The challenge of new chemical entities attrition

Abstract

The pharmaceutical industry is facing many challenges to the successful delivery of new medicines from its research and development (R&D) efforts. Central to these productivity challenges is the declining survival of small molecule drug candidates from the preclinical stage through to Food and Drug Administration (FDA) approval and launch, despite the introduction of many new technologies and significant increases in R&D budgets. Only 50% of small molecules survive the preclinical stage, and only 1 in 16 of those that enter Phase I survive through to approval and launch. This contrasts with a 1 in 9 survival rate for biologics from Phase I through to approval and launch. Three key factors contribute to this diminishing survival rate. First, small molecules with poor physicochemical properties are closely associated with poor survival; second, many of the chosen biological targets for small molecules fail to produce meaningful efficacy in the disease; and third, the constant turmoil of strategy changes within pharmaceutical companies accounts for a surprisingly high rate of small molecule program failure. Each of the three key factors is reviewed, and recommendations for how to address each factor are explored.