In the news
6 Sep 2008
13 October 2006
Non-animal drug testing needed to avoid another TGN1412
As a report is published today1 criticising the company making the ‘clinical trial disaster’ drug TGN1412, the UK’s leading non-animal medical research charity, the Dr Hadwen Trust, warns that an urgent switch to non-animal drug testing is needed to eliminate the dangers of misleading animal testing.
The report by two Dutch research experts said UK regulators missed and misinterpreted findings from primate experiments and that species differences between primates and humans was underplayed by the German company TeGenero.
Six human volunteers suffered life-threatening side effects after taking the experimental drug TGN1412 at Northwick Park Hospital in north London in March 2006. The clinical trial was designed to translate test-tube and animal results into human realities.
TGN1412 had been tested on rodents, dogs and monkeys, but the very severe side effects experienced by the volunteers had not been predicted. There were considerable gender and species differences in drug effects even between the two species of monkeys used, making the results impossible to interpret for humans.
Before the human trial, TeGenero claimed that drug-binding sites for TGN1412 in rhesus and cynomolgus monkeys are identical to those in humans. However, other experts had reported differences of up to 4% between rhesus and human binding sites. This means the strength of the drug’s effect could be substantially different in monkeys and humans, and the monkey tests were insufficient to assure safe predictions for humans.
Dr Gill Langley, the Dr Hadwen Trust’s Science Director, says:
“A systemic weakness of current drug development is its reliance on animal tests. Because of species differences, even results from studies on monkeys can fail to predict human outcomes, as happened in this case. Species differences like this, and further disasters like the TGN1412 trials, are almost unavoidable for as long as we persist in depending on animal models, instead of switching our focus to more relevant and reliable non-animal test methods.”
The Dr Hadwen Trust warns that system change is needed to modernise drug testing regimes, improve safety and increase the quality and relevance of the studies. It rejects calls for further animal tests.
Dr Langley says:
“More animal tests are not the answer. There is already an over-reliance on animal studies to assess the safety of new medicines, especially very human-specific medicines, and a chronic lack of investment in developing sophisticated in vitro studies using human cells. The government needs to learn lessons from this episode and swiftly revolutionise our drug-testing methodologies to take advantage of the scientific, as well as ethical, benefits of a modern non-animal system. We should be using sophisticated in vitro human cell-based studies and safe human microdose studies, which allow ultra-low drug doses to be administered to volunteers to assess the amount of drug-binding in humans. This would also provide essential human, rather than animal, data on how long the drug remained in the body and how it is metabolised.”
ENDS
Notes to Editor:
1 Report by Dr Marcel Kenter, Central Committee on Research Involving Human Subjects, The Hague; and Dr Adam Cohen, Centre for Human Drug Research, Leiden. ‘Establishing risk of human experimentation with drugs: lessons from TGN1412’, The Lancet 2006; 368:1387-1391.
