The Application of HematoEogic and Hematopoietic Toxicology Investigation to Pharmaceuticals Discovery

摘要

A retrospective analysis of all causes of drug attrition due to toxicity at BMS shows approximately 8% to be due to primary unexpected or exaggerated hematologic or hematopoietic effects of drug candidates. Given the general rapidity with which such changes occur, the accessibility of blood and bone marrow to detailed analysis, and robust predictive techniques for evaluating potential effects of drugs on cells of the bone marrow and peripheral blood, these causes of drug candidate failure can generally be considered avoidable. When not readily predicted, appropriate predictive and diagnostic technologies are readily applied to counter-screens to improve potential hematologic liabilities in backup compounds. Such improvement assumes effects are not related to the molecular target of the desired pharmacology. Not infrequently, modulation of the target itself results in hematopoietic or hematologic change, the significance of which is evaluated in the context of risk and benefit for each separate disease indication.