Initial report clears Parexel
Probe of injuries during tests hints problem was drug
Investigators in Britain have ruled out contamination, overdose, and procedural problems in the case of an experimental biotechnology drug that sent six patients to the intensive care unit of a London hospital last month.
The drug test run by Parexel International Corp. of Waltham is still under investigation by Britain's top medical authority, but an interim report yesterday suggested the problem is more likely to lie with the drug itself, which had never been tested in humans before.
The drug, an antibody designed to fight leukemia, rheumatoid arthritis, and multiple sclerosis, was being tested in a northwest London hospital when all six paid volunteers who received doses had dramatic inflammation reactions and were sent to intensive care. Two had life-threatening organ failure.
One volunteer's head swelled so much he looked like ''the Elephant Man," his girlfriend said at the time, and the story quickly became front-page news in Britain.
Five of the volunteers, who were all men, have been released from the hospital and the sixth has recovered enough to be moved out of critical care, the hospital said yesterday.
The trial has become a widely watched case study in the risks and complexity of modern drug testing. The drug was developed by TeGenero AG, a small German biotechnology company, and manufactured for testing by German pharmaceutical giant Boehringer Ingelheim. The trial was run by Parexel, an international company that runs human drug tests on behalf of drug developers.
Inspectors from Britain's Medicines and Healthcare Products Regulatory Agency visited offices and facilities of all three firms to see whether the drug had become contaminated or mixed with any other agents during processing. They interviewed Parexel's staff and inspected the hospital wing it runs as a for-profit testing center in northwest London.
A spokeswoman for Parexel yesterday said the company is ''very pleased" that the patients appear to be recovering, and is ''happy the results from regulatory inquiry have found no issue with the service we provided."
Since the trial was halted on March 14, some medical ethicists have raised questions about the structure of the test, in which all of the volunteers appear to have been given the drug on the same day. When testing drugs for their safety in humans, doctors often dose one patient at a time.
''If you build a prototype airplane, you don't build six prototypes and have them all take off at once," said Dr. Greg Koski of Massachusetts General Hospital, who formerly headed the federal Office of Human Research Protections.
Parexel spokeswoman Jill Baker said she couldn't comment on the design of the trial, but that it had been approved by health authorities and reviewed by an ethics committee in Britain.
''Clearly, there were no concerns about whether this was an appropriate way to run the trial," she said.
British health inspectors said the patients' sudden reaction may have been an unexpected side effect of the drug. In previous testing on animals no significant side effects were reported.
To prevent similar problems, the British government is setting up a team of specialists to determine how antibodies and other powerful biological molecules should be tested in the future.
Stephen Heuser can be reached at sheuser@globe.com. 
