The 5 Myths of Pharmacogenomics - Pharmaceutical Executive


The 5 Myths of Pharmacogenomics

Pharmaceutical Executive

2. PGx Is for Tomorrow The second most common misconception is that pharmacogenomics is a technology that will not be used by doctors in clinical practice for at least five to ten years. The reality is that physicians have been using some pharmacogenomic tests in clinical practice for several years.

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GlaxoSmithKline's drug Purinethol (mercaptopurine) is commonly prescribed for leukemia in children. Yet one in 300 children has a gene defect for the enzyme thiopurine methyltransferase (TPMT), which normally inactivates the drug. It is now standard practice to give a TPMT test to screen for kids at risk of developing life-threatening bone marrow toxicity. Oncologists also routinely use HercepTest on metastatic breast cancer patients to identify candidates for Herceptin therapy. Many other pharmacogenomic tests are in development that will identify patient responses to other cancer therapies.

Several companies, including Genelex and Roche Diagnostics, offer a series of PGx screening tests for cytochrome p450 (CYP) enzymes and pathways. Produced in the liver, the enzymes metabolize more than half of all marketed drugs. About 5–10 percent of Caucasians have defects in those pathways that may reduce the effectiveness or increase the toxicity of certain categories of drugs, including analgesics such as morphine and Demerol (meperidine), anti-arhythmics, and antidepressants like Prozac (fluoxetine).

One high-profile case involving cytochrome p450 enzymes dramatically demonstrates the promises and pitfalls of pharmacogenomic testing. In 1999, FDA reported the Prozac-related death of Michael Adams-Conroy, a nine-year-old boy with mental illness. The medical examiner concluded that the boy's adoptive parents had administered an intentional Prozac overdose. Indicted for murder, the parents sought a second medical opinion, which found the boy had a CYP 2D6 gene defect, resulting in poor drug metabolism and a toxic accumulation of his prescribed Prozac dose.

The murder charge was dropped, and in a Fortune article (10/02), Michael's mother, Jayne Adams-Conroy, stated: "After Michael died, we found out that there were tests to spot enzyme deficiencies that can cause adverse drug reactions. I felt devastated when I heard that. It should be the norm that the tests are used whenever there are concerns about possible side effects."

3. PGx Is Dependent on Technology Many in the industry also believe that the only major factor driving the adoption of pharmacogenomics in clinical practice is the rate at which PGx technology develops. Despite the highly profiled Adams-Conroy case, CYP tests-unlike the TPMT test and HercepTest- are seldom used in clinical practice, although they are commercially available.

One possible explanation is that the CYP technology is not as accurate or drug-specific as the other two tests. Although it is likely that technology advances will help drive overall adoption, there are several other important and interdependent factors that are driving the adoption of PGx testing in clinical practice.

Regulations. One of the major reasons that HercepTest has become standard clinical practice is that FDA required in the product labeling that it be given before prescribing Herceptin. In a 2002 Pharmacogenomics Journal article, FDA regulators said. "It is likely that the FDA would not have approved Herceptin without the accompanying diagnostic [pharmacogenomic] data." The agency is also encouraging pharma companies to conduct PGx research and submit the data to a proposed "Interdisciplinary Pharmacogenomic Review Group" that is separate from the drug approval process. (See PE's Washington Report, June 2003.) Other international regulatory bodies are also developing PGx regulations.

Reimbursement. US reimbursement for diagnostics often follows regulatory or governmental policies. For example, most third-party payers reimburse for HercepTest. In fact, they typically require the test before reimbursing for Herceptin. In cases where there is no regulation or government policy, payers often follow "the standard of care." Consequently, the TPMT test is typically covered, while CYP tests usually are not.

Most payers view PGx testing as another medical technology that will ultimately increase their costs. However, a few are conducting studies to ascertain if they can "cherry pick" pharmacogenomic tests to reduce drug costs in carefully selected cases. United Healthcare is conducting a study with Interleukin Genetics to develop a PGx test that could exclude patients who may be non-responsive to certain high-cost rheumatoid arthritis drugs. Payers are thus likely to selectively support and use pharmacogenomic testing and data.


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