Scientist, DMPK & BioA Denali Therapeutics South San Francisco, California
Sensitive, specific measurement of a soluble analyte in circulation is important for appropriately assessing pharmacodynamic response and monitoring patient safety. Challenges in assessing endogenous analyte levels arise when the analyte of interest is also a component of the multidomain therapeutic. An immune response consisting of anti-drug antibodies (ADA) can evolve and, subsequently, antibodies to the domain of the therapeutic that resembles the analyte can be induced. The presence of the therapeutic and ADA interferes or conversely affects the quantitation of the endogenous analyte, confounding the interpretation of the safety data. Using a combination of automation and solid phase extraction to remove the interfering drug and ADA, a high throughput, reliable and specific assay to quantitate the endogenous biomarker was successfully developed and validated. Endogenous levels with and without the presence of drug and ADA can aid in the surveillance of patient safety.
