Trial and error

A disastrous phase I trial in 2006 raised questions about the safety of drug testing

In March 2006, six healthy volunteers taking part in a phase I drug trial at Northwick Park Hospital, London, were given small doses of a new drug being developed for rheumatoid arthritis. The drug, a monoclonal antibody known as TGN1412, had been through animal testing, and the trial had been approved by the Medicines and Healthcare Products Regulatory Agency (MHRA).

Within an hour of receiving the drug, the first volunteer reported a headache and began to complain that he was ‘burning up’. Within 24 hours all were in intensive care. Although none of the participants died, they all spent at least a month in hospital.

What went wrong? Intensive investigations revealed that the firm responsible for TGN1412, TeGenero (which has since gone bust), followed all appropriate safety regulations and the materials themselves were not contaminated.

The likely explanation is that the drug acted in unexpected ways in the volunteers, triggering a massive immune response. The drug had no such effect in the monkeys it had been tested on previously, even though they have a very similar version of the target molecule.

So, should the trial have been approved? The drug targeted a key component of the immune system. Was it too risky to be trialled in people? Extra safeguards have now been put in place for agents that target the immune system in this way.

The case is a reminder that clinical trials are risky. Mercifully, extreme reactions like this are very rare. It also emphasises why phase I trials are so important. Safety is paramount, and lessons have been learned from the TGN1412 incident. Regulation has been simplified and streamlined in an attempt to collect as much information as possible about risk factors before a clinical trial is authorised.

It is hoped that in the future computers may be able to give us greater information about how a drug might react in the body. This, along with animal models, will hopefully prevent another case like Northwick Park from happening.

Lead image:

  Pollobarba/Flickr CC BY NC ND

About this resource

This resource was first published in ‘Drug Development’ in January 2008 and reviewed and updated in August 2014.

Topics:
Immunology, Medicine
Issue:
Drug Development
Education levels:
16–19, Continuing professional development