Discovery Genomics program at the Duke Clinical Research Institute

Duke’s Discovery Genomics center rides pharmacogenomics wave
2010-12-14 08:00

By Jessica Wapner

Last year, a research project led by David Goldstein of Duke University found that variations in the IL28B gene had profound effects on how people with hepatitis C respond to treatment. More specifically, those with certain mutations were twice as likely to respond to prolonged drug therapy (Nature 461, 399–401, 2009). The link's impact on patient care and drug development served as a wake-up call for investigators to ramp up efforts to identify genetic variants associated with disease occurrence and treatment response.

Spurred by this homegrown insight, investigators at the Duke University School of Medicine in Durham, North Carolina decided to form Discovery Genomics. The new center—a collaboration between the Duke Clinical Research Institute (DCRI) and the university's Center for Human Genome Variation (CHGV)—launched in October. Although projects within the university are its main focus, Discovery Genomics also operates as a fee-for-service business for pharmaceutical companies interested in finding genetic variations associated with drug efficacy and toxicity
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DURHAM – Duke University is looking to capitalize on its extensive research into genomics by offering to provide genetic analysis in clinical trials.

The Discovery Genomics program at the Duke Clinical Research Institute, Duke’s clinical research organization, will offer pharmaceutical companies the opportunity to study the genetic composition of clinical trial participants. That information could tell companies whether a drug will work better in some people and not others or whether certain individuals are more prone to incurring side effects.

DCRI is among the first, if not the first, to develop a program for analyzing the genetic sequences of clinical trial patients.

“It is now possible to screen a genome for variations that have strong influences on therapeutic responses and susceptibility to adverse events,” says David Goldstein, director of Discovery Genomics. “An adverse event that severe can make it difficult to win approval. We can use genetics to see if a pattern can be found.”

The decision by DCRI to offer the new service comes after work done by Goldstein and his colleagues at the Duke Center for Human Genome Variation identified how genetic variations affected the treatment of hepatitis C patients.

The course of treatment for the viral infection typically consists of 48 weeks worth of drugs interferon and antiviral ribavirin. The treatment only works in about half of patients and can cause severe complications, including anemia. Many patients drop out before completing the treatment regimen.

Goldstein and his team, working with Schering-Plough, which helped fund the study, analyzed the blood samples from clinical trial participants taking the drug and found genetic variations within patients who benefited from the treatment and within patients who suffered from side effects.

Using that information, LabCorp developed a test for the genetic variation to help hepatitis C patients determine whether they are likely to benefit from the drug or are likely to incur side effects, helping them decide whether they want to undergo the treatment.

Dr. Bob Harrington, director of DCRI, says such revelations are particularly exciting for physicians, who are now better able to steer patients to the best treatment options.

Dr. Kevin Schulman, associate director of DCRI, says this is the foundation needed for personalized medicine to come to fruition.

Personalized medicine is a concept in which a patient’s genetic information is used to identify the best courses of treatment, as well as to identify diseases the patient is more predisposed toward and to work toward preventing those diseases.

Geoff Banks, president and founder of ClinPharm Consulting, says there has been a lot of talk about personalized medicine, but the idea has not been readily implemented due to cost and complication. “I think it’s good that Duke is doing this,” he says. “I think there is a need in the industry to start moving in this direction and to have these services available.”

The genetic analysis work is benefiting from the quickly dropping cost for gene sequencing and analysis.

A genomewide association study to determine which patients are more likely to benefit from a treatment would take about two to three months to complete and cost about $500,000, while a study to determine which patients are more likely to suffer side effects takes about three to five months to complete and costs between $125,000 and $750,000.

Such studies could, however, end up reducing the market for particular drugs by identifying the subset that most benefits.

But, says Tom Kaminski, in business development at DCRI, such studies could salvage a drug that has failed a critical trial by identifying appropriate patients or by helping pharmaceutical companies find other uses for their drugs. DCRI staff currently are looking back into some clinical trials for failed drugs to see if trial participant genetics played a role and if there are any drugs that can be salvaged.

So far, the U.S. Food and Drug Administration has not weighed in on genetic analysis of clinical trial participants, though Goldstein says that based on conversations he has had with the regulatory body, he believes the agency could look to use it to assure patient safety.

Read more: Duke expands genetics research Triangle Business Journal