BRIAN DEER:
MONKEY BUSINESS Page
2
He is the
worst afflicted of the victims from the tests on
March 13, but all suffered life-threatening injuries.
For development of new medicines, it was the worst
calamity since the 1960s Thalidomide disaster.
In the space
of one hour, Wilson and five other healthy young men,
aged from 19 to 34, were all infused with the drug
through tubes. All were soon in agony. Their blood
pressure collapsed. Their hearts raced. They
struggled to breathe. Their bodies and heads swelled
to grotesque proportions and Myfanwy Marshall, the
girlfriend of one victim, Mohamed Abdalla, 28,
described him as looking like “the Elephant
Man”.
“It
started off with a lower back pain,” Wilson
recalls. “I just remember it getting worse and
worse, and then I remember vomiting, and then just
too much pain and I just blacked out. And that was
it. Gone.”
Wilson’s
deterioration is shown in the documents obtained by
The Sunday Times. They include adverse event forms
filled in at Wilson’s bedside: “09.38
feeling cold”, “09.40 headache”,
“10.00 lower back pain”, “10.10 nausea
and vomiting”, “10.16 pressure on
chest”, “10.22 vomiting (two
episodes)”, “10.40 breathing
difficulty”, “10.50 diarrhoea”,
“11.40 vomiting”, “12.48 pyrexia”
(fever).
“Between
7.30 and 7.40 in the evening, the phone went,”
said Wilson’s mother, Marion Flanagan.
“Somebody said, ‘Your son took part in a
drug trial today.’ I just knew. It might be a
mother’s sixth sense but the hairs on the back
of my neck stood up and, before he could say another
word, I was screaming down the phone at him, ‘Is
my son all right?’”
At 9.30pm
Wilson was admitted to intensive care, vital organs
all supported by machines. For 16 days he was on a
ventilator and in hospital until the end of June.
“It’s like I took a bungee jump into
hell,” Wilson said. “All of them thought
I’d die.”
The TGN1412
trials had been vital for TeGenero, based in
Würzburg, near Frankfurt. The firm had no other
products and its fortunes depended on this drug. It
was being tested in Britain because in 2001, in
response to lobbying, Tony Blair backed moves to
encourage foreign drug trials and attract “big
pharma” investment.
The MHRA is
regarded as Europe’s most business-friendly
regulator. It gave TeGenero the green light on
January 27, just six weeks before the trial began.
Its target, announced last year, is to approve
projects in just 14 days.
TeGenero’s
plan was for TGN1412 to boost part of the immune
system, and so be useful in Aids or radiation therapy
for cancer. If this did not work, plan B was for it
to damp down a different part and so be good for
rheumatoid arthritis or leukaemia.
Professor
Jürgen Drews, former chairman of TeGenero, said the
trial was “the right thing to do”.
A legally
required dossier submitted to the MHRA describes the
firm’s tests on monkeys. Ten cynomolgus macaques
were infused with 50mg of TGN1412 per kilo of body
weight, and another six with one-tenth of this. Their
blood levels were then measured for six cytokines, a
kind of protein. Some levels remained unaltered,
while others rose noticeably. These included IL-6, a
key inflammatory protein.
“The
results weren’t dramatic,” said a senior
immunologist who knows Dr Thomas Hünig,
TeGenero’s chief scientist. “They showed
some kind of effect but it didn’t forewarn in
any way of what followed.”
What followed
was the disaster: a “cytokine storm” in the
human volunteers. In the monkeys, the IL-6 was
measured at 390. In Wilson it touched 5,000.
The MHRA was
baffled. “The adverse incidents did not involve
errors in the manufacture of TGN1412 or in its
formulation, dilution or administration to trial
participants,” was its verdict. “An
unpredicted biological action of the drug in humans
is the most likely cause.”
Documents,
however, suggest the reactions might have been
foreseeable. They do not set out clearly the speed at
which the drug was to be administered but this came
to light when Hamblin performed calculations based on
papers submitted to the agency and later released
under the Freedom of Information Act. His
calculations have since been confirmed in a
confidential Parexel document.
Experts
believe MHRA assessors could have spotted the
difference if they had taken more time to scrutinise
the project.
“I
usually give it over about six hours,” said
Hamblin. “If you give it in less than an hour
you get horrific reactions.”
The MHRA
denies it missed warning signs. “There was no
reason to believe that the administration rate
proposed for TGN1412 would present as a foreseeable
hazard to the subjects,” it stated.
The case has
highlighted concerns over biotechnology.
“Clinical trials in general have an excellent
safety record,” said Professor Gordon Duff, head
of molecular medicine at Sheffield University, who
chairs a government inquiry into the Northwick Park
incident. “But in light of the TGN1412 incident
there is a need to look at future safety of clinical
trials with novel and potentially higher-risk
drugs.”
Some observers
are worried that, if the MHRA gave the go-ahead in
the absence of important information, there may be
room for future mistakes. “It’s a wake-up
call,” said Glover. “We need to redouble
efforts to ensure we don’t have the same
disaster in the future.”
Brian Deer
investigates the TGN1412 incident in Dispatches,
Channel 4, Thursday at 9pm.
