Washington Editor

WASHINGTON - Medical practices that are targeted to individuals on the basis of their specific genetic makeup, or personalized medicine, will soon be a reality, and government, industry, researchers, practitioners and the public must be prepared, officials and health care experts said at a forum here Wednesday.

Under the concept of personalized medicine, results from genetic tests are correlated with drug response, disease state, prevention or treatment prognosis to help physicians individualize treatment for each patient with greater precision.

"We have the technology now to make health care much more personal and much more efficient. We just need to apply it to the tasks at hand," Health and Human Services Secretary Michael O. Leavitt said.

Those tasks, he said, include developing evidence-based standards for measuring and improving quality of care, building systems of health information technology to make patient records available when and where they are needed, using health IT systems to gather medical evidence from the day-to-day practice of medicine so that clinicians can make the best decisions for each patient, and ultimately using personal genetic information to tailor treatments more effectively to each patient.

Leavitt's remarks came in conjunction with the release of HHS's first report on personalized medicine: "Personalized Health Care: Opportunities, Pathways, Resources," which outlines the work that lies ahead for the government, the biotechnology and pharmaceutical industries, and other stakeholders.

The report also provides brief descriptions of various federally funded projects under way related to personalized medicine.

The potential for predicting health, for preventing and preempting disease, and for personalizing treatment according to each person's unique biology is "huge" right now, Leavitt declared.

Although the Human Genome Project, the international, public effort to sequence all 3 billion DNA base pairs of the human genetic blueprint, was completed in April 2003, the research gleaned from that project has "just left the starting line" and "its pace of discovery is still accelerating," he said.

Personalized medicine already is a reality in some respects, HHS stated in its report.

For instance, women with breast cancer can have a predictive test that identifies whether a tumor bears a genetic signature for a certain human epidermal growth factor (HER-2). A person who tests positive for the HER-2 gene is a good candidate for Herceptin (trastuzumab), which reins in the excess HER-2 and nearly halves the person's risk of disease recurrence.

A diagnostic test is available for patients with chronic myelogenous leukemia that can detect the presence of Bcr-Abl. People who test positive for the mutant gene are generally prescribed Gleevec (imatinib mesylate), which binds specifically to the faulty gene's product and inhibits its cancer-causing action.

Women who test positive for the BRCA1 or BRCA2 gene variations, which puts them at a higher risk of developing breast and ovarian cancers, now can take preventive measures, such as having ultrasound imaging or biomarker detection testing, or more aggressive actions, such as taking chemopreventive agents or undergoing prophylactic surgery to remove at-risk tissue.

On Aug. 16, Leavitt noted, the FDA asked makers of the blood-thinning agent Coumadin (warfarin) to include in product labeling a recommendation to have patients undergo genetic testing to determine a reasonable dosage for the person to help optimize the use of the drug and lower the patient's risk of bleeding complications from the product.

On Monday, the agency approved a genetic test to identify patients with certain gene variants that puts them at a higher risk of bleeding if they take the product.

The practice of using genetic information to individualize drug therapies, or pharmacogenomics, will help drug developers, researchers and clinicians determine "as rapidly as possible" who is at risk for adverse events associated with certain medications and why, said Janet Woodcock, FDA's deputy commissioner and chief medical officer.

"We have to figure out who is going to benefit from what rather than one size fits all," she said.

But, warned Daniel Mendelson, president and founder of Avalere Health, all stakeholders must come to grips with the commercial implications of public policy decisions made about personalized medicine.

One reality that the biotechnology, pharmaceutical and device manufacturing industries must face, he said, is, "If you know who is going to benefit from the therapies, you are going to be selling fewer units of them."

That fact creates a "huge financial disincentive" for product developers to engage in the personalized medicine concept, said Mendelson, who served as associate director for health at the Office of Management and Budget during the Clinton administration.

In a reimbursement environment in which products are paid for per unit, if 80 percent of patients are not going to benefit from a particular therapy, then a firm loses 80 percent of its market, he said.

"This is going to shrink the size of markets, and we have to get comfortable with the fact that in some cases it is going to be appropriate for us to pay more per unit for the products if we actually want to see them developed," Mendelson said.

Knowing who is going to benefit from a certain therapy also has important implications for commercial strategies in the insurance market, he said.

Since insurance companies profit by avoiding risk, they are more inclined to select healthier patients who may not need expensive therapies, Mendelson said.

Employers are increasingly less interested in offering health care coverage to their employees as insurance costs increase, he noted.

"You have unprecedented new levels of patient cost sharing," he said. "Patients are being asked to pay more and more, and the basic insurance concept is dissolving."

Since personalized medicine inevitably will shrink the number of people who are eligible candidates for certain therapies, while at the same time fewer patients are being covered by insurance, Mendelson said, "I would argue that this is going to require a very fundamental shift in the way that commercial developers as well as policymakers think about pricing."

Biotechnology products in particular, he said, "cannot exist in the marketplace without an insurance system. It just won't happen.

"We need to be thinking about reimbursement much more broadly than the current per-unit concept," Mendelson said.

Product development also will be affected, "and is already being affected," by the integration of new technologies, such as genetic testing and molecular imaging, he said.

"With that integration of technology, development is going to become, and is becoming, I would argue, much more expensive," Mendelson said.

The FDA, he noted, also is demanding more information about biomarkers, which also is increasing the costs of clinical development.

As development costs go up, Mendelson said, companies will be forced to choose what products they can and cannot afford to develop.

"I think already you see that emerging in the marketplace," he said.

Personalized medicine, Mendelson said, will challenge the biotechnology and pharmaceutical industries in a "very fundamental way" that will force companies to make changes that are not easily made, especially by the larger firms, which he called "more bureaucratic than government."

"Personalized medicine is one of those issues on which it is absolutely critical that very senior people, board level, really understand it, and to make sure that those insights get permeated throughout the organization," he said. "It is not something that can be taken off and put on the side, because it touches on all major aspects of a company."