NEW YORK (360Dx) – Genomic Health announced plans last month to expand its roster of prostate cancer tests to three, with a new agreement to commercialize a technology called IsoPSA, initially developed by Cleveland Diagnostics.
Genomic Health gained broad exclusive global rights to IsoPSA under the agreement. The firm plans to bring at least one test to market, which will aim to predict which men with clinical signs of prostate cancer have a low risk of developing high-grade disease and can thus avoid a prostate biopsy. To that end, the company expects to begin clinical validation of the test in 2018 with a goal of providing initial access to customers in 2020.
In the meantime, several other tests — including molecular assays from MDxHealth and from Exosome Diagnostics (ExoDx) — are already being marketed for this niche, and when Genomic Health launches the IsoPSA assay it will likely compete with these other products.
In an email this week, Genomic Health stressed that it chose to adopt the Cleveland Diagnostics technology based on confidence that it meets or exceeds the performance of various other methods and test products.
"It is our goal to offer as many tests as we can to address unmet needs across the patient journey, whether that is through our own development or in partnership with others who meet our bar for clinical evidence," Fred Pla, Genomic Health's chief business and product development officer, said.
According to Genomic Health, its choice was informed by a comprehensive review of potential partners and technologies in this space, in which IsoPSA emerged as the "best-in-class option."
"We believe IsoPSA has comparable, if not better, performance to other similar tests in distinguishing prostate cancer from benign prostatic conditions," Pla said.
In part, the decision was supported by a Cleveland Clinic-led multi-center prospective trial, published in European Urology, which found that IsoPSA significantly improved diagnostic accuracy over standard PSA testing and could reduce false-positive biopsies by between 45 and 48 percent.
For detection of any cancer from biopsy, the IsoPSA assay had significantly better receiver operating characteristics, with an area under the curve (AUC) of 0.79 compared to total PSA's AUC of 0.61. The IsoPSA assay also outperformed the standard PSA test for detecting high-grade prostate cancer specifically with an AUC of 0.81 compared to 0.69.
"This technical accuracy and precision, combined with the potential for simple integration into the current workflow of any urology laboratory practice made Cleveland Diagnostics the ideal partner for us," Genomic Health said in an email.
Unlike the tests currently being marketed by MDxHealth and ExoDx, which involve molecular technologies, the Cleveland Diagnostics IsoPSA strategy is a simpler proteomic one, which relies on measuring the spectrum of structural changes, or isoforms, of complex PSA.
Researchers describe the test as a structure-based, rather than concentration-based, assay that agnostically interrogates the entire spectrum of structural changes of complex PSA.
Genomic Health now plans to confirm the findings of the Cleveland Clinic study in another multi-center trial, which is already underway and is expected to be completed in the first half of 2018. Additional efforts may also focus on reproducibility and other practical matters of test commercialization.
One reason so many companies may be targeting pre-biopsy prostate cancer risk prediction is that the information provided by the existing standard PSA test is not an especially high bar to clear. As a result, showing that a test can do better than standard PSA may be less important moving forward than distinguishing one assay from another.
For its part, MDx Health has reported that its SelectMDx test improved identification of men at risk for harboring aggressive prostate cancer with an AUC of 0.90 and a negative predictive value of 98 percent for clinically significant prostate cancer
And in a study in JAMA Oncology last year, Exosome Dx showed that its own ExoDx Prostate Intelliscore test could significantly improve upon current standards, raising the AUC for discriminating high-grade disease from low-grade from 0.63 to 0.73.
Aside from those tests, there are also various protein-based strategies, which, similar to IsoPSA, seek to improve on standard PSA analysis. These include Beckman Coulter's FDA-approved and NCCN-recommended Prostate Health Index and Opko Health's 4-K score.
A potential competitive advantage for Genomic Health, despite its timing being behind several other assays, is the company's existing sales channel and presence in the urology community.
Pla said that as a reflex test performed for any patients with PSA levels above two, the IsoPSA assay would be offered by physicians that are represented in Genomic Health's existing customer base of urologists and large urology group practices.
But other firms in the space have been marking significant commercial milestones. ExoDx announced at the end of November that the US Centers for Medicare and Medicaid Services had finalized a coverage price for its test at $760.
According to Exosome Diagnostics COO Tom McLain, about 50 percent of the patient base that would benefit from the company's test has Medicare for their primary insurance coverage. The firm has also begun evidence development efforts designed to drive coverage of the test by private payors.
For its part, MDx Health has focused mainly on the European market, signing numerous distribution deals for SelectMDx over the last year, most recently in Spain.
But a note of caution about these tests was raised in a recent commentary in European Urology that discussed the Cleveland Clinic's IsoPSA validation, Cedars-Sinai surgeons Devin Patel and Stephen Freedland wrote that despite the individual merits of various available tests, "the merits of one particular biomarker over any other remains unknown. Thus, while all of these biomarkers appear to 'work,' it is not known which one works best for which populations."
"Many biomarkers exist today and while all outperform PSA, they are not widely used for several possible reasons: (1) there are too many biomarkers, leading to confusion about the best biomarker; (2) the new biomarkers, while better than PSA, are still not good enough; and (3) there is a lack of high-quality comparative-effectiveness studies," Patel and Freedland wrote. "While we believe that all three are reasons for the limited use of these biomarkers in practice, the lack of comparative studies is a particular major limitation."