Is there a best strategy for drug discovery?

Towards the end of the 1990s, several studies were undertaken to assess the efficiency with which the pharmaceutical industry was conducting its business. Most studies were content to report the metrics of drug discovery - essentially the numbers of compounds succeeding and failing in given time periods - but the exercise conducted by Anderson Brothers, in collaboration with most major pharmaceutical companies, sought to provide some predictive power to the figures generated. Briefly, the study concluded that a medium sized organisation with an annual turnover of approximately $5 billion would need to launch 3 new molecular entities each year to maintain a 10% growth rate.

The report went further and, based upon known attrition rates, predicted that for these production rates to be achieved, a company’s development pipeline would number between 15-30 products at any one time. The numbers of discovery projects required to feed this cycle, were similarly calculated from industry average failure rates. Over a four year period, the guarantee of 3 NMEs per year equated to a range of 150 - 300 discovery projects with 38 - 75 being completed each year. ("Completed" in this sense equates to transition to development or cessation.) These astonishing revelations were countered by the comments that the numbers in the pipeline could be markedly reduced through the delivery of "development ready" products from drug discovery departments.

It was surely no accident that comments and conclusions from the above study (and others) coincided with a technological revolution within the industry. The sequencing of the human genome was not only nearing completion but had spawned a number of techniques through which novel proteins (and, therefore, potential drug targets) could be identified. From the chemical laboratories there emerged the capabilities of combinatorial chemistry and later, those of parallel synthesis. The biochemists matched the production rates of the chemists with high throughput screening.

In response to the request for "development ready" compounds, high throughput biopharmaceutical methods were established to assess drug delivery properties (eg cell absorption assays, metabolic stability assessments, high througput analytical methods). Equally, there was the development of early safety studies designed to identify mutagenicity and cytotoxicity, and methods aimed towards the detection and categorization of structural toxophores.
Now, 5 to 6 years on from these initiatives it is timely to assess the improvements in drug discovery which have become established. The Society has gathered a singularly distinguished panel of speakers to comment upon the impact that the recent years have had. Has the rate of drug discovery increased? Have we become more incisive? What is being done well and what not so well and how do we measure these parameters? These are the questions that will form the focus of the day. We hope that you enjoy it.

For and on behalf of the Society for Medicines Research