New horizons in toxicity prediction: supporting pharmaceutical development

Academics: Professor P. Johnson, A. Long,  J. Vessey, W. Button, N. Greene, M. Patel,  C. Marchant, Dr J. Langowski, P. Judson, Faculty of Maths and Physical Sciences

Toxicology prediction software, initially developed in the University of Leeds, has changed the pharmaceutical industry by reducing the resources and time needed to launch new drugs, resulting in increased revenues.

The Association of British Pharmaceutical Industry estimate the total cost of getting a new drug to market is £1.15bn so the industry is keen to find ways to reduce these costs.The ability to predict potential significant toxicity of pharmaceutical impurities is of vital importance to the pharmaceutical industry because many drug candidates fail in development due to toxicity problems. Early identification of toxicity  can prevent the costs associated with unnecessary research and development, reducing development costs by an average of £30m over five years.  It can also help reduce the likelihood of late failure of drug candidates and reduce the use of animals in drug development.

A heritage of chemical informatics

A long-running collaboration involving Leeds researchers and partners from the chemical and pharmaceutical industries led to the establishment of Lhasa Ltd and to the development of a knowledge-based system to predict the potential toxic hazards of individual organic chemicals. This software, now known as Derek Nexus has been made widely available by Lhasa.

A study by in collaboration with FRAME (Fund for the Replacement of Animals in Medical Experiments) highlighted the accuracy and reliability of Derek Nexus and drove a new phase of the model’s refinement. Research in Leeds also created Meteor Nexus, a complementary system which addresses a key gap in toxicity prediction by identifying metabolic routes which might lead to toxic metabolites 

Faster to market, increasing revenue and benefiting patients

The US Food and Drug Administration (FDA) has cited Derek Nexus as a recommended prediction tool in 2008 guidance on reducing the potential lifetime cancer risk associated with patient exposure to genotoxic and carcinogenic impurities both during clinical development and after approval.

As a result of the success of Derek Nexus in predicting toxicity risk, the software has been universally adopted by the pharmaceutical sector and embedded in the workflow industry-wide. These changes have increased revenues from launched drugs by extending their patent period of exclusivity (estimated at a revenue increase of £150M over five years) and reduced costly and time consuming experimental investigation (estimated cost saving of £30M over five years), whilst still ensuring patient safety regulations are met.

Lhasa has 254 member organisations, including the top 20 pharmaceutical companies in the world and over 80 highly qualified staff. The company recently reported revenues over £5.4M, with Derek Nexus contributing 56% and other more recent products based on Leeds research providing major contributions.

Lhasa Limited is a not-for-profit company and educational charity that facilitates collaborative data sharing projects in the pharmaceutical, cosmetics and chemistry-related industries.

Funder: LHASA UK