Driving Factors for Choice of Immunogenicity/NAb Strategy

Unpublished DataShalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

Currently a clear strategy for choosing a cell-based or non cell-based assay for the detection of anti-drug neutralizing antibodies is not available. This talk will provide an overview of an AAPS white paper currently being compiled that provides three rationales for selecting the NAb assay format. These include (i) the mechanism of action of the drug; (ii) the risk of NAbs on patient safety and (iii) assay characteristics of the NAb assay. When applied together these 3 aspects can guide the strategy of NAb assay format selection in a consistent manner for the vast majority of biological therapeutics.

12:25 pm Sponsored Presentation (Opportunity Available)

12:55 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own

1:55 Session Break


Overcoming Target Interference 

2:10 Chairperson’s Remarks

Meena Subramanyam. Ph.D., Vice President, Translational Sciences, Biogen Idec, Inc.

2:15 Case Studies on Troubleshooting Soluble Target Interference in Immunogenicity Assays in the Clinical Space

Case StudyQiang Qu, Ph.D., Senior Scientist, PDM, Pfizer, Inc.

Soluble targets that form multimers can result in false positive signals in bridging assays. This presentation will focus on troubleshooting clinical immunogenicity assays with interference from the soluble target multimers found in the circulation of the intended population. Two case studies will be presented with their own distinctive approaches to overcome the target interference, and a general mitigation strategy will be discussed for clinical immunogenicity assay development.

2:45 Strategy for Overcoming Target Interference throughout Development

Olivier Petricoul, Ph.D., Senior Investigator II, DMPK-PK/PD, Novartis Institutes for Biomedical Research

While drug interference is a well-known phenomenon for immunogenicity assays and is routinely characterized and optimized during the development and validation of the assays, interference by the pharmacological target occurs only under particular circumstances and is assessed on a case by case basis. This presentation will review different strategies for overcoming target interference, and case studies will be shown to illustrate how an integrated PK/PD/IG assessment can help to assess the clinical relevance of the immunogenicity assay.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:45 Problem-Solving Breakout Discussions

5:45 Networking Reception in the Exhibit Hall with Poster Viewing

7:00 End of Day


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THURSDAY, MAY 7

8:00 am Morning Coffee


Immunogenicity Assessment Challenges in the Clinic 

8:30 Chairperson’s Remarks

Shalini Gupta, Ph.D., Director, Clinical Immunology, Amgen, Inc.

8:35 Pre-Existing Antibodies: Are they always Meaningful?

Unpublished DataLakshmi Amaravadi, Ph.D., Senior Director, Translational Medicine, Biogen Idec, Inc.

The scientific community and the regulators alike have been performing investigations and evaluations to understand the relevance and potential impact of pre-existing antibodies on safety and efficacy. This presentation will review some of the considerations related to the evaluation of pre-existing antibodies, the experience so far and also present a case study to discuss the implications or lack thereof as it relates to detection of pre-existing antibodies.

9:05 Using Statistical Design of Experiment (DOE) in Assay Development to Reduce Drug Interference in Immunogenicity Assays

Sheng Dai, Ph.D., Principal Scientist, Biologics Clinical Pharmacology, Janssen Research & Development, LLC.

An acid dissociation approach is often used to overcome drug interference in immunogenicity assays for anti-drug antibody (ADA) detection. We utilize a statistical design of experiment (DOE) concept with nonhierarchical 4-Factor Split Plot design to thoroughly evaluate the effects of acid types, acid concentrations, temperature and duration of acidification of acid treatment conditions in the acid dissociation step of immunogenicity assays to improve drug tolerance and more accurately detect ADAs.

9:35 Advances in Improving Drug Tolerance of NAb assays

Christian Vettermann, Ph.D., Scientist, Clinical Immunology, Bioanalytical Sciences/PKDM, Amgen, Inc.

To achieve maximal sensitivity, NAb assays utilize a very low concentration of drug that can be easily neutralized by anti-drug antibodies. Therefore, exogenous drug contained in study samples is one of the most critical interference factors that can preclude NAb detection during the dosing phase. This presentation will focus on current approaches to improve drug tolerance of NAb assays through sample pretreatment and their limitations. The relevance of drug tolerance for the interpretation of study data will be discussed, and a novel strategy for detecting clinically impactful NAbs in the presence of high amounts of drug will be presented.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing


Demonstrating Safety of IgE AdaS:
Immune Complex Disease
 

11:05 Evaluation of Antibodies of IgE Isotype to Omalizumab and their Potential Correlation to Anaphylaxis

Case StudySally Fischer, Ph.D., Senior Scientist and Group Leader, Assay Development and Technology, Genentech, Inc.

To better understand the risk of anaphylaxis in patients with allergic asthma receiving regulatory-approved omalizumab, a recombinant humanized monoclonal antibody, a post-marketing pharmacosurveillance study was initiated in March, 2009. As part of this study, an assay was developed to detect antibody of IgE isotype to omalizumab. This presentation will discuss the challenges and approaches in development of this assay as well as the outcome of this post-marketing commitment.

11:35 Cynomolgus Monkey Case Study of Immune Complex Disease

Deborah Finco, Ph.D., Senior Principal Scientist, Drug Safety R&D, Pfizer, Inc.

We developed a method to induce immune complex glomerulopathy (ICG) in non human primaytes (NHPs) using BGG as the immunogen. The goal was to evaluate possible immune related biomarkers to detect early glomerular injury in non-human primates. We investigated: complement receptor 1 levels on erythrocytes; levels of circulating immune complexes complement split products, macrophage chemotactic protein 1, and anti- BGG antibodies. BGG dosing was associated with changes in CR1, CIC, anti-BGG titers and serum complement split products. The utility as biomarkers will be further discussed during the presentation.

12:05 pm Sponsored Presentation (Opportunity Available)

12:35 End of Conference

5:15 Registration for Dinner Short Courses



Recommended Dinner Short Course* 

SC11: Overcoming the Challenges of Immunogenicity Assessment 

*Separate registration required.


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