The Need for Predictive Toxicology



Pharma IQ
11/17/2011

With the growing cost of drug discovery and development, organisations involved in the manufacture of pharmaceuticals are keen to do all they can to avoid the huge costs associated with late-stage drug attrition. Current figures suggest that the average cost of bringing a drug through screening, chemistry, pre-clinical development and testing has now reached close to $900 million (£559 million), so pharmaceutical companies will use all the technology available to them to avoid the risk of failure, with predictive toxicology considered to be a major tool at their disposal.

Predictive toxicology works by giving research and development teams key insights into the toxicological effect of the drug or pharmaceutical compound in the early stages of development, meaning that companies can work towards improving the issues or identifying the cause, ensuring that no costly surprises take place during the clinical trials.

Why is it important?

Biopharmaceutical company Gilead Sciences hit the headlines last year after it abandoned a phase III clinical trial of Ambrisentan in patients with Idiopathic Pulmonary Fibrosis (IPF) when it became clear that the treatment was showing no benefits to the patients randomised to receive the drug. As a result of the clinical trial termination, shares in the company fell by two per cent, bring the total yearly fall for 2010 to 16 per cent; a devastating and costly turn of events.

An additional issue could be the discovery of untoward toxicity and other side effects once the pharmaceuticals go to market, with some drugs causing toxicity to the liver, cardiovascular system, skeletal muscles, nervous system and kidneys, however while this type of toxicity is suggestive of a genetic component and not clear until a large number of people have been exposed, attrition at this late stage can be particularly costly and damaging to pharmaceutical firms.

Due to this issue, referred to as mitochondrial toxicity, pharmaceutical firms are investing more in screening methods that would help to identify any potential problems at an early stage, so that drugs can be developed without mitochondrial liabilities and organisations need not go through the expensive task of withdrawing a drug from the marketplace.

"The next hurdle for acceptance of mitochondrial impairment as an important cause of tissue toxicities is to establish tighter linkages between in vitro models and clinical outcomes. Some of this will be accomplished by correlative studies demonstrating relative toxicities for various drug classes in both in vitro and in vivo models, including the clinic," explained James A Dykens, Lisa D Marroquin and Yvonne Will in their report entitled Strategies to reduce late-stage attrition due to mitochondrial toxicity.

The future of predictive toxicology

It is clear that preventing late-stage attrition is of huge importance to all pharmaceutical firms, for both reputational and financial reasons, which is why so many organisations are ploughing time and money into predictive toxicology research. Indeed the Hamner Institutes for Health Sciences, a non-profit research organisation focused on translational safety sciences and a pioneer in liver toxicity research, and PBM Capital Group (PBM) have recently announced a joint venture, the aim of which will be predictive toxicity testing. The organisations will screen drug compounds and hope to create something of an "insurance policy" to find which compounds are toxic to humans, effectively saving pharmaceutical research and development firms billions.

"It is our belief that this research collaboration will lead to innovative science and advances in developing and gaining adoption of the next generation of predictive tools to aid in chemical toxicology and drug discovery and development. We are pleased that the science being developed at our GigaCyte subsidiary can contribute to these advances," said Paul Manning, chief executive officer of PBM Capital Group 

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