Assays for the detection of “anti-drug antibodies” (ADA) facilitate understanding of potential immune responses to biologic drug candidates, and determining the presence of ADAs and evaluating their clinical implications are a necessary part of any large molecule development program.
As one of the first teams to be involved in the initial cases of immunogenicity, BioAgilytix leverages extensive first-hand experience to deliver industry-leading expertise and services for ADA analysis and characterization, helping to accurately determine the immunogenic profile, safety, and efficacy of your therapeutic candidate.
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Ultimately, all biopharmaceuticals are immunogenic and may induce ADAs. The clinical effects of ADA formation can be highly variable and may cause severe adverse events that put the patient at risk. It is therefore imperative, both to guide drug development decision-making and as a regulatory requirement, to develop and validate ADA assays with the appropriate sensitivity, specificity, and selectivity for detection.
Since ADA responses can affect the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of a therapeutic candidate, ADA assays should be designed to detect antibodies that could mediate hypersensitivity responses or that have the ability to interfere with interactions between the therapeutic and its target for a neutralizing effect. This is particularly true for complex multicomponent drug modalities like those used in gene therapies. Each part of a gene therapy compound – the vector, cargo, and therapeutic protein encoded by the nucleic acid – can trigger a distinct immune response. A thoughtful and tailored approach is therefore required to address the complexities of assessing antibody-mediated immune responses of gene therapeutics.
FEATURED CASE STUDY
See how the BioAgilytix team designed a solid approach to overcome the challenge of target interference in an ADA assay to validate that the high rate of putative immunogenicity was due to target dimerization rather than drug-induced antibodies.
At BioAgilytix, we typically perform ADA analysis in a tiered-based approach, tailored to each specific project and based on an evaluation of many factors such as the presence of pre-existing antibodies and cross-reactivity of ADA of different isotypes.
The analytical cascade starts with a sensitive ADA screening resulting in a 5% false positivity rate for clinical use.* The determination of the cut point, with the help of statistical methods, is a complex and crucial step in this process. Positively screened samples must be re-analyzed in a confirmatory assay, and confirmed positive ADA samples may be further characterized for their titer, neutralizing capacity, binding affinity, isotyping, and other characteristics.
For example, it might be helpful to know the isotype of the ADA. IgM ADA may be an early marker of ADA formation, and the presence of IgE antibodies indicates an allergic reaction against the drug. In addition, the measurement of IgG subclasses may be supportive for the biological activities of ADA since in humans, IgG1 and IgG3 are mainly involved in complement activation and are more prone to NK cell recognition. The measurement of binding affinities of ADA is also informative for the ADA response interpretation. Since immunoassays are end-point analyses, the availability of kinetic parameters enables a comparative analysis of ADA and their biological relevance.
BioAgilytix’s ADA assays are fully validated in compliance with GLP regulations for use in pre-clinical and clinical studies.
*Other false-positive values for the screening cut point may be applied for non-clinical purposes.
ADA assessment can be conducted on variety of bioanalytical platforms, which our veteran staff and immunogenicity experts are adept at operating. Guided by deep firsthand experience performing immunogenicity testing, our team will select and optimize the most appropriate technology for your specific therapeutic candidate. The platforms we typically leverage are listed below.
ELISA
MSD-ECL (Electrochemiluminescence)
Flow Cytometry
Biacore (SPR)
ImmunoCAP
BioAgilytix’s Dr. Arno Kromminga and Dr. Lydia Michaut’s answer key questions on challenges and trends in the immunogenicity assessment of gene therapy compounds, such as the current regulatory requirements and where the therapeutic field is headed.
Whether evaluating antibody-mediated immune responses to biologics, gene therapy compounds, cell therapies, biosimilars, or any other class of large molecule drugs, BioAgilytix has the track record of experience, structured process, and scientific ingenuity required to successfully perform these complex assays. Our services for ADA assessment are available globally, with immunogenicity experts at both our USA and European labs. Turn to our team to deliver the data needed to assess the safety and efficacy of your promising drug candidate – data that is right on time and right the first time, to ensure you can confidently make decisions on your program and accelerate promising drug candidates through development to reach patients sooner.
See how our PK expertise complements our immunogenicity services by evaluating absorption, distribution, metabolism and excretion characteristics of a product.
Learn how we will translate our experience working with over 500 biomarkers in singleplex and multiplex formats to your project’s success.
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Services