On this episode of Molecular Moments, Jim McNally, Ph.D., speaks with Adam Stasio, president of SciMed, whose mission is to
Assays for the detection of neutralizing antibodies (NAb) provide a greater depth of insight into the safety and efficacy of biologic drug candidates by assessing potential drug inhibition. By binding to the drug, NAbs can inhibit the drug’s pharmacological function via target binding prevention, thus reducing or neutralizing the drug’s clinical effect. Because of this, NAb assessment is an integral part of any large molecule development program.
With a veteran bioanalytical team that worked on some of the first cases of immunogenicity, BioAgilytix is comprised of experienced scientists who are skilled at differentiating NAbs from other anti-drug antibodies (ADAs) and analyzing their potential immune responses via robust assays developed and validated to your regulatory requirements.
Analyzing NAbs can provide a greater understanding of drug performance by offering deeper insight into the safety and efficacy profile of a given therapeutic candidate. As ADAs with neutralizing capacities, NAbs can bind to the biotherapeutic drug product administered and prevent it from fulfilling its intended therapeutic function, which can lead to altered pharmacokinetics and/or reduced or total lost drug efficacy.
NAbs can be developed against any biologic including therapeutics for gene and cell therapies. For example, for adeno-associated viruses (AAVs) commonly used as delivery vehicles for gene therapy, there can be a high presence of neutralizing antibodies (NAbs) against some AAV serotypes prior to and after the initiation of the treatment. These antibodies may impair their transduction efficacy and in consequence effect the efficacy of the treatment.
BioAgilytix is able to provide expert services for NAb analysis of biological therapeutics in any class of large molecule drugs.
In this case study, we discuss how the BioAgilytix team developed a cell-based assay to measure the presence of antibodies against the AAV9 serotype—a strain of AAV known to transduce most cell lines poorly—in patients for its gene therapy candidate in a clinical trial.
When evaluating NAbs as a part of an immunogenicity study, BioAgilytix always tailors our methods to the specific study needs. Typically a tiered approach is chosen based on a screening assay to detect the presence of ADA, followed by a confirmatory assay to determine true-positive ADA samples, and finally performing further characterization in order to pinpoint NAb responses among the total ADA responses. In some cases, this tiered approach might be modified due to the mode of action of the drug and prevalence of neutralizing antibodies. We provide different assay formats, techniques, and methods for the measurement of the neutralizing capacity of ADA, including cell-based assays and competitive ligand binding (inhibitory) assays (CLBA).
The selection of the most appropriate assay format depends mainly of the risk profile and the mode of action of the drug. While cell-based assays are recommended for high-risk biologics, a non-cell-based NAb assay can be used for low-risk profile drugs with blocking ligand activity. BioAgilytix generally follows US Food and Drug Administration (US FDA) and European Medicines Agency (EMA) recommendations to select the appropriate platform.
BioAgilytix is able to develop and validate cell proliferation, biomarker, gene expression, gene reporter, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement dependent cytotoxicity (CDC) assays that meet NAb detection requirements with high specificity and selectivity, sensitivity, and precision.
BioAgilytix is committed to providing the highest quality bioanalysis for our customers’ NAb assessments, which we do by leveraging a variety of technology platforms. The advanced capabilities of these platforms are only enhanced by the skill of our seasoned scientific team, who are deeply experienced in optimizing them for each customer’s specific testing. The platforms we typically leverage are listed below.
Our expert Dr. Dominique Gouty offers insight into scientific and regulatory considerations for the development and validation of NAb assays used in biosimilar programs.
Every NAb assay is unique and should be based on a deep understanding of multiple factors such as the mechanism of action of the drug product, patient population, and drug development phase. BioAgilytix’s scientists are well-versed in how to develop suitable assays for NAb analysis based on these and other important considerations, ensuring you receive robust and accurate data on the immunogenicity potential of your therapeutic candidate, be it a biologic, gene therapy, cell therapy, biosimilar, or other class of large molecule drug.
Tap this expertise in both our USA and European labs, staffed with the teams and capacity needed to support any phase of study with premier, proven immunogenicity testing services.