Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
For Vermillion, a Likely Off-Label Play for OVA1 as OVA2 Gains R&D Traction
This update includes a comment from a Quest spokesperson.
Vermillion released its first-quarter earnings report yesterday, and it came as no surprise that it remains in financial hot water.
And the steps it takes over the next several quarters will directly affect its partner Quest's position in the ovarian cancer triage-test market — not least because its chief rival, LabCorp, has repeatedly said it remains committed to re-launching its answer to OVA1, the OvaSure.
But it does have a handful of potentially lucrative tricks up its sleeve — one of which, admittedly, it has no control over. These include the likelihood that OB-GYNs will begin using OVA1 off-label as a screening test, which would sharply increase the market for the assay; launching a sister assay, OVA2, which is currently in development; and debuting a blood test to detect peripheral artery disease.
There has also been some talk about an OVA3 test, but details about it are more scarce than for OVA2. What is known is that OVA3 was mentioned as recently as March in a breakout session during a financial conference, according to two people who were present.
Vermillion and Quest, which will presumably market and perform these tests at its Chantilly Nichols Institute in Chantilly, Va., have also redoubled their efforts to win over additional payors to cover OVA1, and Vermillion has begun to consider selling the test in Japan, where the incidence of ovarian cancer has grown at twice the rate as in the US, according to people familiar with the companies' plans.
But first Vermillion must make its way out of the woods.
A quick recap: The company emerged from bankruptcy in January, four months after its sole bread winner, the OVA1 triage test, won FDA clearance. The test costs $650 and is reimbursed at $540 by Medicare, Vermillion has said. A company spokeswoman also told me Vermillion has "a contract with a private health plan," but would not name it.
Since launching the test in March and securing Medicare coverage for it "exceptionally quickly," in the words of one industry analyst, the company has sold only $73,000 worth of the test in the first quarter of 2010 — a far cry from the $9.7 million is expects to generate in sales of the test for the entire year.
More troubling, Vermillion has more than $290 million in accumulated deficit on its books since it went public a decade ago as a mass-spec vendor called Ciphergen Biosystems. And tools at its disposal for nibbling away at that debt include either raising cash — an option Vermillion has said it currently evaluating — and selling more OVA1s and developing and marketing additional assays.
"To become profitable, [Vermillion] may need to complete development of additional key diagnostic tests, obtain FDA approval, and successfully commercialize those products in addition to the OVA1 test," the company warned in an SEC filing last week.
One such test is its peripheral-artery disease assay, VASCLIR, which Vermillion has been co-developing with a team from Stanford University. In the SEC filing, Vermillion said "to date, Quest has selected only two diagnostic tests, which are … VASCLIR and the OVA1 test, to commercialize."
Vermillion has not said when it will be ready to submit VASCLIR for FDA approval.
But Vermillion has also been quietly working on another ovarian cancer test, called OVA2. The company spokesperson last month told me that "OVA2 and PAD are in our development pipeline," and said "details [will] come at a future time."
Vermillion has disclosed virtually nothing about OVA2, but people familiar with the company's thinking say the test could turn out to be a screening version of OVA1.
This strategy could simply formalize what may soon evolve organically. In interviews with OB-GYNs, I learned that some would order OVA1 for certain patients and would consider using it off-label to screen others, but would like to see additional studies that support their belief that the test can be used in this way.
In an e-mail, a Quest spokesperson said the company "is pleased with the rate of adoption and market acceptance of OVA1," and added that "we are marketing OVA1 in accordance with FDA clearance guidelines … and we expect that’s how physicians will use the test."
The two other steps Vermillion appears to be taking to eat away at its debt include nabbing additional payors and investigating other geographic markets for OVA1.
On the payor side, a person familiar with the company's strategy told me that as part of Vermillion and Quest's effort to secure more payors, they have divided the health-insurance market into big players and smaller players. Quest, with its vast reimbursement experience, is tackling the top-25 companies, while Vermillion chases the smaller fry.
In terms of peddling OVA1 to newer markets, Vermillion is apparently considering selling it in Japan, where the incidence of ovarian cancer in recent years has grown 10 percent. By comparison, the incidence in the US has increased 5 percent.
A person familiar with Vermillion and Quest's marketing strategy for Japan told me there could be "at least six" companies lining up to distribute the assay, which would be shipped to Quest to run.
Another potential OVA1 market is the UK, where Quest currently has a presence.