Since the historic decoding of the human genome, there has been a lot of buzz about pharmacogenomics (PGx), defined simply
as how people respond to drugs based on their genes. Within the pharma industry, researchers are excited about PGx's potential
to accelerate drug discovery and development by identifying better drug targets, establishing preferred patient populations,
and improving safety and efficacy profiles. But there has been much less excitement among industry's business executives,
especially marketers, many of whom have concerns about PGx's business impact.
The emerging field has the potential to dramatically change the pharma business, perhaps even more than the way managed care
has altered the industry's marketing model. Consequently, executives need to understand the implications and applications
of pharmacogenomics today-because they have already begun to influence the use and marketing of pharma products. Unfortunately,
many executives have misconceptions, misunderstandings, and misgivings about pharmacogenomics. This article attempts to put
the emerging technology into perspective by identifying and debunking five common myths.
1. PGx Is Only a Research Tool
Many industry execs believe that pharmacogenomics is primarily a research and development tool used to identify drug targets
more quickly and that it has yet to have a role in the success or failure of marketed drugs.
In the broadest sense, PGx has both research and clinical applications: to identify drug targets (research) and to predict
the safety and efficacy of drugs in individual patients or groups of patients (clinical). The second application is referred
to as pharmacogenetics. For the purposes of this article, the term pharmacogenomics encompasses the subgroup of pharmacogenetics.
The first half of the myth is based on experience: Most major pharma companies use PGx to identify new drug targets and to
select appropriate study patients. But there are several cases that demonstrate how pharmacogenomic differences have affected
products' commercial prospects. For example, in 1998, FDA forced Hoechst Marion Roussel (now Aventis) to withdraw its $600-million-a-year
anti-allergy medication Seldane (terfenadine) from the market because of pharmacogenomic differences in a very small segment
of patients. Fewer than 0.5 percent of all people have a variant CYP3A gene that makes them unable to metabolize Seldane in
the presence of the antibiotic erythromycin, resulting in severe cardiotoxicity. If the company had had a pharmacogenomic
test to identify the small population of adverse reactants at the time, Seldane may have remained on the market. Consequently,
Aventis was forced to focus its marketing efforts on another anti-allergy medication, Allegra (fexofenadine).
Researchers now believe that many recent drug withdrawals-Bayer's cholesterol agent Baycol, Wyeth's appetite suppressant Redux,
and GlaxoSmithKline's oral diabetes agent Rezulin-may have been a direct result of pharmacogenomic differences among small
patient subpopulations. Many more potentially useful and lucrative drugs may have never reached the market because poor responders
negatively affected the overall safety or efficacy data.
Isolating pharmacogenomic responses can also rescue a drug. Genentech found that its breast cancer drug Herceptin (trastuzumab)
was effective only in the 25 percent of women whose tumors generated excess proteins from a HER2 gene.
Consequently, the company saved the "failing" drug by coupling it with a PGx test (HercepTest) to identify potential responders.
GSK's Ziagen (abacavir), an important HIV treatment, may precipitate a severe and potentially fatal hypersensitivity reaction
in approximately 5 percent of people with a certain genetic marker. To rescue the product's $200 million in annual sales,
GSK is currently working with FDA to develop a PGx test to identify patients likely to have the adverse reaction.