NEW YORK (GenomeWeb) – Opko Health is hoping for a positive coverage decision from Medicare contractor Novitas as it continues to commercialize its 4Kscore test for prostate cancer.
The company noted during its Q4 2016 earnings call this month that it had expected Novitas to review the test during its February review cycle for draft local coverage determinations, but that the contractor had not yet announced LCDs for the 4Kscore or any other diagnostics in that cycle.
Novitas originally issued a positive LCD for the test in May of 2016 but withdrew this determination when Medicare contractor Palmetto issued a conflicting LCD that refused coverage of the test.
The 4Kscore uses levels of four kallikrein protein markers – total prostate specific antigen, free PSA, intact PSA, and hK2 – combined with patient age and digital rectal exam status to determine the likelihood of a patient having aggressive prostate cancer. Opko markets the test for use in patients either prior to biopsy or after a negative biopsy to determine their risk of aggressive disease.
The test, which is based on research initially performed at Sweden's University of Malmo, Finland's University of Turku, and New York's Memorial Sloan Kettering Cancer Center, is intended to tackle two significant challenges in prostate cancer diagnosis and management — overdiagnosis and the inability of biopsies to detect all cancers.
Overdiagnosis has emerged as a major issue in prostate cancer treatment. Men have their prostate-specific antigen levels tested regularly as part of standard clinical practice, but while a rising PSA can indicate cancer, in many cases it does not, and even when it does, the detected cancer is often slow-growing and presenting little risk. This means both unnecessary prostate biopsies and overtreatment of cancers found through these biopsies.
The 4Kscore test aims to tackle this issue by providing clinicians with a score assessing a patient's risk of having not just a cancer but an aggressive cancer that warrants a biopsy for detection and potentially subsequent treatment.
At the same time, the test looks to address the fact that biopsies can miss aggressive cancers due to the fact that they are examining only select portions of prostate tissue.
The company launched the test in Europe in 2012 through its partner International Health Technology and in the US in 2014 out of its Nashville, Tennessee-based CLIA lab. It later began offering the test through the network established by Elmwood Park, New Jersey-based clinical lab Bio-Reference Laboratories, which it purchased for $1.47 billion in 2015.
Contacted this week, Opko declined to provide 2016 sales figures for the test, but it previously noted on earnings calls that it performed around 14,500 tests in Q2, 16,000 in Q3, and that sales had seen "modest sequential quarter growth" from Q3 to Q4.
Steven Rubin, Opko's executive vice president, also noted on the company's Q4 call that it has obtained "a number of positive regional coverage decisions with commercial payers" and continues to "work with payers to secure favorable reimbursement" making "incremental progress."
Medicare would be perhaps the most significant of these, and Rubin said the company last year submitted "a complete clinical dossier to Novitas, which included background information, physician experience, and extensive clinical validation."
CEO Phillip Frost noted on the same call, though, that it was difficult for the company to get a sense of the timing regarding Novitas' reevaluation of the test.
Opko and collaborating researchers have published a number of studies in support of the test, including a clinical utility study published in Reviews in Urology in 2015.
However, in its negative LCD last year, Palmetto highlighted what it deemed a number of issues with the data supporting the test, including insufficient validation in the intended use population; changes to the test model; use of potentially inappropriate study subjects; and a lack of data assessing the value of the test prospectively in a well-defined patient population likely to be considered for biopsy.
In an interview this week, Eric Klein, chairman of the Glickman Urological & Kidney Institute at the Cleveland Clinic, said, however, that he believed the test "is one of the best-validated blood tests out there."
"There are tens of thousands of patients that this has been tested on in multiple different places," he added. "So I don't think you need to [further] validate its use."
The Cleveland Clinic began offering the test in 2015, relatively soon after it came on the market. Klein, who said he has no relationship with Opko, said he believed the test is most useful and best validated for use in patients who have had a prior negative biopsy but whose PSA levels are still rising.
"The issue is, when you biopsy a patient and it comes back negative, you can't be totally sure that you didn't miss a cancer because we know that biopsy is relatively inaccurate," he said. "It doesn't sample the whole prostate, and so if the PSA level continues to rise after that, you don't know whether you've missed a cancer or not. [The 4KScore] has been validated in that circumstance to be clinically useful."
That population represents a subset of the larger group to which Opko is marketing the test, which includes not just patients with negative biopsies and rising PSA levels, but also patients who have yet to undergo a biopsy.
Characterizing himself as a "liberal user" of the test, Klein said he orders it for around 50 patients a year. He added that better insurance coverage of the test would likely increase this number as some patients declined the test due to cost considerations. The test lists for $1,185, though Klein said for patients paying out of pocket, it only costs $395.
Opko said during its Q4 2016 call that despite not formally covering the test, Novitas was reimbursing the "majority" of 4Kscore tests submitted to it. Klein said, though, that most of his patients "have experienced at least some out-of-pocket expense."
Because of the overdiagnosis and overtreatment issues associated with prostate cancer, the disease has been a significant area of focus for the diagnostics community. Klein cited several other tests he viewed as competitors of the 4Kscore, including the Prostate Health Index, a protein test offered by Beckman Coulter; MDxHealth's PCR-based SelectMDx test; and Exosome Diagnostic's ExoDx Prostate test.
"My sense reading the literature is that all four of these tests perform at roughly the same level of accuracy," he said, though he had personal experience only with the PHI and 4Kscore tests.
He said the Cleveland Clinic's decision to offer the 4Kscore as opposed to the other tests was largely driven by convenience on the administrative side of things.
"It was the easiest for us to get up and running here at the clinic," he said. "It was easiest to get a process in place to order the test and have the patient [samples] drawn conveniently, and have convenient reporting. That's all. If you've got two tests that perform equally well biologically, and one's easy to order and get results on and one isn't, you go with the one that's easy."