An investigation into a clinical drug trial which left six men seriously ill in Britain has found no evidence to suggest there was anything wrong with the drug or the way the tests were run, a regulatory body said on Wednesday.
In an interim report, the Medicines Healthcare products Regulatory Agency (MHRA) said the problem appeared to be due to an unprecedented biological reaction to the drug in humans which had not been seen previously on tests in animals.
“Our main conclusion is that there was a powerful pharmacological action of this drug in man which was not detectable in the pre-clinical studies done in the non-human primate species, even in far-higher doses,” MHRA Chief Executive Professor Kent Woods told a press conference.
The drug had previously been tested on rabbits and monkeys.
As a consequence, the MHRA will not authorize any trials for similar drugs without taking external, expert advice.
“This does not mean a standstill on such research but we feel that we need additional expert advice in certain areas relating to the authorization of those studies,” Woods said.
Secretary of Health Patricia Hewitt also agreed to set up a group of international experts to examine the issue further.
Six men were left seriously ill at a hospital in north London on March 13 after taking part in the clinical study to test the drug, TGN 1412, which was designed to treat chronic inflammatory conditions and leukemia.
Of the six, five have left hospital and one is making a good recovery. In the days after the trial, two of the men were described as critically ill with organ failure.
The trial was run by U.S. drug research company Parexel International Corp. on behalf of a German company TeGenero AG.
At the time, Parexel said they had operated within regulatory guidelines and TeGenero said the response did not reflect the results obtained from initial laboratory studies.
Learn lessons
TGN 1412 belongs to a class of drugs known as monoclonal antibodies, which specifically bind to target molecules. TGN 1412 targets and activates an immune system protein called CD28.
“This is a complex scientific issue which raises important scientific and medical questions about the potential risks associated with this type of drug and how to make the transition from pre-clinical testing to trials in humans,” the report said.
MHRA will now seek expert, external advice for any future phase one or first-on-man trials involving monoclonal antibodies or other novel molecules targeting the immune system.
Woods said it was vital that they learnt lessons from the trial in Britain, which he described as a “wholly exceptional occurrence.”
David Webb, professor of clinical pharmacology at Edinburgh University, said the report’s findings could result in a change to the design of first phase trials for monoclonal antibodies.
“One obvious difference might be to dose subjects sequentially rather than at the same time, which at the very least would minimize the number of subjects put at risk,” he said in a statement.