Genomics and Personalized Medicine : Challenges

by Food and Drug Administration (FDA)

(Page 3 of 3)

What Is the FDA's Role?

In 2002, the FDA held a workshop for industry on pharmacogenomics in drug development and regulatory decision making. "The agency has taken a leadership role by initiating discussions about pharmacogenomics and gathering input on how the FDA can best promote the science," Woodcock says.

In March 2005, the FDA released a guidance on the agency's current thinking about pharmacogenomics and on data submission. The FDA considers pharmacogenomics to be a major opportunity on the critical path to new medical products. For now, most pharmacogenomic data are of an exploratory or research nature and are not required under existing regulations; however, voluntary submissions are encouraged.

"This way, industry can meet informally with the FDA and talk freely without concern that the data will be used inappropriately for regulatory decision making and at the same time drug developers will learn more about the agency's expectations," says Frueh. The FDA is working on other guidances on how to develop genomic tests and drugs together and on the quality of DNA analysis.

"From FDA's perspective, genomic data has the potential to help us understand how a drug works and for whom, which helps in assessing the risk-benefit ratio," says Yvonne Dragan, Ph.D., director of the division of systems toxicology at the FDA's National Center for Toxicology Research (NCTR) in Jefferson, Ark. Scientists there are active in pharmacogenomic research. For example, FDA experts found that women with breast cancer who have a slow version of the gene SULT1A1 have lower survival rates on a typical post-surgery regimen of tamoxifen and may need different doses of the medicine.

"The FDA also plays a critical role in making the tools available to put the science into practice," Dragan says. In December 2004, the FDA cleared the AmpliChip Cytochrome P450 Genotyping Test. Doctors can order this test to gain information on whether the patient has mutations in a gene that's active in metabolizing many types of drugs, including antidepressants, antipsychotics, beta-blockers, and some chemotherapy drugs.

In August 2005, the FDA cleared the Invader UGT1A1 Molecular Assay, which also detects variations in a gene that affects how certain drugs and drug metabolites are broken down and cleared by the body. Variations in the gene can influence the patient's ability to break down the major active metabolite of Campostar (irinotecan), a drug for colorectal cancer. The inability to break the metabolite down can lead to increased levels of it in the blood and a higher risk of side effects.

"The FDA's role in personalized medicine is one of bringing balance to an evolving science in a way that reaps the benefits, but also doesn't inhibit its growth," Lesko says. "It's a flexible approach, and we have been engaging industry in continuous dialogue, issuing guidances as the science matures, and continuing to focus on the impact pharmacogenomics can have on public health. We want to get the tools out there so that doctors can make informed decisions and so they will be able to interpret what value and meaning genomics brings for their patients' medical care."

What Are the Challenges?

The FDA will be working to advance its capabilities to analyze and interpret genomic data that come into the agency, and to communicate the relevant information in an understandable way in drug labels, Lesko says. "We will also be working to coordinate the efficient and timely review between centers in the agency as drugs and tests are co-developed. More and more, genetic tests will be used along with drugs."

A major challenge, Lesko says, is that there is a general lack of familiarity with pharmacogenomic data because the science is so new and is constantly evolving in new ways. "I think it will require a new way of thinking about individualization, and some people will be resistant to change given the challenges of understanding the information," he says.

Relling agrees. "Most clinicians will be resistant to the routine use of pharmacogenomics in medical care," she says. "Incorporating pharmacogenomics into prescribing decisions will represent a major change for the health care community."

"The hope for the future is that every patient will have a blood sample and we can extract DNA and do a test to get a genetic profile. Then we could use the profile along with clinical information to make care better," she says. "But it's not going to be that simple. It's going to make practicing medicine more complicated. Most of the world uses a trial-and-error approach. So changing will come at some cost to society."

Experts say that incorporating pharmacogenomics into everyday medicine will also take time. It is happening in mostly academic medical institutions like St. Jude's. Even though the Human Genome Project has sequenced a map of the body's genes, that doesn't identify all the targets in drug discovery, Relling says. "Many more studies will be needed to identify which gene variations are related to drug response and to prioritize them." The Pharmacogenetics Research Network of the National Institutes of Health is a nationwide collaboration of scientists committed to studying the effects of genes in response to a variety of medicines, including antidepressants, chemotherapy, and drugs for asthma and heart disease.

"In cancer, we're also dealing with diseases that require at least 10 years of follow-up so we can see the long-term outcome for patients," she says. "The public needs to understand that it may take years before we know whether individualizing doses based on genetics improves the long-term outcome of cancer patients because of the nature of the disease. Careful collection of clinical information and studies with large numbers of patients will be required," Relling says.

"In the future, legal assurances will be needed so that insurance companies can't use genetic information to discriminate against people who have a genetic risk for health problems," she says.

Caldwell says there also may be reluctance on the part of doctors and researchers to pay for and conduct genetic tests until someone shows that these tests make a difference. "Multiple genes can influence patients' response to the drug, as well as other drugs given at the same time, and various environmental factors," Caldwell says.

Experts say that another challenge will be whether drug companies decide that there is enough financial benefit from therapies that help only small segments of people.

"We're really at the dawn of this," says Caldwell. "We will make new discoveries about genes that are important in drug treatment and we will see more diagnostic tests. The next step now is proof of concept — proving the difference that personalized medicine makes."

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.