Healthy Skepticism Library item: 1471

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Publication type: news

Mathews A.
FDA Issues Rules on New Era Of 'Personalized Medicine'
The Wall Street Journal 2003 Nov 3

Full text:

In its first major regulatory step in an important new area, the Food and Drug Administration Monday issued draft guidelines outlining when drug companies must submit information on how medicines affect people differently depending on their genetic makeup.

The move will help lay the groundwork for an approach that could eventually transform how drugs are developed and prescribed. Researchers are increasingly finding ties between people’s genes and their responses to certain medications. The field, called pharmacogenomics, ultimately holds the promise of “personalized medicine,” in which doctors would tailor drug regimens to patients’ individual genetic signatures.

“It gives us the possibility of only treating the people who stand to benefit, and weeding out the people who could have serious reactions,” says Janet Woodcock, a top FDA official overseeing the initiative. The goal of the guidelines will be to “provide clarity and facilitate the use of these tests in drug development,” she adds.

Genetic tests are already being used to guide some drug treatments. Doctors can give a genetic test to breast cancer patients, for example, to determine if they should receive the Genentech Inc. medicine Herceptin. Researchers have found genetic markers that could signal which therapy might best treat a patient’s irregular heart beat. Genetic characteristics also can determine how people metabolize certain drugs, which can indicate how well certain medicines — codeine, for one — will work for them.

Furthermore, the FDA already has begun approving new drugs with labeling that includes genetic test information. Strattera, an Eli Lilly & Co. treatment for attention deficit disorder approved last November, says on its label that a genetic test is available that can help show whether patients are likely to metabolize the drug more slowly, which may cause them to experience its effects a bit more strongly. Such patients may have a slightly higher risk of side effects, including reduced appetite.

“We’re moving from a one-size-fits-all paradigm to a targeted paradigm,” says Mitch Martin, a research leader at Roche Holdings AG’s pharmaceutical unit. For the majority of the drugs it is developing, Roche has concurrent programs designed to find genetic or other markers that might help tailor use of the medicine to individual patients.

Roche also has a large diagnostic test business, which is developing products that could be used broadly in pharmacogenonomic testing. The FDA is beginning to provide guidelines for genetic test makers as well and last week told Roche Diagnostics that its new test that scans for genetic variations in how patients metabolize some drugs will need FDA review even before a partial rollout the company had planned, according to a Roche spokeswoman. She said the company believes the test can be made available on a limited basis for research without FDA review.

Drug companies that don’t have big diagnostic testing businesses are concerned that genetic testing could upset the business models behind many of their most successful products. Even as the drug companies have begun to experiment with pharmacogenomics, they fear that the FDA could use the data they gather to limit the target patient population for potential blockbuster drugs.

On the other hand, by identifying narrower target groups that react well to a drug, genetic tests could salvage more limited uses for medicines that don’t appear to be effective among the general population.

The guidelines, which will be finalized after public comment, will specify when the FDA will require drug companies to submit the results of genetic testing performed as part of their clinical trials of new products. To soothe drug companies’ concerns, the agency also will spell out limits on how it will use such data. For one thing, if a company voluntarily submits pharmacogenomic research information that isn’t required as part of a new drug application, the FDA says it won’t use the data in deciding whether to approve the drug. The FDA also says it won’t move abruptly to add genetic tests to its list of requirements for research trials of new drugs.

Major drug companies are likely to welcome a firm signal from the FDA that will reduce the questions surrounding the new field. They are also likely to applaud the agency’s promise that voluntarily submitted information won’t be used in decisions about drug approvals. “The patients and the industry need ground rules because the correct use of this data … is going to be critical for it to be of benefit,” says Stephen Friend, a senior vice president at Merck & Co.

According to the draft guidelines, when a drug company expects to include genetic testing information on the label, FDA reviewers will want to see all of that testing and its results. The FDA also wants full information about any pharmacogenomic testing done in developing a new drug if the manufacturer used such testing to help decide which people received the drug in clinical trials. Choosing particular people to participate in trials may be a key factor in explaining the company’s evidence that the medicine is safe and effective. If the drug is approved, doctors may be asked to use the genetic test performed by the drug maker to decide which patients should get the medicine.

In other cases, the FDA says, the agency will ask companies to voluntarily submit more general research in pharmacogenomics. The FDA plans to use such information to gain better understanding of the field. That’s “important, because there’s a lot of uncertainty about the significance of data in these areas,” says Chris Webster, director of regulatory affairs for Millennium Pharmaceuticals Inc., which has an aggressive pharmacogenomics program.

In the drug approval process, the FDA says it plans to continue using its traditional criteria, evaluating the drug’s safety and effectiveness in “the overall indicated population” even if there are also genetic testing results that show variations in effectiveness for certain groups. So far, the agency has tended to use the genetic-test information on the drug’s label in language that describes its implications and points out precautions.

But if a drug company develops a genetic test along with the medicine and wants to target the drug only at people with certain genetic signatures, the FDA will also consider those applications, the draft guidelines say.