Decode Genetics plans to make a grand entrance into the diagnostics market, aiming to introduce as many as five new genetic tests for common diseases in 2007.
“We have several programs coming together to form a diagnostics franchise for Decode,” CEO Kari Stefansson said during a presentation at the JP Morgan Healthcare Conference in San Francisco on Jan. 11.
“We are taking advantage of the genetics that are coming out of discovery to develop DNA-based diagnostic tests. We expect to launch the first one in the second quarter of this year and follow with two to four additional tests this year.”
Decode plans to introduce these diagnostics initially as homebrew tests and then work with partner Illumina to launch FDA-approved diagnostic kits over the next few years.
Stefansson offered no updates on the company’s recent legal action against five former officials for allegedly stealing trade secrets in order to help kick-start the Center for Applied Genomics at the Children’s Hospital of Philadelphia, a “commercial enterprise competing directly with” Decode. The lawsuit, for which a trial resumed in November, is based on e-mails the former employees sent. Some of the emails appear to involve trade secrets for the very diagnostics programs that will feature prominently in the company’s future business plans [see PGx Reporter 10-04-06].
According to Stefansson, the company is investing the revenue from its more traditional capacities in genotyping, medicine, and chemistry services to support its entry into the molecular diagnostics business, an industry projected to be worth well over $1 billion by 2010. Decode is diving headfirst for that pot of gold by introducing diagnostics in therapeutic areas with a widespread public health impact.
“There are approximately 900 [genetic] tests available currently but they are all for rare, single-gene diseases,” Stefansson said. “The challenge in developing genetic tests for common diseases is that they must be based on variants with a large effect on many populations, and the lack of such variants being discovered has precluded development of tests for common diseases.”
However, the Icelandic genetics firm has taken on that challenge by isolating several of these variants for diseases that carry a broad healthcare burden, such as diabetes, atrial fibrillation and stroke, prostate cancer, myocardial infarction, and breast cancer.
The first test Decode plans to launch in the second quarter of 2007 is a homebrew test for variants in the TCF7L2 gene, which confers the risk of type 2 diabetes. According to Stefansson, the TCF7L2 polymorphism is the first variant discovered “with significant effect on type 2 diabetes [that] has been replicated in a very large number of populations across the world.”
The TCF7L2 variant is versatile, with the ability to predict patients’ risk of type 2 diabetes, their response to treatment measures, and their likelihood of developing insulin resistance based on poor insulin secretion, Stefansson said.
“What is interesting about this is that there are many groups that have done genotype scans with Illumina technology and Affymetrix technology in type 2 diabetes and the marker that always stands out …is the TCF7L2 [variant],” Stefansson said. “If you look at people who have abnormal glucose tolerance test without having full-fledged type 2 diabetes, if you have this at-risk variant, you have a larger probability of converting from just abnormal glucose tolerance to type 2 diabetes, than without this variant.”
In clinical trials, patients followed for two years had a 30-percent chance of converting from abnormal glucose tolerance into a full-fledged diabetic if they had the TCF7L2 variant. Without the variant, patients had a 20-percent chance of becoming a diabetic. The same experiment extended over four years increases the risk of diabetes to 30 percent for those without and to 50 percent for those with the variant.
“If you then ask the question, ‘How do these people with and without the at-risk variant respond to measures to try to decrease the probability of conversion into type 2 diabetes?’ it is clear that patients with this variant respond much, much more positively … to measures to prevent conversion from pre-diabetes to diabetes,” Stefansson said.
Decode expects the test “to help physicians to determine relative lifetime risk for type 2 diabetes to facilitate earlier lifestyle changes; to identify pre-diabetics at highest risk for conversion to type 2 diabetes and who should be more aggressively managed with weight loss or medication; and to help to separate patients who have type 2 diabetes on the basis of insulin resistance or those who have it on the basis of poor insulin secretion,” he outlined.
Atrial Fibrillation and Stroke
In keeping with its aim to target common ailments and broad disease populations, the second test Decode will likely introduce this year will be for atrial fibrillation to identify patients’ risk of new or recurrent stroke.
There are approximately 700,000 strokes per year. “Atrial fibrillation predisposes patients to stroke and stroke is the most common cause for disability in Western society,” Stefansson said.
The test is based on a copy-number variant that increases the risk of atrial fibrillation from 40 percent to 160 percent. During the call, Decode did not identify the variant gene, but noted that the same marker is also a major risk factor for cardiogenic stroke.
According to the company, the test may lead to better identification of patients who are at risk of stroke, as well as those who should receive more aggressive preventive treatment.
“The challenge in developing genetic tests for common diseases is that they must be based on variants with a large effect on many populations, and the lack of such variants being discovered has precluded development of tests for common diseases.”
“One of the things we neurologists have always been concerned about is that the large proportion of strokes may be caused by transient, undiagnosed atrial fibrillation,” Stefansson explained. “The trend today is to leave patients on monitoring not for 24 hours … but up to 72 or 96 hours to try to pick up brief episodes of atrial fibrillation.”
Stefansson noted that such lengthy monitoring measures have turned out to be “not terribly productive. So, it’s extremely important to be able to identify individuals who are up to four times more likely to develop atrial fibrillation than the population in general.”
Prevention of stroke is important since once it has occurred, patients have little possibility for recovery, he said, adding that he expects this test to be “widely and quickly accepted.”
Decode’s Growing Business
Stefansson noted that the forthcoming launches for Decode’s tests will be “prioritized according to market.”
While initially the diagnostics will be introduced as reference laboratory tests, Decode is simultaneously co-developing diagnostic kits with Illumina. The first diagnostic kit is slated for introduction in 2008.
“In an attempt to put together a diagnostic franchise, we’re making discoveries at a faster rate than we have ever done before since we started to use the Illumina technology,” Stefansson said. Some of the other impending diagnostics will test chromosome 8q markers for prostate cancer, in myocardial infarction testing for the leukotriene A4 hydrolase gene, and in breast cancer testing for the BARD1 gene.
In addition, the company is also in various stages of clinical development for several targeted therapeutics to prevent arterial thrombosis and heart attack, to name a few. It was not clear whether these therapeutics will utilize Decode’s upcoming diagnostics as companion products. Decode did not return follow-up calls prior to deadline.
The company recently completed a dose-ranging Phase IIa study for DG041, an anti-platelet compound for prevention of arterial thrombosis. In the study, researchers used safety and efficacy biomarkers related to atherosclerosis. Data from the trial is slated for release in the second quarter of this year.
Last fall, Decode suspended Phase III studies for DG031, an investigational agent for heart attack prevention targeting the leukotriene pathway, due to tablet dissolution issues. However, Stefansson said that Decode expects “to have taken care of this problem” by the end of this year and plans to restart the Phase III trial toward the end of this year or the beginning of 2008.
In the meantime, Decode has reexamined the drug’s pharmacokinetic and pharmacodynamic parameters and anticipates to be able to dose the drug once daily. “So it turns out that this drug after this little hibernation will come out a better drug than it was before,” Stefansson said.