New types of pre-clinical study are needed to protect drug-test volunteers from a repeat of the disaster seen at London’s Northwick Park Hospital earlier this month, experts say.
Six healthy men, all under 40, had volunteered to test an experimental leukaemia treatment called TGN1412, at a private research unit in the hospital run by clinical trial company Parexel. But, within hours of receiving their infusions, all six were fighting for their lives, the victims of an unforeseen but violent reaction to the drug – an antibody designed to manipulate the immune system.
The Medicines and Healthcare products Regulatory Agency is still investigating the incident, and one of the men still remained critically ill as PharmaTimesClinical.com went to press. But, already, scientists and industry figures are predicting that a new tier of testing will emerge for the growing number of antibody treatments.
Such drugs have already provided breakthroughs against cancer and arthritis. But, because some emerging treatments have the potential to stoke up the immune system, experts warn that they might in theory provoke violent reactions of the type seen at Northwick Park. And they say that sophisticated tests on human tissue will be needed before the experimental medicines are given to people in the phase one, two and three clinical trials,
Already, one company, Asterand, based in Royston, Hertfordshire, is offering a service that allows new drugs to be tested on live human organs that have been rejected for transplant surgery. Its chief executive, Randal Charlton, predicted that the US Food and Drug Administration and other licensing authorities would “soon require a range of new tests before Phase I trials are allowed to begin.”
“I believe that within the next five years, the testing of drugs on human tissue will be mandatory before trials begin in people,” he said. Mr Charlton said that 18 of the biggest pharmaceutical firms had already held discussions with Asterand regarding its development of “phase-zero” testing – and that some had already used Asterand’s services to test the effects of new antibody treatments on preserved whole human organs.
Other types of preclinical safety test have also been touted in the wake of events at Northwick Park Hospital. Drug testing expert, Dr David Glover, the former medical officer at Cambridge Antibody Technology, told the BBC that one possible method was a technique called micro-testing. This involves creating a blister on a person's arm - which contains cells that a microscopic amount of a drug could be tested on. "This would mean you could look at the effect on cells before trying it on a whole person."
Another way, he suggested, would be to manipulate the immune system of mice so they contained human immune cells - in order to give a better picture of what might happen when the drug was given to humans.
by Michael Day