Utility of free and total target measurements as target engagement and efficacy biomarkers in biotherapeutic development-Opportunities and challenges

摘要: For biotherapeutics directed against soluble targets, most often monoclonal antibodies (mAbs), their therapeutic efficacy theoretically is driven by the magnitude and duration of free target suppression. However, for targets rapid turnover low abundance, it can be technically challenging to directly measure lowering following treatment with biologics. The opportunities, challenges, practical approaches assess bound utility measurements as biomarkers engagement are covered in this review. In particular, case examples presented illustrate interplay between drug free/bound target, how an integrated bioanalytical pharmacokinetic/target engagement/pharmacodynamic (PK/TE/PD) modeling approach used biologics turnover. Important caveats absence also discussed.