Drug discovery is an expensive and risky business. Some 95 percent of drugs tested in Phase I clinical trials do not reach market. It has been shown that a research environment conducive to closer collaboration between scientists and clinicians can produce earlier ‘go-no-go decisions’, as they’re called, and reduce the failure rate of drugs, known as the drug attrition rate. I recently caught up with some members of an extraordinary team who are making smarter drugs to outsmart cancer a reality for cancer patients across the UK.
The Drug Development Unit is a joint initiative between The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, to decrease drug development times and reduce attrition rates by providing a route from pre-clinical development through to the clinic.
What makes this Unit so special? It provides the physical space that allows scientists and doctors to work together on a daily basis. This pioneering set-up means that together researchers can plan clinical trials for a promising new drug compound before the compound has completed pre-clinical testing – potentially shaving years off drug development times.
The Unit recently opened its doors to members of the public, patients and their families, and I was fortunate enough to be there to see how drugs developed in the laboratory are seamlessly being translated into the clinic to benefit patients. Using the latest kit, including, x-ray crystallography, Next Generation Sequencing and mass spectrometry, researchers are gaining insight into the mechanisms driving cancer, which is helping them identify drug compounds which target particular molecular drivers of cancer development. Doctors then develop specific clinical trials to test the target drug, and in turn these results provide our scientists with valuable knowledge about how the drug behaves in the patient, allowing them to complete the loop by modifying their next set of experiments accordingly. Closing this loop of information flow is vital to improving drug discovery and development.
Abiraterone, a life-extending drug to treat patients with advanced prostate cancer, discovered at The Institute of Cancer Research (ICR), was approved by the FDA in 2011. Now marketed as Zytiga, the drug has become the most-used first-line treatment for advanced prostate cancer patients in the world. Zytiga was jointly developed by the ICR and The Royal Marsden, and took six years from Phase I clinical trial to registration. While this is a fantastic achievement, the Drug Development Unit wants to reduce future drug development times and make the process more cost-effective.
The need for improved drug development was recently highlighted by Professor Andrew Pearson, Cancer Research UK professor of paediatric oncology at the ICR and a paediatric consultant at The Royal Marsden, in a review published in Expert Opinion on Drug Discovery. He identified three pillars for reducing drug attrition rates – improved pre-clinical models for better prediction, improved clinical trials to better understand the effect of the drugs on a patient, and increased collaboration to combine strengths between industry, academia and regulators.
The Drug Development Unit is an example of a model meeting these criteria, and as such is moving away from older, linear innovation models where commercialisation of outcomes was not considered until late in the process. The ‘Valley of Death’, a high-risk phase between the completion of pre-clinical research and the launch of clinical trials, is where a large proportion of drug development projects fall foul, and is one of the reasons why so many new compounds never reach market. The Drug Development Unit is certainly not immune to the ‘Valley of Death’, but its collaborative approach – with the goal of successful drug development being identified at the start of the project – does seem to be paying dividends.
Will there ever be a cure for cancer? With cancer in reality being consisting of hundreds of genetic sub-types, few researchers expect to stumble on a single big bang cure for the disease. But new-style smart drugs are already prolonging lives for individual cancer patients, and combinations of treatments hold real promise for the future. One thing we can be sure of, the Drug Development Unit is having a positive effect on patients today, right here, right now.
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