Genomics and Personalized Medicine : What Are the Potential Benefits?

by Food and Drug Administration (FDA)

(Page 2 of 3)

The main benefit of pharmacogenomics for consumers is the availability of drugs that have a greater chance of benefit in terms of treating illness, says Janet Woodcock, M.D., the FDA's deputy commissioner for operations.

"Consumers want effective treatment and minimal side effects," Woodcock says. "They want to know that they're getting the right drug and the right dose. There are some people who feel like they are always experiencing bad side effects from drugs, and in some cases, genetics plays a role. If we could find out who the susceptible people are so they can avoid the risk, we could target a drug more appropriately instead of removing it from the market."

The hope for the future is that through personalized medicine, doctors and patients will be able to make better-informed choices about treatment. Genetic information could lead them to decide which drug to use, whether to lower a dose, or whether closer monitoring of the patient for side effects is needed.

The most common approach to drug treatment now is that doctors give all patients with a given disease the same drug and an average dose, evaluate how it works, and then make adjustments as needed. "But with life-threatening illnesses such as cancer and heart disease and with drugs that can have serious side effects, getting it right the first time is critical," Relling says. "Rather than using a trial-and-error approach, we want to be able to analyze a patient's genetic profile and prescribe the best therapy and dose from the start."

With technology called gene expression profiling, researchers can determine which of the genes that activate or break down drugs are active in a particular patient. "This could show who is most likely to benefit from a drug and who may have a toxic reaction," says Relling, who, with colleagues at St. Jude's, has led some of the world's first pharmacogenomic studies in children with acute lymphoblastic leukemia (ALL). This type of cancer starts in the bone marrow, the soft, spongy inner part of the bones. The disease can move quickly into the blood or other parts of the body such as the liver, the spleen, and lymph nodes.

"Chemotherapy cures about 80 percent of ALL cases," Relling says. "But treatment fails in the remaining cases because the patients' cancer cells are resistant to chemotherapy drugs or because of fatal toxicities of chemotherapy. The hope is that cure rates can increase if doses are individualized to maximize cure or minimize adverse effects."

Relling and her colleagues at St. Jude's routinely use genomic tests to differentiate between various subtypes of ALL, which respond to chemotherapy in different ways.

"We have genetic studies built into the treatment protocols as part of our research program," Relling says. "We measure how much of the drugs are in the children's leukemic cells and their blood. We perform MRI imaging of their hips to see if there is any bone toxicity, and we follow side effects and leukemia status for two and a half years while children are on chemotherapy. We put together all of this detailed information with genetic testing and identify which genetic profiles predict side effects or relapse. We not only look forward, but we also look back at data we've collected from years ago. We started collecting DNA from patients in 1986 because we anticipated that this genetic revolution was coming."

This type of research could make drugs for many diseases more effective, including heart disease, diabetes, depression, and asthma, says Michael Caldwell, M.D., head of the Personalized Medicine Research Center at Marshfield Clinic in Marshfield, Wis. Caldwell and his colleagues have investigated the role of genetics in a number of drugs, including the anti-clotting drug Coumadin (warfarin).

"You can give the standard dose of warfarin and some people are just fine, while others will have significant complications such as bleeding into the brain," Caldwell says. "We confirmed work by others that if you identify a patient's genetic make-up, we can get a better handle on the appropriate dose much earlier."

Caldwell says he believes that the field of personalized medicine will continue to grow in the interest of patient safety. "I think we will gain a better ability to predict adverse reactions earlier in drug development." And decreasing adverse events and increasing successful therapy could lower the cost of health care, says Allen Roses, M.D., senior vice president for genetics research at GlaxoSmithKline (GSK).

"Medicines are often marketed broadly because the patients likely to benefit from a particular drug could not be separated from the patients who would not respond well," Roses says. "But it could be more economical to make informed decisions based on inherited characteristics and the variability that exists in the population in order to produce safer and more effective drugs."

Roses says the potential of pharmacogenomics for drug companies lies in the discovery stage — being able to create new drugs based on genetic information. A better understanding of genetics and disease helps identify new targets for drugs. This could bring drugs to the market sooner.

"If we find in clinical trials that 90 percent of people don't respond to a drug, we can look at groups of nonresponders that have the same genetic characteristics and conduct further research," Roses says.

GSK routinely collects DNA from patients who provided informed consent for pharmacogenomic studies in its U.S. clinical trials. "This will help identify factors that may predict drug response," he says. "If only some people are experiencing adverse events and DNA is available for those patients that will help tell us something about how to lower the risk of side effects."

"In clinical trials, drugs that may be harmful to only a small number of patients might be able to be used if we find out which genes are associated with the adverse responses," Roses says. "The drug could be approved for people with a low risk of adverse events."

About the Author

www.fda.gov
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.