Bioanalytical Assays in Support of Tanezumab Developmental and Reproductive Toxicity Studies: Challenges and Learnings

Abstract

Bioanalytical challenges were encountered during developmental and reproductive toxicity studies of tanezumab in cynomolgus monkeys. Possible changes in breast milk composition over the postpartum period potentially complicated assessment of tanezumab concentration in this matrix, requiring validation of the quantification assay across different time intervals. Immunogenicity assessment in maternal serum was complicated by apparent increases in the incidence of antidrug antibody-positive results in treatment-naive samples as pregnancy progressed that were due to changes in the concentration of nerve growth factor, tanezumab’s target protein. This was overcome by employing gestational day-specific cut points throughout pregnancy. Researchers should recognize potential challenges associated with dynamic matrices/physiological conditions and anticipate that assays developed under normal conditions may require adaptation for specialized situations.

Keywords:

• antidrug antibodies
• breast milk
• tanezumab
• toxicity
• toxicokinetics

Acknowledgments

The authors would like to thank the following individuals who helped perform the research described within the article: S Arrol (Pfizer), J McNally (Pfizer) and P Jardieu (ICON).

Financial & competing interests disclosure

This study was sponsored by Pfizer. S Hurst, T Clark and B Gorovits are full-time employees of, and own stock/options in, Pfizer. D Finco was an employee of Pfizer Inc. at the time the studies were conducted. D O’Neil and A Leskovar are employees of ICON plc, the research organization that was contracted by Pfizer to develop and validate the assays described in this manuscript (with the exception of the immunoaffinity lLC–MS/MS assay for NGF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by M Soulsby, PhD, CMPP of Engage Scientific Solutions and was funded by Eli Lilly & Co and Pfizer.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.