DeCode Genetics and Illumina this week said they will work together to develop diagnostics for myocardial infarction risk, type 2 diabetes, and breast cancer, a step that will mark DeCode's entry into the test development arena. Celera Genomics this week separately announced advances in two large studies supporting the companies' plans to develop tests for assessing the risk of developing myocardial infarction.
Illumina will work with data from about 2,416 patients studied by DeCode Genetics to try to develop a SNP-based MI risk test with particular relevance to black Americans. The SNPs under study are not as predictive for black Africans.
Meantime, Celera Genomics and colleagues at Brigham Young University, in a study of more than 2,000 patients, have discovered two SNPs that Celera may add to a developing diagnostic that yields a risk assessment score for MI.
A recent report by the American Heart Association shows there were 865,000 new and recurrent myocardial infarctions in the United States each year between 1987 and 2002. This year, the AHA estimates that more than 700,000 million Americans, or about 3.5 percent of the population, will have a heart attack.
"We're talking months, not years. After publication, it is only a matter of time before a product [is] produced."
There is currently no test to determine a patient's risk of developing MI due to genetic predisposition. "The [example] of a heart attack in a mother or father [of the patient] gives you somewhere between a 30 percent and a 50 percent increase in cardiac risk," said Richard Stein, a spokesperson for the American Heart Association and director of preventive cardiology at Beth Israel Hospital in New York. "Certainly smoking, obesity, sedentary behavior — nurture, as opposed to nature, phenomena — still obviously play a major role in development of atherosclerosis, but clearly we take what is a very crude tool now to assess risk, in terms of family history or ethnic origins, which really are primitive ways of looking at genealogy," he said.
Any diagnostic developer with the goal of producing an MI risk test is likely going to need large studies to convince doctors that it will be useful in the clinic. "I think you would need to do at least a number of years' worth of clinical studies in humans to show me that this is something that would integrate into the clinical practice of medicine at the moment," said Stein. "At my level, I'm not seeing that the information [about genes related to heart attack] is there yet. "
Illumina and DeCode
Illumina said this week it will join with DeCode to develop diagnostic panels for its BeadXpress platform — set to launch before the end of the year — that will interrogate SNPs in the leukotriene A4 hydrolase gene associated with heart attack, as well as transcription factor 7-like 2 for type-2 diabetes and BARD1 for breast cancer. DeCode also tests patients involved in a phase III trial of its MI compound DG031 for the same SNPs.
DeCode and Illumina will share development costs and split the profits from sales of any tests. Each diagnostic panel will be submitted to the FDA after the platform clears, according to Illumina spokesman Bill Craumer.
Illumina has not yet determined which of these tests will be the first to be developed, Craumer said this week. "We plan on having at least one more of these kinds of deals [with another partner] by the end of the year," he said.
Information obtained from Illumina's MI test may help physicians decide how aggressively to treat patients found to be at risk of heart attack. Although the MI marker Illumina will use to develop its test is not directly related to drug response, DeCode is testing all participants in its phase-III trial of DG031 for leukotriene A4 hydrolase haplotypes.
However, a DeCode official this week would not say whether testing study patients for the marker could lead to a diagnostic intended to identify responders to the MI compound.
DeCode said it is not using the diabetes marker to test clinical trial patients even though it currently has drug research in that indication.
Illumina and DeCode penned their alliance after DeCode scientists and colleagues at various institutions in the United States published their findings concerning the link between LTA4H and heart attack risk in the January issue of Nature Genetics. In that article, the authors established an association between an LTA4H haplotype called HapK and heart attack with additional cardiovascular diseases in a study of about 2,400 subjects.
In cohort studies in the United States, the investigators linked this haplotype with a 16-percent increase in heart attack risk in white Americans and with a 250-percent increase in heart attack risk among black Americans.
According to a Celera Genomics spokesperson, the heart-attack risk test the company is developing will probably be its second molecular diagnostic, following a risk-assessment test in the company's pipeline for hepatitis C-related liver cirrhosis. It is not related to Celera Diagnostics' HCV viral-load and drug-susceptibility tests.
Celera's efforts to develop a test for risk of early heart attack hinge on the company's publication of a population-based clinical utility study that is currently in the works, David Speechly, a Celera spokesperson, told Pharmacogenomics Reporter this week. "We're talking months, not years," he said. "After publication, it is only a matter of time before a product is produced."
The two SNPs that the company this week said it hoped to add to the risk-assessment test resulted from a previous study of more than 2,000 subjects that currently appears online in the journal Arteriosclerosis, Thrombosis and Vascular Biology. The study will appear in print in the July issue.
Celera has for several years been developing a genotyping-based diagnostic to determine early heart-attack risk. The test is based on data from gene-association studies Celera Diagnostics has performed in partnerships with Bristol-Myers Squibb and several other collaborators. Celera Diagnostics was a 50-50 joint venture between Celera Genomics and Applied Biosystems until ABI sold its share of the JV to Celera Genomics in January.
The genetic risk assessment score diagnostic benefits from data produced by a second project the company is conducting to identify patients best suited to the statin class of anticoagulant drugs, said Speechly. Although the genetic risk score test might be used by physicians to guide their prescription of statins, it is intended to identify those who are in need of more aggressive preventative therapy in general.
The company hopes that if patients show greater-than-average genetic risks of heart attack, or a combination of genetic and environmental or concomitant health risks, they will be given more aggressive therapy, possibly including statins.
Asked what sort of product Celera's efforts would result in, Speechly said: "We need to be careful in terms of what we say right now around what the FDA is thinking, and what they're looking at. But we're working towards [a product], and we're working with the FDA to be sure that what we bring out is a product that Celera will anticipate to move towards commercialization."
The final result might take the form of a CLIA service or a stand-alone, FDA-cleared in vitro diagnostic product, but Speechly hinted at another possibility. "Instead of selling a test, we could work with a lab that [could] license the IP to those SNPs."
— Chris Womack ([email protected])