NEW YORK (GenomeWeb) – Vermillion announced this week that it has received US Food and Drug Administration 510(k) clearance for Overa, its second-generation proteomic test for pre-surgical assessment of the likely malignancy of ovarian adnexal masses.
The test offers several improvements over the company's current lead product OVA1, which in the half decade since its launch has gained little traction in the marketplace.
Vermillion this month published a clinical study detailing Overa's performance in the American Journal of Obstetrics and Gynecology and now plans to begin offering the test through an early-access program designed to generate additional performance, outcome, and health economic data, Vermillion President and CEO Valerie Palmieri said on a conference call this week following release of the company's Q4 and full-year 2015 earnings results.
One of the key areas in which Overa improves upon OVA1 is specificity and positive predictive value, which have proven a stumbling block for the first-generation test. In the AJOG study, the test distinguished between benign and malignant masses with specificity of 69 percent and positive predictive value of 40 percent, compared to 54 percent specificity and PPV of 31 percent for OVA1.
The sensitivity and negative predictive value of the two tests, meanwhile, were equivalent.
"We had very strong negative predictive value with OVA1, but marginal positive predictive value, and now we have a test that has both," Palmieri said on this week's call.
As Laura Havrilesky, a gynecologic oncologist at Duke University, explained to GenomeWeb in a 2011 interview, low specificity was an issue for OVA1 in that it meant the test was identifying likely benign patients as likely malignant, which, in turn, meant Ob-Gyns were passing patients on to gynecologic oncologists for surgeries that they could have done themselves.
"Looking at those [specificity] numbers, if you were sitting in your general Ob-Gyn practice, they might be a little concerning – 'A lot of my benign cases are going to go out the door because I'm doing this test on everybody,'" she said.
Another area in which Overa improves over OVA1 is by eliminating the need for doctors to assess a patient's menopausal status. OVA1 uses different cut-offs for pre- and post-menopausal women, which, Donald Munroe, Vermillion's chief scientific officer, said had been an issue with some doctors concerned about using the test in patients with ambiguous menopausal status.
Additionally, Munroe noted that the test, which replaces two of the five OVA1 biomarkers with HE4 and FSH, was designed to run on a single, integrated platform, the Roche Cobas 6000. This is in contrast to OVA1, which ran on two different platforms. Munroe suggested that the move to the Roche platform would help with international clients and large reference labs.
Palmieri said Vermillion has applied for a Category 1 Current Procedural Terminology code from the American Medical Association for Overa and launched an early-access program, through which institutions can begin using the test. According to Munroe, Vermillion will select early-access users based on a variety of criteria, including "their commercial appeal, institutional prestige, and commitment to accelerating clinical utility publications and local guidelines."
Munroe added that Vermillion plans to submit around six publications on the test to peer-reviewed journals this year.
As the company rolls out Overa, it is also working to boost OVA1 sales, which were down 19 percent in 2015 to 13,598 from 16,839 in 2014. Of the 13,598 tests performed in 2015, 8,937 were done by Quest and 4,661 were performed by Vermillion's Aspira Labs subsidiary. The company attributed the decline in volume to the process of transferring testing from Quest to Aspira, with Eric Schoen, the company's chief account officer, noting that as a new billing entity separate from Quest, the company was experiencing claim denials and delays on tests.
"The payor contracts did not come over with the Quest specimens, so Aspira is in the process of obtaining its own payor contracts," he said, adding that this would affect the timing with which Vermillion recognized test revenue.
The company ended its licensing agreement with Quest as part of a plan to improve its fortunes by bringing sales in house to gain better control of the process. Management believed that, as just one test in Quest's large catalog of offerings, OVA1 was not consistently getting the attention and support needed to drive adoption of such a new, highly complex diagnostic.
Increased attention to its own internal sales efforts, including a tripling of its internal sales staff in 2014, did little to drive sales of OVA1, however. And, in fact, on this week's earnings call, Palmieri indicated that Vermillion was moving again to outsource some of its sales operations, looking to external sales forces and agreements with large regional reference laboratories.
"We are in late-stage discussions with several [reference labs], and an agreement is eminent," she said. She noted, however, that the company was "not looking to repeat Quest."
"We want to make sure that we are with a consultative sales force. We want to make sure that we are getting the proper traction and are with the right players," she said, adding that as part of such an arrangement the company will "implement specialized training programs" for their partners.
Vermillion currently has 11 internal salespeople who Palmieri said are focused on markets where the company has strong support from key opinion leaders and positive medical coverage. She said it plans this year to add to its sales force, either internally or externally.
Vermillion is also continuing work to establish its pelvic mass registry, which is key to its plans to expand its tests into additional conditions and intended uses. According to Munroe, the company has finalized a study protocol under which it will follow women from the initial identification of a pelvic mass through surgery, diagnosis, and 12-month follow up. It plans to enroll its first patient in the third quarter and have at least 100 patients enrolled by the year's end, he said.
The registry figures in the latest of Vermillion's initiatives, the effort, which Palmieri announced on this week's earnings call, to offer research services out of Aspira with the ultimate aim of moving into the companion diagnostics business. She declined to go into specifics, noting that it was still early days for the effort, but said the company believed it could leverage its expertise and clinical assets such as the registry, which Vermillion expects will enable research into a range of gynecologic conditions, to gain a foothold in this space.