In the news
6 Sep 2008
20 June 2006
Reflections on a drug trial disaster
Six volunteers suffered life-threatening side-effects from a test drug in March 2006, during a clinical trial designed to translate test-tube and animal results into human realities. The drug, called TGN1412, had been tested on rodents, dogs and monkeys but the very severe side effects experienced by the volunteers had not been predicted. The Dr Hadwen Trust for Humane Research, the UK’s leading non-animal medical research charity, warns that we must learn lessons from this disaster and replace animal experiments with more reliable non-animal methods.
TGN1412 was intended to treat diseases such as rheumatoid arthritis, where the immune system attacks the body’s own tissues. It was supposed to activate regulatory immune cells which would then ‘damp down’ the immune system overall. Instead it massively stimulated the men’s immune system, causing organ failure.
Contamination and overdose have been ruled out. The disaster was caused either by an effect that was not predicted by animal tests; and /or by a misinterpretation of the test results.
Rodents, dogs and monkeys had endured experiments to produce the experimental drug. Rats were lethally irradiated to destroy their immune cells, rats and monkeys endured deliberate inflammation of their joints and toxicity tests were conducted on rats, rabbits, and cynomolgus and rhesus monkeys. None of them had revealed any serious side effects.
Dr Gill Langley, the Dr Hadwen Trust’s Science Director, says:
Protein drugs like TGN1412 are particularly difficult to test in other animal species because they are tailored specifically to target human cells. Sometimes such drugs do not even interact with the cells of other animals. The fact that the drug apparently passed tests on monkeys, who are more closely related to humans than rodents, illustrates the problem. Despite some similarities, there are key differences between monkeys and humans in the receptor used by the drug to interact with the immune cells. Species differences like this, and further disasters like the TGN1412 trials, are almost unavoidable for as long as we persist in using animal models instead of switching our focus to more relevant and reliable non-animal test methods.
The U.S. Food and Drug Administration acknowledges that 92% of all experimental drugs that pass animal tests, ultimately fail to be safe and effective in humans. For protein drugs like TGN1412 the failure rate may be higher.
