Indiana playing trailblazing role in drive to tailor pharmaceuticals to genetic makeup of individuals

Prescribe the wrong dose and some drugs won’t work. Or the patient is as good as dead.

Consider the rat-poison-turned-blood-thinner warfarin, also known as Coumadin. Too much and a
patient can bleed to death, too little and he can throw a clot and have a stroke.

Given the considerable consequences of improper
dosing for patients—and health insurers—researchers are looking intently into how a person’s
genetic underpinnings determine how drugs are metabolized.

And it turns out Indiana is becoming not only a hotbed of "pharmacogenomics" research,
but also a trailblazer in finding practical ways to use it on the practitioner level.

"We’re looking at a paradigm shift in health
care," said Michael D. Kane, lead genomic scientist at Bindley Bioscience Center at Purdue University.
Kane recently helped found Genomic Guidance LLC, which plans to bring low-cost DNA screening on the clinical
level to help predict how a person is likely to respond to anticoagulants and other drugs.

The field has been researched at Purdue and Indiana universities for years, but came into public
view last year when pharmacy benefits manager Medco Health Solutions Inc. announced it would add a pharmacogenomics
research center at its $140 million automated pharmacy under construction in Whitestown.

Medco will call it the easier-to-pronounce Personalized
Medicine Research Center. With collaboration from leading university researchers in Indiana and
elsewhere, the center will study genetic and clinical drug testing and medical claims
data. The center will be overseen by Felix Frueh, a genomics authority formerly at the U.S. Food and
Drug Administration.

The
New Jersey-based pharmacy benefits manager envisions patient files including a genetic profile related to how quickly
the patient metabolizes a particular drug. That data could be referenced when a person is prescribed a blood thinner, pain
reliever or cancer drug.

A physician could be told, "Did you know your patient is a poor P2C metabolizer?" said Medco spokeswoman Ann Smith,
referring to an enzyme the body uses to metabolize a drug. Genetic information "can be used against
a myriad of drugs."

Medco and Mayo Clinic already are studying genetic considerations in warfarin dosing. And Medco and Burlington, N.C.-based
LabCorp are studying breast cancer patients who take tamoxifen.

Some pharmacogenomics research also involves identifying whether genetics make some people more
likely to suffer side effects when they take two kinds of drugs, or whether one drug cancels out the
other.

For example, Indiana
University pharmacogenomics researchers in recent years found that some women with a particular genotype
may not receive the full benefit of the breast cancer drug tamoxifen while taking antidepressant paroxetine—better known
as Paxil.

The focus on patient genotypes is intensifying at Eli Lilly and Co. under the moniker "tailored therapies." For
example, subsidiary ImClone Systems has zeroed in on genes of certain patients for which its Erbitux
cancer drug is most effective.

It’s all part of a trend away from the focus on blockbuster drugs to developing versions of a particular drug tailored to
patients with varying metabolism types, said David Johnson, president and CEO of BioCrossroads, the Indianapolis-based life
sciences industry group.

One of the best examples is the breast cancer drug Herceptin, Johnson said. Its maker, San Francisco-based Genetech Inc.,
focused on a population of women with a special receptor—a relatively small population of women. But for this group,
the drug has performed exceptionally well in turning off cancer cell production.

"Everybody is looking at whether we could
really deliver more drugs like that," Johnson said.

And the drug that works tends to be the one insurers will pay for, he noted.


Progress, at a cost

But all of these tailored therapies require
capturing a patient’s genetic information, and the costs and logistics may prove more difficult than
some of the science involved in your average single-nucleotide polymorphism.

A study published early this year in the Annals of Internal Medicine on using pharmacogenomic
information in warfarin patients concluded that, at current costs, routine genotyping before warfarin
dosing is not cost-effective.

The University of Cincinnati Medical Center, Massachusetts General Hospital and Washington University in St. Louis concluded
there would be "minimally improved" survival rates. Yet costs would rise dramatically, at $172,000 per "quality-adjusted
life year" versus the "generally accepted societal threshold" of $50,000.

Purdue scientist Kane argues that test cost
assumptions in the study are high. The company he co-founded in January, Genomic Guidance, is working
on a one-time DNA screening for anticoagulants that will provide results in less than 90 minutes and
cost less than $30.

"None
of this is going to happen until it’s a value proposition for everybody" in health care, Kane said. He contends that
Genomic Guidance’s on-site DNA screening system and integrated data management will meet that test.

Genomic Guidance is based at Ohio Northern University,
in Ada, Ohio, but the software to provide doctors and pharmacists with predictive drug efficacy and toxicity
based on a patient’s genotype was developed by Kane and Purdue information technology experts John Springer
and Nick Iannotti. Their "GeneScription" system was developed under a grant from Microsoft Corp.

But cost isn’t the only obstacle—so are
privacy concerns. Genetic testing is still a dicey area, with some detractors concerned that insurance
companies will use information to determine one’s predisposition for certain diseases and jack up rates or
reject those in higher risk categories.

Public concern has been so strong that Congress acted. Last May, then-President Bush signed into law the Genetic Information
Nondiscrimination Act, which prohibits U.S. insurance companies and employers from discriminating on the basis of information
derived from genetic tests.

Dodging privacy concerns

But the kind of DNA screening Kane is looking at does not attempt to determine disease risk. It
looks at whether a person harbors one or more single nucleotide polymorphisms shown to alter the rate
of drug metabolism and the efficacy of prescription drugs.

People concerned about privacy won’t have to have their results placed in medical records. They
could walk out of the clinic with a paper printout or have the information placed on an electronic data
card.

Kane said the system
could be placed first in a pharmacy, with the genetic information considered by the pharmacist while
conducting the usual review to see whether the medicine will interact with other medicines the patient is taking.

If the genetic screening software indicates
the prescribed dosing might not be appropriate, the pharmacist could alert the patient or doctor.

It remains to be seen how physicians and other
medical providers already weary of health insurers’ telling them how to practice medicine would react
to such pharmacogenomic guidance.