BRITAIN: Doctors in north west London treating six young men who became seriously ill after taking part in a drug trial are consulting experts around the world to try to save their lives.
The novel nature of the drug TGN1412, which was being given to people for the first time and which provoked massive inflammation in their tissues and internal organs, means that no one has any direct medical experience to call on.
"The exact sequence of what's happening here is unique," said Ganesh Suntharalingam, clinical director of intensive care at Northwick Park hospital, in Harrow, north west London, where the men are being treated. The men are on organ support machines and receiving steroids to dampen down their immune systems.
The drug TGN1412 was being developed to treat immunological diseases "such as multiple sclerosis, rheumatoid arthritis and certain cancers", said the makers, the German biotech firm TeGenero.
One of the two trial participants injected with a harmless placebo instead of the drug, yesterday gave a graphic account of the distress caused. "The test ward turned into a living hell minutes after we were injected," said Raste Khan (23), a television technician. "The men went down like dominoes. First they began tearing their shirts off complaining of fever, then some screamed out that their heads were going to explode. After that they started fainting, vomiting and writhing around in their beds." Myfanwy Marshall (35), the girlfriend of one of the two men in a critical condition, appealed for international medical help through Ann Alexander, a lawyer, and asked for TeGenero to apologise, and give "full and proper disclosure" on TGN1412.
Ms Alexander said: "Our client's family is sickened by what has happened . . . the scientific and medical community around the world will come forward with suggestions for treatment." She said there was family concern not just about the lack of information but also the "inconsistency" of what was available. "While the doctors are doing everything they can to treat the symptoms they actually don't know what's gone wrong. "I don't feel [ the drugs firm] have issued a proper apology. The words 'I'm sorry' mean an enormous amount to someone who has suffered like this."
Although the investigation by the UK Medicines and Healthcare Products Regulatory Authority could take weeks, scientists believe the new drug itself caused the disaster and that its potential to have such a huge and damaging effect in humans did not show up in the trials carried out on mice and monkeys. Human error was a possibility, but TeGenero's drug was made up and shipped to London by the large German pharmaceutical firm Boehringer Ingelheim.
The human volunteers were given one five-hundredth of the dose that had proved toxic in animals. "That's a very large safety margin," said Roberto Solari, chief executive of the UK's Medical Research Council Technology. He said it was "very unlikely" the volunteers got an overdose 500 times what it should have been. It was more likely, though this was speculative, that the drug had provoked a reaction in humans different to that in animals.
TGN1412 is a humanised monoclonal antibody, a genetically engineered protein that is part mouse but mostly human and which is accepted by the human body. Almost all monoclonal antibody drugs aim to suppress an immune system reaction - but this one does the opposite. "It is designed to turn on white blood cells, particularly a sub-set called regulatory cells," Dr Solari said.
Inflammatory reactions in rheumatoid arthritis are caused by too many cells in the immune system being turned on. Unlike most drugs which try to switch off troublesome white blood cells causing inflammation, this drug tries to turn on other cells that have the power to switch off the trouble makers. It is possible, Dr Solari said, that "instead of switching on the regulators, we have switched on the activators and super-induced the immune system".
Meanwhile, the Department of Foreign Affairs said it had not been asked for consular assistance by the family of Ryan Wilson Flanagan, the London-Irish man who is one of the six being treated. He was reported to be critically ill yesterday. A spokesman said: "We haven't been asked for assistance in the case so we have no information on it."