BRIAN DEER:
MONKEY BUSINESS Page
1
The
Sunday Times (London) September 24 2006
TGN1412
victim given drug 'too quickly'
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.
