Posted by psychosage on January 3, 2005, at 6:06:44
http://www.boston.com/business/articles/2004/12/31/test_approved_that_can_tailor_drug_doses/
Test approved that can tailor drug doses
By Diedtra Henderson, Globe Staff | December 31, 2004WASHINGTON -- The Food and Drug Administration has approved the first genetics-based lab test to help physicians personalize their patients' drug doses.
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The approval hastens a move away from a one-size-fits-all drug dose, offering help to patients with wildly varying responses to such popular drugs as antidepressants and antipsychotics.
The AmpliChip Cytochrome P450 genotyping test could reduce toxic side effects experienced by people who process prescription drugs slower than normal. At the same time, the test could personalize doses for hypermetabolizers, who often feel no benefit from standard drug doses.
The test is made by Roche Molecular Systems Inc. An agency official expects that more genetic test kits are on the way as the FDA pushes drug companies to embrace cutting-edge science to improve drug safety.
"If we are smarter about drugs, about how we dose them and how we use them, then we can make drugs both safer and more effective. And we can develop them faster," said Dr. Janet Woodcock, the FDA's acting deputy commissioner for operations.
"Just think what this AmpliChip might mean for drugs coming along," Woodcock said. "You wouldn't be getting people who were getting overdosed and getting tremendous side effects. And you wouldn't [have] people getting underdosed and getting no beneficial effect."
Roche's product looks at variations in two genes that are active in the liver. These genetic subtleties can spell the difference between whether a drug dose has a negligible or too-potent effect.
People who metabolize poorly, for instance, can get an unintended jolt that is 10 times the drug's intended effect, Woodcock said.
The FDA approved one of Roche's two applications, but its test analyzes two genes. The second application is expected to be approved shortly.
The Roche test is used in concert with a microarray -- a chip containing millions of DNA molecules -- built by Affymetrix Inc. The system would effectively question the patient's blood about variations in those genes. The answers given by the patient's DNA would indicate whether they metabolize drugs poorly, extra quickly, or somewhere in between.
Right now, drugs on the market like Strattera, a drug for attention deficit hyperactivity disorder sold by Eli Lilly, have a wide range of starting doses, with suggestions that slow metabolizers be prescribed lower doses.
Woodcock called that hand-tailoring process "laborious." Doctors would start a patient on a low dose, then "they'd creep up. But some people, you'd have to go up very high because they'd be hyper metabolizers," she said.
The FDA slowly has been coaxing drug companies to test new products that would point to how individual genetic differences might be linked to drug effectiveness.
If such tests were available during Dr. Barry Eisenstein's tenure at Eli Lilly, researchers could have answered a perplexing riddle. For an unknown reason, depression lessened for some, but not all people, who took Prozac, compared with a placebo.
By singling those people out through genetic analysis, "you'd know in advance how to apply your drug," said Eisenstein, a Harvard medical professor and former vice president of Lilly's research labs.
Various companies, such as Waltham-based BG Medicine, are nibbling away at answers to the question of how human genetics affects drug effectiveness.
For the past three years, the company, formerly known as Beyond Genomics, has built and perfected a tool kit to compare many indicators in human blood, including cytochrome P450 genes, enzymes, proteins, and small molecules. The measurements are analyzed and converted into a visual display. The goal: predicting which people respond to a given drug, versus those who will not respond.
The next step is working with a pharmaceutical company to apply that knowledge to drug development.
Stephen Martin, BG Medicine senior vice president, said the technology is likely to be introduced in early clinical trials to ensure experimental drugs are tested in people most likely to respond.
"There are so many opportunities out there," Martin said. The company is talking to several pharmaceutical groups "to really choose a coup
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