Problems in drug trial of a monoclonal antibody therapy

April 14, 2006
Journal Calls for Change in Drug Trials
By THE ASSOCIATED PRESS

Filed at 7:43 p.m. ET

LONDON (AP) -- Britain's leading medical journal called Friday for
''urgent change'' in the processes for approving and regulating human
drug trials involving man-made antibodies, weeks after authorized tests
left six men fighting for their lives.

The six men were hospitalized in Britain with severe side effects after
volunteering to test the TGN1412, a monoclonal antibody, or a
genetically engineered version of an antibody, which defends the immune
system against infections.

If successfully tested, the drug would have been used to fight leukemia
and autoimmune and inflammatory diseases.

Britain's Medicines and Healthcare products Regulatory Agency, or MRHA,
authorized the tests after receiving the results of experiments on
animals and detailed guidelines on how the test would be conducted.

Five of the volunteers, the first humans to test TGN1412, have been
released from the hospital. The sixth is no longer in critical
condition and is improving, said Dr. Ganesh Suntharalingam, clinical
director of intensive care at Northwick Hospital, in London.

The Lancet said that the MRHA's interim findings -- released earlier
this month and saying there was no fault with either the drug or the
testing procedures -- proved changes were needed.

The journal said that the severe reactions in tests on humans, despite
no similar signs in animals, showed that the existing process may be
flawed. Human trials can only take place after successful laboratory
tests on animals.

The drugs makers TeGenero AG, of Wuerzburg, Germany, said the drug
previously had been tested on rabbits and monkeys with no
''drug-related adverse events.''

''The TGN1412 events indicate that urgent change is needed in the
approval processes and regulation of Phase I trials of biological
agents,'' The Lancet's editorial said, referring to first-time tests on
healthy humans of drugs such as monoclonal antibodies. It did not give
examples, however, of what changes could be warranted.

MRHA has set up an independent expert group to investigate the case and
prevent it happening again, an MRHA spokesman said on condition of
anonymity, in line with organization policy. The expert group will
focus solely on the science surrounding monoclonal antibodies, and how
the future development and testing of such drugs can be carried out
safely, he said.

The trial of the monoclonal antibody was being run at a London hospital
by U.S.-based Parexel International.

The MRHA authorizes around 1,100 clinical trials in Britain each year,
350 of which are Phase I.

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