Drug trial horror “ the official interim report

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Drug trial horror – the official interim report

 

* 18:49 05 April 2006

* NewScientist.com news service

* Gaia Vince

 

A catastrophic drug safety trial which left six healthy volunteers fighting for

their lives was the result of “a powerful pharmacological effect of the

product in humansâ€, the UK government agency charged with investigating the

incident said on Wednesday.

 

The novel drug, called TGN1412, caused multiple organ failure in the six men

injected with it at a Northwick Park Hospital, London, UK, on 13 March.

 

The severe patient reaction in the first human phase I safety trial of the drug

was not due to a dosing error, product contamination or manufacturing problems,

and the trial was conducted properly according to the agreed protocol, the

Medicines and Healthcare products Regulatory Agency (MHRA) said, announcing its

interim findings.

 

The “unprecedented reaction†to the drug was not seen in preclinical test

animals at much higher doses, Kent Woods, chief executive officer of the MHRA

told reporters.

 

The drug, made by German pharmaceutical company TeGenero, was

being tested as a potential treatment for certain autoimmune diseases and

leukaemia.

 

“Even in hindsight, we can see no evidence of any such adverse reactions from

the preclinical studies,†Woods said.

 

The doses given to the humans in the trial were diluted by 500 times – a

substantially lower dose than that given to non-human primates, which didn’t

show ill effects.

 

â€

Immune response

 

He admits that there was “no simple, non-recurring explanation†to what had

gone wrong, but that there was clearly a “substantial difference in the

preclinical and clinical effects of this productâ€.

 

The MHRA does not yet know exactly how the drug caused the horrific reactions.

Further results are pending.

 

There were however, clues that the drug might have caused a super-immune

reaction, in previous studies on the drug’s own mode of action. _

 

Studies uncovered_ http://www.newscientist.com/channel/health/dn8863.html) by

New Scientist in the days following the horrific incident, and experts

contacted by New Scientist suggested that the event may have been connected to

the way _TGN1412 acts on the body’s immune cells_

(http://www.newscientist.com/channel/health/mg18925444.100.html) .

 

To investigate further, the UK government’s department for health has

established a group of international experts to examine the incident and

recommend ways to prevent future disastrous trials.

 

Exceptional events

 

Until this expert group reports interim findings – expected within three

months – all phase I clinical trials involving biological molecules with novel

methods of action, monoclonal antibodies and immunological targets will not be

authorised until assessed and approved by an independent expert, Woods said.

 

“It is important to recognise that the events in the TeGenero trial were

exceptional and we understand relate to a specific pathway and mechanism of

action of this particular product candidate,†commented Aisling Burnand, chief

executive of the UK BioIndustry Association.

 

Five of the six trial patients have now been released from hospital – the

sixth is out of intensive care, although a lawyer representing four of them told

New Scientist that their health problems continue.

 

“They suffer constant headaches and are not allowed in public spaces due to

dizzy spells and the risk of infection,†he said.

 

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* _One drug trial, six men, disaster…_

(http://www.newscientist.com/article.ns?id=mg18925444.100)

* _http://www.newscientist.com/article.ns?id=mg18925444.100_

(http://www.newscientist.com/article.ns?id=mg18925444.100)

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* _Catastrophic immune response may have caused drug trial horror_

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* _http://www.newscientist.com/article.ns?id=dn8863_

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(http://www.newscientist.com/article.ns?id=dn8852)

* _http://www.newscientist.com/article.ns?id=dn8852_

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