Drug firm 'had not tested on humans before'

The German company whose drug trial has left six men fighting for their lives after it went badly wrong had never tested its products on humans before.

Thomas Hanke, the chief scientific officer of TeGenero, based in Wurzburg, said the company was "devastated" by the news. The new medicine, known as TGN 1412, had shown no safety problems in laboratory trials or animal tests, he said.

But it emerged yesterday that the American testing company Parexel, which TeGenero had commissioned to run the trial, had initially been refused permission to test the drug in Germany. The Paul Ehrlich Institute in Germany, which was responsible for overseeing the company's proposed drug-testing programme, sent back its project with a lengthy list of deficiencies which it demanded be corrected before testing was allowed.

German media reports said yesterday that Parexel was eventually granted permission to carry out the tests in Germany after the deficiencies had been ironed out, but by then the company had approached the British medical authorities for permission to carry out tests in the UK.

Lawyers acting for one of the victims at Northwick Park hospital, north-west London, raised doubts about the animal experiments that TeGenero claimed to have carried out. Ann Alexander, of the solicitors' firm Alexander Harris, whose 29-year-old client is on life support, said: "There is confusion about whether the drug had been tested successfully and safely on animals before the tests on these volunteers."

In one meeting with the families of those involved in the trial, company representatives said the drug had been tested on monkeys and dogs and one of the dogs had died, she said. In a second meeting, they were told tests had been carried out on monkeys and rabbits and the company had denied testing the drug on dogs. "It has been a devastating tragedy and these mixed messages cause great concern," she said.

Yesterday, Mr Hanke said that the drug had been tested on monkeys and rabbits and that no animals had died.

Four of the men were improving in Northwick Park hospital, but two were still critical, the hospital said in a statement. The six men were rushed to the intensive care unit on Monday after suffering a severe reaction and multiple organ failure within hours of taking the drug, a monoclonal antibody designed to combat inflammatory reactions in leukaemia, multiple sclerosis and rheumatoid arthritis. Instead, the drug triggered an overwhelming inflammatory reaction in the six human guinea pigs. Two further men who took a placebo were unaffected.

Scientists said the men may have been given too high a dose of the new drug. Professor John Henry, a clinical toxicologist at St Mary's Hospital, London, said: "The dose they were using is the whole key here. What was their target dose and what did they start with? They should have started with a minuscule dose and given it to the first two volunteers to see if there was any reaction. Then they should have moved on to the next two volunteers and multiplied the dose. You can't, in all conscience, give six people the same dose and hope they will all react perfectly."

Professor Henry, a former consultant physician in the National Poisons Unit at Guy's hospital, said: "It is just common sense. If that is not part of the legal requirement for Phase 1 safety trials then it should be."

The US-based medical testing company Parexel, which has a 36-bed unit on the Northwick Park hospital campus, said in a statement: "Parexel administered the appropriate dosage to the volunteers based on the protocols designed by the sponsor, TeGenero, and which were approved by the ethics committee and the regulatory authority."

The head of a testing company in the Midlands, who asked not to be named, said he and his colleagues were praying the tragedy was the result of human error. "If it is not due to human error then it means that you can take a new molecule through discovery and laboratory testing, through all the animal studies and see nothing untoward until you take it into man at a minuscule dose and you see a catastrophic event. That would undermine the testing and development of all new medicines."

Patients saw TV reports of their imminent death

The six men rushed into intensive care after being injected with TGN1412 were warned they could die within hours by news headlines flashing on televisions in their ward, a patient's relative said.

As the men slipped in and out of consciousness, suffering severe reactions that led to swelling, vomiting and pain so extreme that one patient begged doctors to sedate him, they heard hospital statements warning of their potential fate.

The relative, whose son is in a serious condition at Northwick Park Hospital in north-west London, said: "There are six patients in there with TVs in their rooms and my relative, who was just starting to communicate, was there, in bed, watching the hospital press statement which said he could die in a matter of hours. I was so angry. Everyone was distraught."

The relative said that the hospital statement left "friends and families panicking". He said: "One minute he was being told that in two days he would be better. But on the outside they are saying there is little hope. I can't imagine what those patients were thinking as he heard that. I was furious."

One of the two men in a critically ill condition was named as Ryan Wilson, 21, a student, of Highbury, north London.

The name of the other critically ill patient, who is 28, has not been disclosed. His partner, Myfanwy Marshall, who said his head had swollen up to look like the "Elephant Man", made a plea for help with his treatment. The patient's solicitor, Ann Alexander, said: "She wishes that there should be the widest possible attention to this tragedy in the hope that members of the scientific and medical community around the world will come forward with suggestions for treatment."

One of the eight volunteers, Raste Khan, 23, who was given a placebo, said: "It was like Russian roulette - two of us got away and were lucky."