ANIMAL tests of new biological drugs such as the one that caused the disaster at Northwick Park need to be scrutinised much more carefully by scientists and regulators, scientists said yesterday.

The news came as eleven patients from nine countries died in a separate trial for an Alzheimer’s drug.

David Glover, for ten years chief medical officer at Cambridge Antibody Technology, said that animal tests could foster a false sense of security and might have done so in this case. There were two reasons.

The first was that humanised antibodies such as the drug TGN1412 were perceived as foreign when injected into animals and were therefore rejected by the animal’s immune system before they could exert their full effect. The second was that monoclonal antibodies (MABs) such as TGN1412 were exquisitely specific, directed at a single human protein, to which they attached themselves. “In animals binding may not occur because the antibody may not recognise any animal tissue at all, or binding may be weaker,” Dr Glover said.

This meant that in animals it is easy to generate data showing no negative effects, and to proceed into human experiments believing the drug to be safe. “That would be my concern in this case,” he said. “Everybody followed the guidelines, came up with nothing, and assumed it was safe to go into Man. That applies to the company, and to the regulators, and to the people who conducted the trial.”

MABs fall into two distinct classes: those that act to neutralise, or block, a human protein (the cancer drug Herceptin is an example); and those that, like TGN1412, have positive effects, stimulating a process or starting a cascade of activity. These are called agonist antibodies: TGN1412 was designed to stimulate the killer T cells of the immune system.

The blocking type was intrinsically safer, Dr Glover said, because if things went wrong the antidote was, theoretically, to add more of the protein being blocked. But there was no antidote if the drug triggered a cascade of activity, as appeared to have happened in this case.

He also questioned whether the decision to test TGN1412 in healthy human volunteers had been the right one. The alternative was to go straight into patients, where the balance of risk and benefit was different. At Cambridge Antibody Technology he had organised trials for five MABs — two had been tested in healthy volunteers, three in patients. MABs are the fastest-growing sector of the pharmaceutical industry, with a market expected to be worth close to £20 billion by the end of the decade.

There have been earlier hiccups. One trial of an MAB designed to prevent organ rejection was stopped when patients were found to be at much greater risk of contracting serious infections. But these kinds of incidents happen with the older chemical drugs as well.

Japan’s Eisai pharmaceutical company confirmed yesterday that eleven patients from nine countries had died while taking its Alzheimer’s drug Aricept during a clinical trial.

The patients, who all had vascular dementia and a history of stroke or heart disease, were among 648 who had received Aricept once daily for 24 weeks, Eisai said.

Aricept is already approved to treat mild to moderate Alzheimer’s disease. It is used to treat vascular dementia, the second most common form of dementia after Alzheimer’s, in a small number of countries.

Eisai said the incidence of death was similar to that in previous trials.

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