Anti-drug Antibody Sample Testing and Reporting Harmonization.

A clear scientific and operational need exists for harmonized bioanalytical immunogenicity study reporting to facilitate communication of immunogenicity findings and expedient review by industry and health authorities. To address these key bioanalytical reporting gaps and provide a report structure for documenting immunogenicity results, this cross-industry group was formed to establish harmonized recommendations and a develop a submission template to facilitate agency filings. Provided here are recommendations for reporting clinical anti-drug antibody (ADA) assay results using ligand-binding assay technologies.

Correction to: Development and Utility of an ELISA Method for Sensitive and Specific Detection of IgE Antidrug Antibodies.

During the production process, the author order of Zhandong Don Zhong and Lynn L. Jiang were inadvertently placed. Lynn L.

Development and Utility of an ELISA Method for Sensitive and Specific Detection of IgE Antidrug Antibodies.

Biologics can potentially induce unwanted immune responses, leading to formation of antidrug antibodies (ADA) of various affinity, isotypes, and subclasses. Among them, antigen and drug-specific immunoglobulin E (IgE) antibodies have been reported to have potential correlation with hypersensitivity and anaphylaxis in particular. Recent regulatory guidance on immunogenicity testing has recommended the measurement of antigen-specific IgE antibodies for biologics with a reported high risk of anaphylaxis using assays with sensitivities in the high pg/mL to low ng/mL range.

Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program.

Enhancing efficiency and quality of statistical estimation of immunogenicity assay cut points through standardization and automation.

Biotherapeutics can elicit immune responses, which can alter the exposure, safety, and efficacy of the therapeutics. A well-designed and robust bioanalytical method is critical for the detection and characterization of relevant anti-drug antibody (ADA) and the success of an immunogenicity study. As a fundamental criterion in immunogenicity testing, assay cut points need to be statistically established with a risk-based approach to reduce subjectivity.

A phase I, open-label study of trebananib combined with sorafenib or sunitinib in patients with advanced renal cell carcinoma.

Background: Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.

Patients And Methods: This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.

Development of a biosensor-based immunogenicity assay capable of blocking soluble drug target interference.

As with other protein therapeutics, trebananib (AMG 386), an investigational peptide Fc-fusion protein ("peptibody") that inhibits angiogenesis by neutralizing the interaction of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) with the Tie2 receptor, has the potential to trigger an immune response in cancer patients treated with the therapeutic. An electrochemiluminescence bridging anti-drug antibody (ADA) assay that was utilized to support early-phase clinical trials in the development of trebananib was found to lack adequate sensitivity and drug tolerance in later-phase clinical studies when higher doses of trebananib were administered. Therefore, we developed a surface plasmon resonance (SPR) immunoassay method utilizing a secondary confirmatory detector antibody (goat anti-human IgG F[ab']2) known to cross-react with human IgG and IgM to better assess the potential impact of immunogenicity on the pharmacokinetics, pharmacodynamics, and toxicity of trebananib.

Identification and inhibition of drug target interference in immunogenicity assays.

A well-designed anti-drug antibody (ADA) immunoassay is critical for appropriately monitoring the immunogenicity profile of a therapeutic protein during its development. AMG 386 is a peptide-Fc fusion protein that inhibits angiogenesis by preventing the interaction of angiopoietins with the Tie2 receptor. In bridging immunoassays for ADA, interference by the drug target, present in the assay sample, can result in false positive antibody detection.