NewScientist.com news service
April 5, 2006
By 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 humans”, 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.”
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 product”. 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 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.
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.
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.
* One drug trial, six men, disaster…
* 23 March 2006
* Catastrophic immune response may have caused drug trial horror
* 17 March 2006
* New drug trial puts six men in intensive care
* 15 March 2006
* Statement on TGN1412, TeGenero
* Monoclonal antibody, Wikipedia
* Medicines and Healthcare products Regulatory Agency