THE DRUG TRIAL THAT WENT WRONG

The Drug Trial that went Wrong

The Drug Trial that went Wrong

In March 2006, six men were taken seriously ill whilst acting as 'healthy volunteers' in a clinical trial at an independent research facility run by American company Parexel on the site of Northwick Park Hospital, London.  This episode of the documentary series Dispatches (Channel 4, 28th September 2006) tries to uncover what might have caused an apparently routine safety trial to go so dramatically wrong.  As well as discussing the case with a number of experts on clinical trials, investigative journalist Brian Deer spends a lot of time talking with Ryan Wilson, the man most badly affected by the trials.  In keeping with this genre of reporting, there is also the compulsory pursuit of a representative from Parexel, in the vain hope he might talk on camera.

This important story about a drug trial that went wrong in London has almost been buried by the alarm over a single case of H5N1 in a swan in Scotland. In the middle of last month, six people were taken seriously ill--with multiple organ failure--after taking part in a small clinical trial of an antibody treatment called TGN1412.

The mishap was so serious that Britain's Medicines and Healthcare products Regulatory Agency (MHRA), a government body, swiftly launched a full inquiry. On Wednesday of this week it announced interim findings. The trial had been run correctly, doses were given as they were supposed to, and there was no mistake in manufacturing. In other words, there was something unexpected about the drug itself, despite testing on animals and human-cell cultures, and despite the fact the doses given to humans were only 1/500th of what had been given to animals.

This is a difficult result for the drug business because it raises questions about the right way of testing medicines of this kind. TGN1412 is unusual in that it is an antibody. And it is an unusual antibody as well. Unlike all other antibody drugs it is what is called a “superagonistic” antibody, designed to increase the numbers of a type of immune cell known as regulatory T-cells.

Reduced numbers, or impaired function, of regulatory T-cells has been implicated in a number of illnesses, such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis. Boosting the pool of these antibodies seemed like a good treatment strategy. Unfortunately, that strategy fell disastrously to pieces and it will take a little longer to find out why.

The result highlights concerns raised in a paper just published by the Academy of Medical Sciences, a group of experts based in London. It says there are special risks associated with novel antibody therapies. For example, their chemical specificity means that they might not bind to their targets in humans as they do in other species.

The MHRA has decided that a working group of experts is now needed to decide how trials of this sort of drug can be handled more safely. Its main concern is how to test protein molecules that have novel modes of action--particularly ...