A blood test being developed by Yale University and Laboratory Corporation of America to detect early-stage ovarian cancer could generate significant tech-transfer revenues for the university if LabCorp can turn it into a routine test akin to mammography or a Pap smear.
According to Yale and LabCorp, Phase II data show that the six-protein-biomarker blood test can detect ovarian cancer at any stage with 99.4-percent specificity and 95.3-percent sensitivity — which would make it the most specific and sensitive test of its kind to date, according to the researchers.
The test, currently in Phase III trials, is based on the multiplexed detection of six protein biomarkers discovered by a team led by Gil Mor, an associate professor of reproductive sciences at the Yale School of Medicine, and colleagues.
In 2006, LabCorp exclusively licensed the biomarker panel and testing method to develop a diagnostic for epithelial ovarian cancer. Under the agreement, Yale received an undisclosed signing fee, and will receive undisclosed milestone payments and royalties on future products. It’s the university’s first deal with the reference lab.
“When we first published this suite of biomarkers, we marketed this to a number of companies,” John Puziss, director of technology licensing at the Yale University Office of Cooperative Research, this week told BTW. “After having gone through offers from several other major diagnostic manufacturers, we moved forward with LabCorp. It was the most attractive deal and they seemed to be the most serious about developing the product.”
Specifically, Puziss said that LabCorp agreed to “very stringent” due diligence provisions, “which are particularly important to us. We wanted to be sure that whoever licensed this was going to be really focusing a lot of time, effort, and money on developing a product based on the technology, and not just sitting on it.”
Puziss also cited LabCorp’s experience in developing both nucleic acid- and serum-based tests. “They have both a reference lab and the interest and ability to develop, basically, an [in vitro diagnostic] point-of-care test,” Puziss said.
Specific financial terms of the agreement were not disclosed, and both Yale and LabCorp officials this week declined to provide additional details.
A spokesperson for LabCorp told BTW that the firm has entered into sponsored research and licensing deals with several universities and non-profit research institutes in recent years, and has developed ongoing relationships with many of them.
The most recent and notable of these relationships is with Duke University, from whom LabCorp licensed a blood-based assay for early detection of lung cancer earlier this year. In 2006, LabCorp also partnered with Duke to create the "Duke-LabCorp Scholars in Genomic Medicine" program to support research studies on genomic-based clinical testing.
‘Not Specific Enough’
In the Phase II study of the ovarian cancer test, published earlier this month in Clinical Cancer Research, Mor and colleagues presented the results of an analysis of the proteins leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125. The study comprised samples from 156 newly diagnosed ovarian cancer patients and 362 controls.
The researchers determined protein concentrations using a multiplexed, bead-based immunoassay based on Luminex technology, and found that the test had a sensitivity of 95.3 percent and a specificity of 99.4 percent — better than any other presently available test, they wrote.
“After having gone through offers from several other major diagnostic manufacturers, we moved forward with LabCorp. It was the most attractive deal and they seemed to be the most serious about developing the product.”
However, in an earlier study they conceded that “due to the low prevalence of ovarian cancer in the general population, it could be argued that it is not specific enough as a clinical test for ovarian cancer detection. In order to outweigh the benefit of early detection with the complication of surgery for false-positive screening results, an ovarian cancer screening strategy must achieve a minimum of 99.6 percent specificity.”
In an interview this week with BTW sister publication ProteoMonitor, Mor said that the test stands out among others because it is the first to be validated in a second round of testing.
“The publication … is [a] validation and an improvement of the test that we reported in 2005,” Mor said, referring to a diagnostic based on four protein biomarkers. “There are many papers [in which the authors] publish once and they never come back with a validation.
“I think we really are the first ones who have a second publication following a validation of the first discovery,” Mor added. “[Another difference] … is that in this report, we [also] did a discovery phase and then a blind clinical trial [for] the test, and in that blind study, we obtained that sensitivity and specificity.”
Mor also said that some of the biomarkers that comprise the panel are not proteins that are produced by the tumor, which differs from current thinking that cancer biomarkers must be proteins produced by the tumor.
“That is true when you have a tumor that is in late stages of disease, or when you have a big mass in stage III or IV,” Mor said. “It produces so much tumor protein that you easily detect [them] in the blood.”
However, for detecting ovarian cancer in its earliest stages — which is crucial due to the high mortality rate associated with later stages — Mor said that the elevated presence of innate proteins can also be a telltale.
“In the early stages of a tumor, it’s like a little baby,” he said. “It’s just a little group of cells, and what it produces is very low, and in many cases [is] undetectable in the blood. However, the [tissue] surrounding the tumor … recognizes the presence of those malignant cells. And that response can be detected in the blood.”
Mor added that his research group has determined that six protein biomarkers seems to be optimal. “The thinking was that maybe adding more proteins would increase the sensitivity. We went through a lot of proteins, a panel of 10, and that didn’t help. And the reason is there is a lot of variation between patients. What we tried to do was create a specific profile for ovarian cancer.”
According to LabCorp, ovarian cancer is the fifth-leading cause of cancer-related deaths in US women. Despite being one-tenth as common as breast cancer, its mortality rate is three times higher. This year, approximately 20,180 women will be diagnosed with the disease, and 15,310 will die from it.
If LabCorp and Yale can gain regulatory clearance for the test and bring it to market, its creators envision that it will become a regular part of a routine medical examination.
“The vision … for this test is that it could be given once a year during an annual well-patient visit to their Ob-Gyn, and it’s just a simple blood test,” Puziss said. “You’re looking for the presence of markers [that] together have 99-percent accuracy in diagnosing very-early-stage ovarian cancer.
“So the patient goes in, they draw a little blood, they run the test, and if the markers come up they can catch this at potentially a much earlier stage than it is currently, and it’s therefore much more treatable,” Puziss added. “It could save thousands of lives.”