Drug Development


An automated approach to solving Pharma’s cardiac toxicity conundrum


The pharmaceutical industry is facing ever-growing difficulties in developing new drugs and bringing them to market1,2. Many factors stand in the way of R&D productivity, not least of which are shrinking budgets. Yet one of the most pressing challenges continues to be the issue of ensuring that new drug candidates have an acceptable safety profile.


By Beppy van de


Waart, Dr Walter Westerink and Dr Nuria Piñeiro Costas


I


n an effort to avoid surprises far along the drug-development road, pharmaceutical com- panies are making it a priority earlier in the process to test for toxicity – especially for high- prevalence liabilities such as hERG cardiac toxici- ty3. But these tests are feasible only by using high- er throughput methods that demand a small amount of compound4. The recent introduction of automated patch clamp platforms that deliver high-quality data has enabled this much-needed hERG profiling earlier in drug discovery during lead optimisation, helping pharmaceutical compa- nies spend their resources wisely5.


This review discusses the application of auto- mated patch clamp platforms during lead optimi- sation and thoroughly explores advantages and disadvantages of various platforms in use today. Several examples from the evaluation of the auto- mated patch clamp platform CytoPatch (Figure 1)


60


at WIL Research, a global contract research organ- isation, are also shown.


The business risk of innovative drug candidates


Pharmaceutical companies spend tremendously on drug research and development, pouring resources into every phase: target finding, lead finding, lead optimisation, preclinical development, and Phase I- III clinical development. And that is before mar- keting costs are factored in. Yet, despite a marked increase in spending over the past decade, the industry is putting forth fewer new drug candidates; the number of applications filed to FDA’s Center of Drug Evaluation and Research declined to 23 in 2010 from 45 in 1996. Analysis of a database with 28,000 R&D proj- ects shows that the attrition rates in all phases of drug development have increased significantly2.


Drug Discovery World Spring 2013


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