Two Men Remain in Coma From British Drugs

Associated Press | March 21, 2006
By TARIQ PANJA

They were chosen because they were fit and healthy, but minutes after being injected with a test drug designed to combat leukemia and other diseases, the men went into convulsions as their internal organs began to fail.

Two men were still in a coma Tuesday and four others were seriously ill but improving after participating in the trial last week. The drug sent the men into vomiting fits; they removed their shirts in panic as their bodies seized up with pain.

Fresh questions are being asked about the safety of clinical trials and whether the tests draw vulnerable people with promises of pay. Parexel, one of the makers of the drug, paid eight men 2,330 pounds (US$4,092) each to participate, said Raste Khan, 23, one of two patients who had been given a placebo.

He described the gruesome scene in the hospital ward.

"It felt like we stepped into some sort of horror film," Khan told The Associated Press. "The three other men in my ward started vomiting, then they began to fall in and out of consciousness. The person on my left was begging doctors to help him. I was really scared and was just waiting for it to start happening to me."

After taking the drug the men lapsed into comas as their organs failed, forcing doctors to put them on organ support machines, said Dr. Ganesh Suntharalingam, who was treating the men at Northwick Park hospital in London.

The Medicines and Healthcare products Regulatory Agency _ which authorized the trial _ said there was nothing unusual about the results of laboratory and animal tests on the drug or the methodology for the human trials provided by Waltham, Massachusetts-based Parexel and the other maker, TeGenero AG of Wuerzburg, Germany.

TeGenero's chief scientific officer, Thomas Hanke, said the drug TGN1412 _ designed for the treatment of autoimmune and inflammatory diseases and leukemia _ had been tested on rabbits and monkeys with no "drug-related adverse events."

MHRA spokeswoman Sara Coakley said the reaction of the six study participants was "completely unheard of."

"There could have been a manufacturing problem, some form of contamination, a problem with the drug's administration, or ... it could be that (defects with the drug) just didn't show up in preclinical data from the tests on primates," she said. "It will be weeks before we find out exactly what happened."

Some experts, however, said the six men should not have received doses within such a short period.

"The idea you give six people an injection at the same time is unusual," said Kate Law, head of clinical trials for Cancer Research U.K. _ Britain's largest cancer charity. "In any of our tests we never test drugs on the volunteers all at the same time."

David Glover, former chief medical officer at biotech company Cambridge Antibody Technology, said testing antibody drugs like TGN1412 must go on despite the tragedy. He cited drugs like Herceptin, which has made a big impact on the treatment of breast cancer.

"We need to understand the issues we face and look at creative solutions," said Glover.

Most phase one trials _ in which the drug is tested on humans for the first time _ are conducted in industrialized nations. In Britain, the MHRA authorizes around 350 such tests per year.

Complicated health regulations and the need for sophisticated infrastructure usually prevent such trials from being conducted in developing nations. Phase two and three trials, in which the drug is tested on patients in need of treatment, can take place in poor countries.

The procedure for selecting healthy volunteers for phase one trials has also caused controversy in Britain in the aftermath of the men's hospitalization.

Parexel recruited the eight men for what should have been a two week trial, said Khan. They were to stay for three nights, and then attend 11 follow up days.

"It worries me that you could earn a living from being a participant," said Ray Noble a medical ethicist at University College London. "It might blind people to the obvious potential pitfalls of participating in too many trials."

Others say that without offering financial inducements it would be extremely difficult to get subjects for the essential phase one tests.

"It's a fine line. How do we attract people to do something for which there is not much reward?" said Derbyshire.

Last modified March 21, 2006