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Vermillion/Quest's OVA1 Ovarian Cancer Risk Test Cleared by FDA as IVDMIA


By Turna Ray

Following the 510(k) pre-market clearance of Vermillion and Quest Diagnostics' ovarian cancer detection test, the companies announced last week that the diagnostic would be available for physician use in the fourth quarter of this year.

The US Food and Drug Administration announced last week that it had cleared OVA1, a qualitative serum test that combines the results of five immunoassays using a proprietary algorithm to yield a single score indicating the likelihood that a woman's pelvic mass is malignant. The test is an in vitro diagnostic multivariate index assay, a complex subset of laboratory-developed tests the FDA has said it intends to regulate [see PGx Reporter 08-01-2007].

The clearance marks the agency's third approval of an IVDMIA, following that of Agendia's MammaPrint in 2007 and Pathwork Diagnostics' Tissue of Origin test in 2008. OVA1 is the first protein-based IVDMIA that the agency has cleared.

"OVA1 is the first FDA-cleared laboratory test that can indicate the likelihood of ovarian cancer with high sensitivity prior to biopsy or exploratory surgery, even if radiological test results fail to indicate malignancy," Vermillion said in a statement. According to the FDA, by detecting ovarian malignancies, OVA1 can help physicians determine what type of surgery to perform on a woman's pelvic mass.

OVA1 is indicated for women 18 years or older who have already been recommended for surgery due to their pelvic mass. The FDA specified that OVA1 should be used by primary care physicians or gynecologists as an adjunctive test. The test is meant to "complement, not replace, other diagnostic and clinical procedures," the agency noted.

The test "is not intended for ovarian cancer screening or for a definitive diagnosis of ovarian cancer," the FDA said. "Interpreting the test result requires knowledge of whether the woman is pre- or post-menopausal."

Furthermore, in the event that OVA1 results are negative, but results from other tests indicate cancer, "referral to an oncologist is appropriate," the FDA recommends.

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OVA1 was developed by Vermillion in collaboration with researchers from Johns Hopkins University. Quest, having invested an undisclosed sum in the research and development of the OVA1 technology, holds exclusive rights to offer the test to the clinical reference laboratory market in the US for three years.

Clinical Data

OVA1 gauges the presence of five biomarkers — transthyretin (TT or prealbumin), apolipoprotein A-1 (Apo A-1), beta2-microglobulin (Beta2M), transferrin (Tfr), and cancer antigen 125 (CA 125 II) — and employs its proprietary OvaCalc algorithm to determine the likelihood of malignancy in women with pelvic mass for whom surgery is planned.

The FDA cleared OVA1 based on the results of a prospective, double-blind clinical trial that involved 516 patients from 27 institutions where ovarian tumor subjects may undergo a gynecological examination. Of those patients enrolled in the trial, 269 were evaluated by non-gynecological oncologists, who compared OVA1 results with biopsy results.

Study results showed that when the OVA1 score was combined with pre-surgical information, such as radiography and information from other laboratory tests, physicians were able to identify additional patients who might benefit from an oncology referral, who were not previously identified using pre-surgical information alone.

"When combined with other clinical information, the OVA1 biomarker panel can help assess the likelihood of malignancy of an ovarian tumor before surgery and facilitate decisions about referral to a gynecologic oncologist," Frederick Ueland, principal investigator of the OVA1 clinical trial and associate professor of gynecologic oncology at the University of Kentucky's Markey Cancer Center, said in a statement.

At the International Gynecologic Cancer Society's 12th Biennial Meeting earlier this year, Vermillion presented data from a study analyzing the validity of OvaCalc, the proprietary algorithm used by OVA1 to gauge the risk of malignancy in pre- and post-menopausal women. The study, conducted by researchers from Johns Hopkins and Vermillion, showed that the OvaCalc algorithm detected 90 percent of stage I epithelial ovarian cancer cases and 100 percent of stage II to stage IV cancers. In the study, the algorithm maintained a negative predictive value of above 90 percent among both premenopausal and postmenopausal patients.

The National Cancer Institute estimates that only one third of women who undergo surgery for possible ovarian cancer are referred to specialist surgeons, as recommended by clinical practice guidelines. Previously reported studies show that patients with ovarian cancer live longer when their surgery is performed by gynecologic oncologists as opposed to general gynecologists or surgeons.

"Tests such as OVA1 personalize and improve public health by providing patients and health care providers with more information to support medical decisions that impact survival rates and reduce surgical complications," Jeffrey Shuren, acting director of the FDA’s Center for Devices and Radiological Health, said in a statement.

First to Market

OVA1 is the first FDA-cleared prognostic test for ovarian cancer in the pre- and post-surgical setting, according to Quest.

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Quest already provides CA-125 testing services for detecting residual disease in patients who have undergone first-line therapy and HE4 testing services for recurrence of epithelial ovarian cancer. The company, however, has been trying to develop and IVDMIA for ovarian cancer detection for several years now, and has faced regulatory challenges in its previous attempt at launching an IVDMIA in this space.

In 2002, Quest had inked a deal with Correlogic Systems and Laboratory Corporation of America for the development of an algorithm-based ovarian cancer detection test, called OvaCheck. However, two years later, the FDA sent a letter to Quest, Correlogic, and LabCorp, notifying that the OvaCheck test was an IVDMIA, possibly requiring pre-market approval.

Last year, a Correlogic spokesperson indicated the company has been in discussions with the FDA about OvaCheck and has "conducted extensive clinical trials on the test." At the time, the company said that it intended to submit the test for regulatory clearance [see PGx Reporter 09-03-2008].

Vermillion, for its part, has two other ovarian cancer tests under development in its pipeline. Its ovarian cancer high-risk triage test is simple blood test that may help doctors detect the disease in its earliest stages. Another prognostic ovarian cancer blood test being developed at the company aims to help patients and physicians make more informed treatment decisions.

According to the American Cancer Society, more than 22,000 women will be diagnosed with ovarian cancer this year, and more than 15,000 women will die as a result of the disease. Ovarian cancer accounts for approximately 3 percent of cancers in women.