Overcoming disease specific matrix effects in a clinical pharmacokinetic assay
Etrolizumab is a humanized monoclonal antibody (mAb) with novel gut mucosal-selective lymphocyte anti-trafficking activity and has demonstrated to be capable of inducing clinical remission in ulcerative colitis (UC) patients in a Phase II clinical study. In the Phase III program currently underway, a second form of inflammatory bowel disease (Crohn’s Disease, or CD) is being studied, in addition to UC. Although the original PK ELISA assay was successfully validated in both normal human and UC sera and used for the phase I and phase II studies, attempts to matrix extend the ELISA for use in the CD population failed. This prompted additional work including optimization of the original ELISA and even re-development of the assay using different antibody pairs. Unfortunately, no substantive improvements were achieved, necessitating assay re-development using an alternative technology.
This webinar highlights the challenges Genentech, Inc. encountered with optimization/re-development of the original ELISA to overcome matrix interference in the CD population, and the qualification results of the new assay on the Gyrolab® platform.
- Development of an ELISA that can tolerate biological matrix in multiple indications can be challenging, requiring further optimization of the assay in each indication
- Challenges encountered with optimization/re-development of the original ELISA to overcome matrix interference in the disease population
- Qualification results of the new assay on the Gyrolab platform