<<< Start <<< | page 1 of 3 | 1 | 2 | 3 |
TeGenero's TGN1412 drug trial

The Sunday Times

Monkey business

TGN1412 victim given drug 'too quickly'

The Sunday Times, September 24 2006

Brian Deer

A “RECKLESS” mistake apparently overlooked by government regulators lay behind the drug trial disaster that saw six young volunteers badly injured by an experimental medicine.

Confidential documents obtained by The Sunday Times and Channel 4’s Dispatches programme reveal the drug was administered on average 15 times more quickly to the volunteers than to monkeys in earlier safety studies.

The possibility that such a crude error led to the disaster is likely to raise questions over whether the government’s Medicines and Healthcare products Regulatory Agency (MHRA) scrutinises trials adequately and protects the public from the risks of new medicines.

After the “Elephant Man” trials at Northwick Park hospital, London, in March, which left two men fighting for their lives and all six in intensive care, the agency said the reactions resulted from an “unexpected biological effect”.

However, experts say the drug, TGN1412 — one of a new generation of “magic bullet” treatments targeting the immune system — was infused so quickly into the volunteers that the potential for life-threatening problems was foreseeable.

“When you give an antibody . . . the quicker you put it in, the more likely you are to get an infusion reaction,” said Professor Terry Hamblin of Southampton University, a leading authority on monoclonal antibodies, the family of drugs to which the trial medicine belonged.

The volunteers were given TGN1412 in only three to six minutes. “To quickly infuse it over three to six minutes in six individuals I think is . . . reckless,” said Hamblin.

Ryan Wilson, 20, a former apprentice plumber, who suffered total organ failure, was the most seriously injured. He was given the drug in just four minutes. The monkeys, by contrast, received the antibody by a one-hour “slow infusion”.

Hamblin’s judgment is backed by other experts, including Dr David Glover, formerly chief medical officer of Cambridge Antibody Technology. He concludes: “The drug was given too quickly.”

The speed at which the monkeys received TGN1412 was set out in the application to the MHRA for permission to carry out the trial. This was submitted by Parexel International, a contract research company, on behalf of TeGenero, a tiny German drug developer. But the paperwork did not explicitly detail how quickly the volunteers would be given the drug, although this could be calculated from the information given.

Professor Kent Woods, the agency’s chief executive, said this weekend the results of the monkey trial had reassured his staff that the human project should be allowed to go ahead. “They did not show toxicity and the dose was 500 times higher on a weight-for-weight basis than that first used at Northwick Park,” said Woods. “That is the key issue.”

There was another apparent oversight in the agency’s scrutiny. Parexel’s paperwork did not include data on test-tube experiments designed to show the drug’s effect on human cells. One specialist said she was “pretty astonished” this was left out, although it is unlikely the data could have predicted the disaster.

This omission was only revealed after an appeal by The Sunday Times and Dispatches under the Freedom of Information Act for the reinstatement of paragraphs cut from documents released by the MHRA.

While the agency suggests in its assessment of the trial that the problems could not have been foreseen, experts say the reactions to TGN1412 — pain, vomiting and organ failure — have long been linked to first doses of monoclonal antibodies, and in previous incidents infusion time has been a critical factor.

Parexel declined to comment, and in Thursday’s Dispatches the company’s chairman, Josef von Rickenbach, takes refuge in a hotel lavatory.

Wilson has severe injuries. He has had his toes and sections of his feet amputated. Parts of his fingers have dropped off; others have died and are hard as wood to the touch where the blood supply was cut off as his body reacted to the drug.

TeGenero's TGN1412 drug trial
| 1 | 2 | 3 | >>> next page >>>

This report is copyright, Brian Deer. No portion of this article on Ryan Wilson and the TGN1412 drug trial may be copied, retransmitted, reposted, duplicated or otherwise used without the express permission of the author. Responses, information and other feedback are appreciated