Diagnostic startup Exagen is betting that a technology platform it developed that can identify much smaller sets of genetic markers than its competitors will give it a head start in the race to bring in vitro diagnostic multivariate index assays to market.
The Albuquerque, NM-based company plans to file its first diagnostic, for breast cancer recurrence, with the US Food and Drug Administration as an IVDMIA within the next two months.
The test would be the fourth genomic-based breast cancer assay to hit the market after similar diagnostics from Genomic Health, Agendia, and Quest Diagnostics. However, Exagen officials are confident that the computational approach it used to develop the test will give it an edge over the front-runners in the field.
The test would fall into a category of products the US Food and Drug Administration described in a draft guidance last fall and discussed in a public meeting last week [see related article, this issue].
These tests, IVDMIAs, use mathematical formulas to interpret gene and protein data to guide medical decision-making. In its draft guidance, the FDA said they must be cleared by the agency; ordinarily they would be overseen by Clinical Laboratory Improvement Amendments regulations.
According to Exagen, its software doesn’t select a set of predictive genes from a gene-expression data set based on ranking alone, as other tests might. Rather, its platform, called the Exagen Discovery Engine, iteratively evaluates the predictive power of gene combinations to determine which combinations best discriminate between two patient types, regardless of the predictive power of the individual genes on their own. A typical search can include up to 50,000 iterations, the company said.
Exagen claims that this platform enables it to discover a set of biomarkers and develop a diagnostic test within two months, compared to two to three years for other firms.
According to the company, this approach also allows it to identify much smaller sets of genes than its competitors — between three and five genes, as opposed to 21 genes for Genomic Health’s Oncotype Dx and 70 genes for Agendia’s MammaPrint.
In addition, Exagen claims that the predictive accuracy of these smaller gene sets is much higher than that of its rivals because it accounts for those genes that would otherwise not meet the threshold for a ranked gene list, but might provide very high predictive accuracy in combination with other genes.
The primary advantage of a three-gene biomarker panel, according to Exagen, is that it enables the firm to package and license the sets as reagents to large commercial testing laboratories, which can then run the assays using any standard fluorescent in situ hybridization platform.
Genomic Health and Agendia “have a high number of genes, so they have to do the testing themselves” as CLIA-certified laboratories, James McClintic, CEO of Exagen, told PGx Reporter sister publication BioInform this week. Genomic Health uses RT-PCR to analyze the 21 genes for Oncotype DX, while Agendia uses custom Agilent microarrays for its 70-gene panel.
“We’re able to get the same answer with fewer genes, so we can put this in a kit and sell it to reference laboratories,” McClintic said. “So where they are a reference laboratory and a service provider, we are a discoverer, developer, manufacturer, and distributor of kits.”
Exagen expects this business model to give it broader market reach because it can team with well-established reference labs rather than tackle the market on its own. Under this strategy, it must file for 510(k) clearance from the FDA, but that’s a requirement that the company welcomes — especially in light of recent developments at the FDA regarding multi-gene tests (see related stories, here and here).
Can Genomic Health Compete?
During a presentation this week at the Biotechnology Industry Organization’s CEO and Investor conference in New York, Genomic Health President Kim Popovits said that the company was looking to expand Oncotype DX’s market into single-gene reporting and into node-positive patients.
Oncotype DX is indicated for patients who have early-stage breast cancer, are taking tamoxifen, and are estrogen receptor-positive and node-negative.
“In 2007, we want to expand the Oncotype DX assay,” Popovits said.
She said that the company was focusing on the Oncotype DX and single-gene reporting at the growing request of oncologists who have indicated they would like to know the individual gene scores for ER and PR.
“We’re able to get the same answer with fewer genes, so we can put this in a kit and sell it to reference laboratories.”
“We also want to do studies in our node-positive patients,” Popovits said. “There is clinical belief that the test would work in node-positive women,” a market which could potentially add another 65,000 women within Genomic Health’s reach.
“That would be a significant market expansion for us, so we’re beginning work in the node-positive population,” Popovits said. However, she added that she didn’t think the company was “near peak sales in terms of our ability to expand the usage [of Oncotype DX] into other patient populations within the breast cancer group.
“So you’re looking at a lifecycle that is longer than many would have thought it would be, looking at typically what the diagnostic industry is like,” she said.
IVDMIA Guidance Works For Exagen
Exagen’s McClintic, who spoke to Pharmacogenomics Reporter sister publication BioInform from the FDA’s IVDMIA public meeting in Gaithersburg, Md., on Thursday, acknowledged that his firm is clearly a minority in the genomic diagnostic industry in its support for the draft guidance.
“There have been 20 speakers already and the majority of them are dead set against any kind of regulation,” McClintic said. “Nobody likes regulation, but we spoke entirely for it because it fits our business model like a glove. Everything that was in that FDA guidance, we were already doing.”
He noted that the FDA clearance of Agendia’s MammaPrint should help Exagen by clearing a path through the regulatory agency for future IVDMIAs. “They did some groundwork for us and that’s going to probably trim about 60 days off of our process because they’ve done it and they’ve now become the predicate device,” McClintic said.
“For a company like [Exagen], these guidelines are good because we know how to build the tests with very few bets,” McClintic said.
He noted that with the exception of Agendia, which still offers MammaPrint as a service from its lab in Amsterdam rather than marketing it directly to reference labs, “we don’t think that there is going to be any other competition [regarding FDA-approved IVDMIAs] for quite awhile.”
McClintic said that Exagen plans to file its breast cancer test with the FDA within 60 days. After that, he said the company has two tests for inflammatory bowel disease and a second breast cancer test in the pipeline that should be in clinical trials in the first half of the year.
Pharmacogenomics Reporter editor Turna Ray contributed to this article.
A version of this article previously appeared in PGx Reporter sister publication BioInform.