Death of the ‘Blockbuster’and ‘Pivotal’ Clinical Trial: Rethinking the Drug Development Process

Abstract

Unprecedented developments in genomics, proteomics, immunology and cellular biology have promised a plethora of new targets for pharmacotherapy. The hope has been that targeting pharmacotherapy to the individual patient based on the molecular characteristics of their diseases and/or genetic polymorphisms relevant to drug metabolism and toxicity will lead to superior clinical outcomes. But while this promise has been realised in the treatment of a limited range of malignant disorders (such as chronic myeloid leukaemia), for the most part pharmacogenomics has failed to impact significantly on the major chronic diseases of the developed world, particularly neurological and cardiovascular diseases. In fact, those tracking the performance of the pharmaceutical industry have observed that despite the promise of a ‘genomic revolution’, the ‘pipeline’ of new drug registrations has been reduced to a ‘trickle’. At the same time, the cost of bringing a medicine to market has ballooned, a recent estimate for a new chemical entity was US$1.3 billion in 2005 dollars. The risks involved for the pharmaceutical and biotechnology industries are astounding, of every 5 to 10 thousand discovery compounds, around 250 enter pre-clinical workup, 5 make it to ‘first-in-man’ studies, and only one of these will make it through clinical development, with the chance of success declining yearly.