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The Successes and Limitations of Preclinical Studies in Predicting the Pharmacodynamics and Safety of Cell-surface Targeted Biologics in Patients

, : The Successes and Limitations of Preclinical Studies in Predicting the Pharmacodynamics and Safety of Cell-surface Targeted Biologics in Patients.

To improve drug development outcomes, it is important to review when preclinical pharmacodynamic and safety models have successfully predicted human responses and when they have not. Bugelski and Martin examine the concordance between preclinical and human data for biopharmaceuticals targeted to cell-surface proteins. The cases are interesting and several trends emerge. The pharmacodynamics of biopharmaceuticals in non-human primates (NHPs) is largely predictive; the use of surrogates in rodents may be similarly predictive, allowing for more conservative use of NHPs. And while overall concordance of preclinical toxicology data and clinical safety was poor, this is largely a reflection of the immunomodulatory biology of the majority of the biopharmaceuticals evaluated. The examples show that adverse effects in animals that were the result of direct and/or exaggerated pharmacology were modeled well, but that specific infections or other indirect outcomes of immunomodulation, along with cytokine-related events, were not modeled well in preclinical studies.


DOI: 10.1111/j.1476-5381.2012.01916.x

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