Mar 15, 2006
Critical Trials TGN1412
The BBC reports today that six men are on the critical list after becoming seriously ill while taking part in a clinical trial of a new drug for treating leukemia and arthritis: BBC Report.
The previously healthy young men were being paid (up to £150, $330 a day) to take part in the early stages of a trial of the novel drug TGN1412. However, within hours of their first injection, they reacted adversely (suffering multiple organ failure) and were put in intensive care. The two men receiving placebo in the trial are fine.
The compound in question is biopharmaceutical company TeGenero’s humanized CD28-SuperMAB (TGN1412) which is in trials for rheumatoid arthritis and B-CLL (B-cell chronic lymphocytic leukemia). Following standard toxicity studies it was entered into initial clinical trials. “The drug was developed in accordance with all regulatory and clinical guidelines and standards,” explained Dr Thomas Hanke, Chief Scientific Officer of TeGenero AG, in a statement, “In pre-clinical studies, TGN1412 has been shown to be safe and the reactions which occurred in these volunteers were completely unexpected.”
Adverse reactions to drugs in clinical trials are exceedingly rare, but then TGN1412 is not your everyday small molecule type drug. TeGenero developed this drug, a superagonistic monoclonal antibody, with the aim of balancing T cell (a type of white blood cell) activation by triggering receptors on another group of white blood cells known as T lymphocytes. Today’s events are likely to provide animal rights activists with new fodder to push for animal testing to be banned, they will undoubtedly cite this unforeseen problem as further evidence that animal tests cannot show how a drug might act in people.
Ganesh Suntharalingam of Northwick Park Hospital told the BBC that, “The drug, which is untested and therefore unused by doctors, has caused an inflammatory response which affects some organs of the body.” Why this should be so is unclear. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has withdrawn authorisation for the trial (obviously) and doctors in other countries have been sent a warning not test it.
Sciencebase will keep you posted on events as we hear them, in particular we’ll try to bring you the results of the ongoing investigation as soon as we can. It may emerge that a clinical error is to blame rather than there being a biological problem with the drug itself, we will have to wait and see.
This very unfortunate incident comes just one day after widely acclaimed findings were revealed showing how the totally unrelated statins could reverse atherosclerosis. Such positive results that inspire public confidence in the pharmaceutical industry are almost as rare as the present negative result!
Richard Ley of the Association of the British Pharmaceutical Industry was reported as saying “This is an absolutely exceptional occurrence.” and “cannot remember anything comparable.”
"Deceived Wisdom: Why What You Thought Was Right Is Wrong" from David Bradley. Available now on 
In totally unrelated clinical news. Daily biotech industry newsletter FierceBiotech reports that eleven people have died in a clinical trial of Eisai’s Alzheimer’s therapy Aricept. There were no deaths in the control group, although Eisai says that it is not unusual for a few deaths in any Alzheimer’s trial.
Lord Robert Winston, professor of fertility research at Imperial College London and vice-chairman of the Parliamentary Office for Science and Technology, told BBC Radio 4′s “The World Tonight” that the UK’s clinical trial system has “lots of safeguards” and echoed my earlier thought concerning animal experiments.
“I wonder really whether in fact there’s increasing reluctance to do the preliminary trials on animals because of the difficulties generally in doing animal research,” he told the program, “”That I think is a disaster for humans.”
That said, the current debacle with six men critically ill, four of whom are recovering slowly, occurred despite successful toxicity testing. The ongoing investigation of events is yet to discover whether there was a drug administering error, a toxic contaminant, or whether this really was simply a devastating but unexpected adverse drug reaction (ADR).
In typical sensationalist tabloid style, the UK’s Sun newspaper has been flaunting the interview it did with one of the “placebo” members of the TGN1412. Even the BBC aired the interview. In it, volunteer Raste Khan (who let’s remind ourselves was allegedly being paid £150 a day to take part in the trial) described the ordeal as being like playing Russian Roulette. I’m pretty sure it was indeed an ordeal, but without wishing to sound like an apologist for the pharma industry, the media is once again making a huge deal out of this isolated incident while dozens, if not hundreds of trials countless other drugs are carrying on elsewhere with no such incidents.
It seems like an increasingly suspicious coincidence that these adverse reactions occurred the day after the positive announcements regarding the statins and their potential for reversing atherosclerosis. It’s almost as if…
…I shan’t say.
Quite a timely article in The Onion:
“The Food and Drug Administration today approved the sale of the drug PharmAmorin, a prescription tablet developed by Pfizer to treat chronic distrust of large prescription-drug manufacturers.
Pfizer executives characterized the FDA’s approval as a “godsend” for sufferers of independent-thinking-related mental-health disorders.”
The BBC today reports that the US drugs company, Parexel, which was running the TGN1412 clinical trial has apologised to the families of two critically ill men and four others.
The six are still in intensive care with no word of a reason for the adverse drug reactio they have experienced, which was characterised by feelings of fever, swelling, and problems with most organs
One of the trial participants has been named as student Ryan Wilson, 21, of Highbury, North London and another has been confirmed as a New Zealander.