Tony Moffat: genetic tests mandatory |
Regulatory agencies are a whisker away from including genetic
testing requirements in marketing authorisations for new drugs, according
to
Tony Moffat, chief scientist at the Royal Pharmaceutical Society.
Professor Moffat predicted that for certain drugs genetic tests would
be made mandatory before the drug could be prescribed. He illustrated
his point with the example of Strattera (atomoxetine), a new drug licensed
for the treatment of attention deficit hyperactivity disorder.
The drug is primarily cleared by CYP2D6 cytochrome P450 enzymes and,
in clinical trials, patients who were poor metabolisers suffered more
adverse drug reactions than those who were extensive metabolisers. When
considering the application for marketing approval of Strattera, the
US Food and Drug Administration suggested that genetic tests should be
conducted before use.
“That was ground-breaking,” said Professor Moffat. The FDA could
not go further than this because there were no FDA-approved tests. Had
there been an approved test, Professor Moffat believes that genetic testing
would have formed an integral part of the drug’s licence.
“We are now at the brink — the FDA has said you should test,
but they are only a gnat’s whisker away from saying you must test.”
Professor Moffat went on to say that the FDA also wants to improve the
risk benefit ratios of four other drugs — azathioprine, mercaptopurine,
warfarin and irinotecan — by including pharmacogenetic information
in their marketing authorisations. “The FDA is asking companies
for information about pharmacogenetic testing of individuals and the
adverse drug reactions that those patients experienced so it can consider
whether to change the marketing authorisation of the drugs. That is going
on now,” he said.
In the case of mercaptopurine, Professor Moffat explained that the degree
of bone marrow toxicity seen in a particular patient was dependent on
their genetic profile. Those with a limited capability for metabolising
mercaptopurine needed a lower dose than extensive metabolisers. One in
300 patients would need just 10 to 20 per cent of the normal dose if
they were to avoid bone marrow toxicity. “The FDA is revising the
[marketing authorisation] now. Tests are available and I think they will
make it mandatory to test patients before these drugs are given,” he
said. |
The
Pharmaceutical Journal