Clinical testing under scrutiny after London drug calamity
AFP | March 20, 2006
With the discovery of so many powerful new genetic drugs, testing methods will have to be reviewed following the illness of six human guinea pigs including two in critical condition after a drug trial in London, specialists warn.
"We're pushing the boundaries with very exciting novel biological compounds," Professor Janet Derbyshire told a press conference here.
"We're going to have to think differently about how we evaluate them all the way through, particularly focusing on what information is relevant from the laboratory and the animals," she said.
Animal testing is the stage preceding tests on humans.
The drug involved in the London accident, TGN 1412, has been under development since 2000 for immunological diseases such as multiple sclerosis, rheumatoid arthritis and certain cancers.
Two of the men who fell critically ill after taking part in the trial showed further slight improvement Saturday, the hospital treating them said.
Two of the other four men concerned, who were described as seriously ill, had improved sufficiently Saturday to stop receiving organ support.
The six men had been in good health when they agreed to test a new drug for German company TeGenero AG at a clinical research unit operated by Parexel International, a US drug research company.
But they collapsed in agony, suffering from inflammation, and were rushed to hospital.
The accident in London could not have been avoided using current methods, specialists say.
"There's been a debate already ongoing before this case about a better safety assessment of new drugs," said Professor Derbyshire, who heads the clinial trials unit of the British Medical Research Council.
One method would be to produce laboratory animals genetically modified so as to share genes with humans.
For example, mice could be given human immune systems, specialists say.
A minuscule dose of the drug under trial is another possibility. It would mean isolating the arm of a human guinea pig from the rest of the body, then injecting it with a very small dose. All results, whether good or bad, would be confined to the arm.
German health authorities have responded to the TGN 1412 test gone wrong by deciding that tests of high-risk drugs must in future be carried out on only one human guinea pig at a time and not on several simultaneously.
New drugs could also be tested on patients already suffering from the disease the drugs are intended to alleviate, suggested Kate Law, a doctor with the British group Cancer Research UK, the biggest non-profit-making cancer research organisation outside the United States.
"There are people who have had really three or four cancer treatments already," said Law. "Being offered to face one trial does at least give them some hope and also the knowledge that they're going to maybe help cancer patients in the future."
Some 250 million patients worldwide are already being treated with some 70 drugs synthesising antibodies. Almost all operate by blocking a chemical process or preventing the action of a protein.
One of the best known is Herceptine which neutralises a protein and thus helps to cut practically in half the resurgence of the most aggressive breast cancers.
TGN 1412 produced by the German laboratory TeGenero AG does the opposite. Instead of blocking, it releases a molecule situated on the surface of white corpuscles.
The molecule in turn triggers a chemical reaction that helps corpuscles to identify and destroy certain cells involved in leukemia and multiple sclerosis.
David Glover, formerly a researcher at Cambridge Antibodies Technology (CAT), a private research laboratory, said this was the chain reaction that had occurred in the case of the guinea pigs in London, but with wholly unexpected effects.
Last modified March 20, 2006