Experts release interim report on UK clinical trials

Clinical trials of new drugs need to be tightened up, according to an expert group convened in the aftermath of trials that left six people fighting for their lives.

But the group’s interim report is seriously flawed, according to a leading consultant to the pharmaceutical industry, because it fails to criticise the regulatory body that approved the clinical trial of TGN1412.

TGN1412 is a monoclonal antibody, developed by German biotech firm TeGenero, designed to stimulate the body’s immune response by binding to CD28 receptors on the surface of immune cells called T cells. The drug was intended to help combat diseases that alter the immune system, such as leukemia.

But six healthy volunteers who took the drug suffered fever, extreme swelling and, in several cases, organ failure.

An earlier investigation by the body that approved the trial, the Medicines and Healthcare products Regulatory Authority (MHRA), concluded that the disaster was a side effect of the drug that could not have been predicted. The government subsequently commissioned an expert group, led by Gordon Duff, professor of molecular medicine at the University of Sheffield, UK, to investigate risks associated with related drugs and review the clinical trials procedure.

Expect the unexpected

The interim report, released on 25 July, makes general suggestions of ways to make clinical trials safer that have been welcomed by stakeholders such as the Association of the British Pharmaceutical Industry and the BioIndustry Association.

But not everyone is impressed.’I had hoped the Duff report would overturn the MHRA’s conclusion that the side effects were unexpected,’ said David Glover, an independent consultant and former chief medical officer at Cambridge Antibody Technology, UK. ’They should have been expected, and things could have been done,’ Glover told Chemistry World.

The drug was being developed for immunosuppressed patients, and Glover argues it was a mistake to test it on people with healthy immune systems. ’The idea is to kickstart the immune system’ he said, ’but in a healthy person, it doesn’t want kickstarting’.

Glover, who worked at Cambridge Antibody Technology when it was developing an agonist monoclonal antibody called ETR1 with US firm Human Genome Sciences (HGS), says ETR1 went through considerably more intense scrutiny with the US Food and Drug Administration before entering clinical trials in patients, rather than healthy volunteers. HGS has now completed three Phase II trials of ETR1 in cancer patients.

Sensible suggestions

The group has at least made some sensible suggestions for the future, said Glover. Duff’s expert group has recommended the setting up of relevant expert advisory groups for new classes of drug, for example. ’Avoidance of a similar occurrence in the future will depend on regulators seeking the correct expert opinion and working to ensure a more cautious approach in trial design,’ agreed Neil Williams, an immunologist at the University of Bristol, UK. The Duff group also suggested that information from trials should be shared much more freely, even if they were unsuccessful.

However, the expert group focussed on scientific issues arising from the TGN1412 trial, rather than the trial itself, so an investigation is still urgently needed, adds Glover.

That wasn’t the purpose of the report, said a spokesperson for the Department of Health, which issued the report. ’The purpose wasn’t to say "this was wrong, that wasn’t wrong",’ she said. ’It is about learning lessons.’

Bea Perks