Sickening 'storms' in drug trials

Six men, including a New Zealander, who became seriously ill while testing an experimental drug had an immune system overreaction known as a cytokine storm, the doctors who cared for them say.

All six men have recovered and the incident appears to have been an unforeseeable consequence of taking the drug, designed to treat chronic inflammatory conditions and leukaemia, said Dr Ganesh Suntharalingam and colleagues at Northwick Park Hospital in northwest London.

Their case can help doctors understand what happens when the immune system overreacts in such a way - which may well happen in future clinical trials, the doctors wrote in the New England Journal of Medicine.

New Zealander David Oakley spoke about the catastrophic trial 10 days ago. His head swelled to Elephant Man proportions and although he made a partial recovery, he is now battling cancer.

The men became ill shortly after they were given infusions of a protein engineered to affect immune system cells.

They were paid volunteers in a study being run by US drug research company Parexel International on behalf of TeGenero, which has since filed for insolvency.

Eight men took part in the trial. Six got the drug and two got a dummy infusion.

Within 90 minutes, the six men who got the drug reported headaches, shivers, nausea, diarrhoea and lower back pain.

When one patient became so ill he had to be put on a ventilator, the doctors decided to put the other five into intensive care just in case. Their blood pressures all plunged and their organs began to fail.

The doctors described a dramatic two weeks during which the previously healthy men developed symptoms that looked like a serious infection known as sepsis, with difficulty breathing.

The doctors struggled to keep the men going as they tried to figure out what had gone wrong. It took weeks to stabilise the patients and to lead them to slow recovery.

Tests of their blood shows they had a cytokine storm - a sudden over-release of immune system inflammatory chemicals.

The over-response of the immune system can kill, and has been described in patients with bird flu.

The researchers found no manufacturing errors or contamination in the drug.

New England Journal of Medicine editor Dr Jeffrey M. Drazen added in a commentary: "As long as we continue to manipulate biology in new ways, we probably cannot prevent all such events from occurring. We must do what we can to minimise risk, but the future health of the world population demands that we not let adverse events put an end to medical progress."

Journal editor DrParexel has not accepted any liability, although a $30,000 interim payment has been made to each of the six men by its insurers. The six victims are reportedly seeking damages of $15 million each.

- REUTERS