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The Disasterous Clinical Trial in London: Chapter 2

Some disturbing news relating to the disastrous London phase one clinical trial that left six initially healthy volunteers hospitalized and in critical condition. Last week, TeGenero AG's chief scientific officer, Dr. Thomas Hanke, said healthy participants were used in the trial because TGN1412, the monoclonal antibody being tested, was not thought toxic.

But now we have this from the Times of London:

"Trials last year in America of a similar "monoclonal antibody" caused severe toxic reactions in patients. But the UK study went ahead after the regulatory authority failed to consult outside specialists who would have warned against proceeding.

"Angus Dalgleish, a world expert on immunology, said yesterday that he was amazed the trial had been allowed to proceed. "The previous studies which caused similar severe side effects were in patients already suffering from cancer, but [the researchers] should have known they would get a meltdown because this drug was hitting exactly the same immune response pathways," said Dalgleish, a professor of cancer at St George's hospital medical school, south London....

"The data that should have raised the alarm were presented at a meeting of the American Society of Clinical Oncology last May. Dalgleish said an engineered antibody, developed by a team led by Steven Rosenberg at America's National Cancer Institute, and using the same pathway as TGN1412 had produced severe side effects in about half of a group of patients dying of cancer."

There's also this report from Australia's Daily Telegraph, saying that monkeys on whom the agent was previously tested had suffered swollen lymph nodes. This at least appears to contradict TeGenero's earlier statements about the drug's safety record, as well as statements in the London volunteers' consent documents about the lack of "significant side effects" in animal studies (though one may wonder whether the monkeys' lymph-node swelling was "significant").

Beware these layers of hearsay, but Daily Telegraph also quotes an unnamed German newspaper as reporting that "Clinical Immunology, a US-based journal for the medical research industry" published a study in 2002 "warning of the problems involving human cells being adversely affected by the medication." It's not clear exactly which journal or study is meant. Nor is it clear the extent to which the monkeys' alleged lymph-node swelling or the cellular problems allegedly reported in the 2002 study should have forewarned researchers about the horrific adverse reactions actually experienced by their volunteers.

The trial was being run for TeGenero by Parexel, an American firm. A series of brief statements from TeGenero appear here. Parexel's terse statement about the trial appears on their website, here.
- Stephen Latham