CEO SUMMARY: It may be gloom and doom today in the clinical laboratory industry, but long term prospects for diagnostic testing are brightening. Increased understanding of human genetics drives new discoveries about how and why the same drug affects individuals differently. Biotech companies like Oncormed, Inc. are positioning themselves to apply this knowledge to diagnostic testing.
HERE’S A NEW WORD that will soon be familiar to all laboratory executives and pathologists. The word is “pharmacogenomics” and it takes practice to pronounce it correctly.
In its simplest definition, pharmacogenomics refers to the process of using genetics-based technology to evaluate the affects of pharmaceutical compounds on the body.
“Pharmacogenomics actually can be used to describe two primary uses,” said Doug Dolginow, M.D., President and COO of Oncormed, Inc. in Gaithersburg, Maryland. “Drug companies consider pharmacogenomics as a method for using genomic information to discover and identify effective drugs. In this sense, it is a tool for creating new pharmaceutical compounds which they can bring to market.
“The other meaning of pharmacogenomics involves its clinical use for diagnostic and prognostic purposes,” he explained. “In this application, pharmacogenomics allows a clinician to identify specific ways that an individual might react to a specific drug.
“Obviously, the ramifications to healthcare are significant,” continued Dr. Dolginow. “Imagine being able to know, in advance, that a particular patient would benefit from a specific drug. Of equal value, what if the clinician knew in advance that a specific patient would have negative reactions to a drug?”
This is the reason why pharmacogenomics is a rising star on the healthcare horizon. For drug companies, pharmacogenomics promises to be the “philosopher’s stone” which alchemists believed could convert base elements into gold. For diagnostics companies and clinical laboratories, pharmacogenomics may unleash a new generation of diagnostic “super-tests” that bring immense value to both physicians and their patients.
It will be pharmaceutical companies that make this technology viable. They are under immense financial pressure to deliver sizeable revenues and profits to their stockholders. They will invest huge dollars to make pharmacogenomics pay off. Dr. Dolginow explains why.
“The drug industry needs to hit a home run with pharmacogenomics,” he observed. “The reason is simple. None of the major pharmaceutical houses has a blockbuster drug in the development pipeline. Traditional methods of drug development are now uneconomical or ineffective. The problem is further compounded by the fact that a number of highly profitable drugs are coming off patent.”
“80% of drugs currently fail in clinical trials. If you could do something about that failure rate, you are going to have a real impact on the economics of drug development.”
Fred Ledley, M.D.
President & CEO, Variagenics, Inc.
“Both developments mean that drug companies will struggle to generate increased revenues and profits,” he continued. “Pharmacogenomics is believed to have immense potential to change this situation and deliver big profit dollars to the drug companies.”
Laboratory executives should pay close attention to the comments of George Poste, the chief science and technology officer for SmithKline Beecham, PLC in London. “Pharmacogenomics is a logical progression of medicine. It will render healthcare increasingly rational, address the economic challenge of infinite demand versus limited resources. By identifying the relatively small proportion of the population that accounts for high costs, it will bring about a profound shift from reactive to proactive treatment.”
Poste, addressing 4,000 biotechnology researchers and companies at a June meeting, described current drug development methods as a “crap shoot.” He believes that pharmacogenomics will evolve, and “should become the rational foundation of rational therapy.”
Drug Development Pipelines
Poste’s comments confirm that major drug houses are rapidly incorporating pharmacogenomics into their drug development pipelines. The large amounts of money these pharmaceutical companies are investing in molecular and genetic research will rapidly advance the capabilities of this science.
Dr. Dolginow concurs, but thinks practical application in diagnostics will not happen overnight. “Despite all the headlines trumpeting the discovery of new genes which are related to specific diseases and cancers, we are several years away from tangible application of this knowledge,” noted Dr. Dolginow. “Pharmacogenomics is an emerging branch of science which has yet to deliver practical benefits. No company has yet to make money because of pharmacogenomics.”
“There are several reasons for this. New discoveries in molecular medicine usually take between five and 15 years before they evolve into effective and economical clinical procedures,” he said. “Another complicating factor is basic variation in the genetic make up of individual humans. Each time we identify a specific gene, individual variation complicates how that identified gene is expressed.”
“For example, we know the BRCAl gene is a predictor of breast cancer,” noted Dr. Dolginow. “But at the same time, we’ve already detected 400 different mutations in the gene. Scientists suspect that there may be as many as 8,000 mutations of that single gene!
“This range of genetic variation, combined with our current level of science, makes it difficult to precisely predict any individual’s true risk of developing breast cancer,” he said.
Dr. Dolginow is intimately familiar with this subject. Oncormed has positioned itself to be a resource that links pharmaceutical research with clinical trials involving human subjects. As a result, he comes in daily contact with thought leaders from both groups.
“Explosive growth of pharmacogenomic technology will happen after one drug company uses pharmacogenomics to develop a blockbuster drug like Viagra,” predicted Dr. Dolginow. “If that drug delivered $500 million or $1 billion per year in sales, then all the major drug companies would begin pouring hundreds of millions of dollars into this area of research.”
Pharmacogenomics Based On Polymorphism Variation
ALL HUMANS HAVE VARIATIONS in their genetic make up. These variations are called polymorphisms. Polymorphisms are increasingly believed to be responsible for why individuals react differently to the same drug.
The essence of pharmacogenomics is to first identify polymorphisms, then determine how these polymorphisms affect the way an individual reacts to a certain drug. For example, early research in Canada indicates that a subset of the apolipoprotein E (APOE) gene in Alzheimer’s patients is also a good indicator for the effectiveness of the drug tacrine. Individuals who were homogeneous for the APOE e4 allele had a much poorer response to tacrine than patients with other APOE sub-types.
This example indicates why polymorphisms and pharmacogenomics represent new areas of science which can dramatically increase the volume of diagnostic testing and add value to the clinician. This technology is several years away from widespread clinical usage. Nonetheless, laboratory executives should carefully watch developments in this field. Opportunities for profitable new lines of testing will appear at unexpected intervals.
Doubling Of Productivity
“Even now, the state of genetic research is already rapid,” he continued. “We see the same phenomenon as the silicon chip industry. Moore’s Law says that the productivity of a computer chip doubles and its price falls by half every two years. DNA-based technologies are experiencing the identical outcomes. Every two to three years, the productivity of basic processes doubles while the cost drops by half.
“But it must be remembered that our DNA-based technology is at the ‘vacuum tube’ stage,” he added. “It took a while for transistors to replace vacuum tubes. It took time to move transistors onto silicon-based chips. Even as DNAbased technology advances, it will take time for the marketplace to evaluate the economics and clinical efficacy offered by this technology.” THE DARK REPORT considers pharmacogenomics to be the convergence point for a variety of technologies which, in combination, will create the next several generations of diagnostic testing. We expect this convergence to create a new class of incredibly precise diagnostic assays. They will provide added value to both clinicians and patients, at a lower cost.
(For further information, contact Doug Dolginow, M.D. at 301-208-1888 or email to: email@example.com.)