F.D.A. Issues a Guide to Gathering Genetic Data That May Personalize Drug Therapy
By ANDREW POLLACK
Published: March 23, 2005
The Food and Drug Administration took a significant step yesterday toward the development of so-called personalized medicine, in which drugs would be tailored to individuals based on their genetic profiles.
The agency issued guidelines for pharmaceutical companies intended to encourage them to gather and submit information about how genetic variations affect the way people respond to their drugs.
Drug companies have been somewhat reluctant to do this, agency officials said, from fear that the government might use the information to limit the market for their drugs. Drug makers have also worried that the F.D.A. might block approval if, say, a drug was shown in a laboratory test to activate a gene that might be involved in cancer.
To reassure drug companies, the F.D.A. has said that most of the genetic information will not be considered in regulatory decisions. Instead, the agency said, the information will be used to help the agency learn about the new science of tying genetic variations to drug response, a field called pharmacogenomics or pharmacogenetics.
''Companies either weren't doing that work because they weren't understanding its regulatory status or they weren't submitting it to us,'' Janet Woodcock, the F.D.A. acting deputy commissioner for operations, said in an interview. She added, ''I can't tell you how important it is for medicine that we move into this paradigm.''
Edward Abrahams, executive director of the Personalized Medicine Coalition, a Washington group of companies, academic institutions and others that aim to promote the new field, hailed the F.D.A. guidelines as a milestone. ''The government is now the advocate for personalized medicine in an official way.''
Pharmacogenomics is still in its infancy. It is well known that a particular drug might work for some people but not for others, or might cause side effects in some people but not in others. But so far there has been little testing of patients for genetic variations that could predict such reactions, which would allow drugs to be given to appropriate patients and reduce side effects.
The most-cited example is Genentech's drug Herceptin, which is given to women with breast cancer only if their tumors have a particular genetic characteristic that increases the probability that the drug will be effective. But there are few other examples of pharmacogenetics in actual medical practice.
So far, little is known about which genetic variations predict response to which drugs, and tests are not widely available. Even when such information is known, drug companies have been somewhat reluctant to pursue the practice, some authorities say, because it could potentially confine their drug to a subset of the population, reducing potential sales.
''When I have consulted with pharmaceutical companies, there's a very strong resistance to the development of a test to be marketed with their drug,'' said Richard Weinshilboum, a pioneer in pharmacogenetics at the Mayo Clinic.
That attitude now seems to be changing, however, because of recent safety problems with some widely used drugs and because cancer drugs in particular seem to be more effective when directed at tumors with particular characteristics.
''It excites us and it's here,'' Steven Paul, executive vice president for science and technology at Eli Lilly & Company, told an audience at a biotechnology industry meeting in San Diego yesterday.
The new F.D.A. guidelines do not deal with the use of such tests by doctors in the field but rather the drug companies' submission of data to the F.D.A. Submission of most such data would be voluntary and the information would not be used in regulatory decisions.
There are exceptions. If a drug company restricts the patients in a clinical trial to those with a particular genetic marker, that information would have to be part of the application for the drug's approval. Also mandatory is submission of information on so-called valid biomarkers, genetic variations whose correlation with drug response is well understood and widely accepted.
An example of such biomarkers is the variations in a gene called CYP2D6 that correlate with how quickly people eliminate some drugs from their body. Those who metabolize quickly might need a higher dose and those who do so slowly might get by on a lower dose. The F.D.A. recently approved a test from Roche that measures variations in that gene and in another one involved in drug metabolism.
The new guidelines are final versions of a draft issued in November 2003. Agency officials and outside experts say the final guidelines differ little from that draft. Mainly, the final guidelines eliminate uncertainty.
''That will make a lot more companies comfortable about going out and doing things in this space,'' said Richard S. Judson, chief scientific officer of Genaissance Pharmaceuticals, a company in New Haven that develops drugs and pharmacogenomic tests.