NEW YORK ─ Biocartis' recently announced collaboration with Lisbon, Portugal-based startup Ophiomics is focused on the launch of a prognostic gene expression test that identifies patients with hepatocellular carcinoma for curative-intent surgery and liver transplantation.
The firms intend to first appraise the appetite of European liver transplant centers for a manual version of the test, which they plan to launch as a CE-marked kit this quarter, and if the kit gains traction, they aim to jointly develop the test, called HepatoPredict, for use with Biocartis' fully automated, real-time PCR-based Idylla platform.
HepatoPredict, which according to Ophiomics has a total addressable market of about 50,000 tests per year, uses a needle biopsy to detect whether liver cancer patients are suitable for curative intent surgery and liver transplantation. The test uses a machine learning algorithm to provide a prognostic signature based on expression levels of four, undisclosed RNA biomarkers, morphologic information, and clinical criteria.
As part of the agreement with Ophiomics, Biocartis will initially distribute the manual kit, but if the firms decide to develop an automated version, the Mechelen, Belgium-based molecular diagnostics firm would play a broader role as codeveloper, contract manufacturer, and distributor, Erik Vossenaar, Biocartis' VP of business development, said in an interview.
The firms may also pursue regulatory clearances of the assay on the Idylla platform in Europe and with the US Food and Drug Administration, Vossenaar said.
The manual version employs a testing process that is standard for formalin-fixed paraffin-embedded-based manual tests, the firms said. It incorporates all reagents and protocols for RNA extraction from FFPE-needle biopsies, as well as for PCR and quality control.
By comparison, with Idylla-based FFPE tests, all assay steps are integrated in a single disposable cartridge, which Vossenaar said is "one of the unique features of the Idylla platform."
To automate HepatoPredict on the Idylla platform, the joint development team would automate assay steps such as deparaffinization and liquefaction of the FFPE samples, cell lysis, nucleic acid purification, and real-time PCR based amplification of the gene expression biomarkers. Biocartis said integrating the manual assay on the Idylla system is standard practice for its R&D staff who have developed a portfolio of complex assays on the platform, most of which are developed first to run tests using FFPE samples.
Both Ophiomics and Biocartis noted that making the test available on Biocartis' platform would enable broader use of HepatoPredict in molecular diagnostics laboratories, mainly because of the simplicity of its workflow.
The automated assay eliminates the potential for operator-induced variability and enables results in one to two hours compared to one to two days using the manual assay.
According to Ophiomics CEO Jose Leal, with the broader availability of an automated assay, more patients with hepatocellular carcinoma would be able to attend local hospitals for a needle biopsy and obtain results in the same day.
"With patients that are not eligible for a transplant, an alternative therapeutic approach can be determined as soon as the result of the test is available," he said.
Leal noted that the selection of hepatocellular carcinoma patients for liver transplant is currently based on clinicopathological criteria rather than molecular signatures and added that currently there are no in vitro diagnostic tests that compete with HepatoPredict.
Though liver transplantation is the only curative intervention for hepatocellular carcinoma, there is a limited number of donor livers for transplants, and patients need to be carefully selected for the procedure, Leal noted. HepatoPredict not only identifies patients with hepatocellular carcinoma who are most suitable for a liver transplant, but it also identifies patients who would otherwise be omitted as transplant candidates based on clinical criteria, he said.
In a recent study involving samples prospectively collected from patients at the Lisbon Liver Transplant Center, the HepatoPredict signature had a positive predictive value of 88.5 percent for about half of the patients recommended for a liver transplant and 94 percent for the rest of the patients recommended for liver transplant, Leal said, adding that Ophiomics has submitted the study for publication in an undisclosed, peer-reviewed journal.
"When we look at the data, our performance for patients who would normally be rejected for transplantation is better than for patients deemed eligible for transplantation under current criteria," Leal said, adding that about 30 percent of the patients selected for a transplant in the recent study were outside standard eligibility criteria.
Additional validation studies are ongoing, and within two months, Ophiomics expects to have tested about 500 patients overall in retrospective clinical evaluations.
Retrospective clinical studies involving US patients are expected to kick off later this year, and HepatoPredict is currently being validated in a prospective clinical study at the Centro Hospitalar Universitário de Lisboa Central in Lisbon where investigators are recruiting 40 patients with hepatocellular carcinoma related to cirrhosis who are candidates for liver transplantation.
Vossenaar said that Biocartis is implementing a collaboration model with other companies like the one with Ophiomics. It is using a comparable approach in a collaboration with Rotterdam, Netherlands-based SkylineDx to develop that firm's Merlin assay to predict a melanoma patient's risk of nodal metastasis, and with GeneproDx to develop an Idylla version of the GeneproDx ThyroidPrint assay.
Outside oncology, Biocartis' collaboration with Immunexpress to develop the SeptiCyte Rapid assay on the Idylla platform is similar to the approach it is employing with Ophiomics, and last November, Immunexpress obtained FDA clearance for the test, which distinguishes sepsis from noninfectious systemic inflammation in patients suspected of having sepsis.
"Like Ophiomics, numerous companies have developed promising biomarker tests, but they don't have the means to make them available to patients or market them to laboratories," Vossenaar said.
In its pursuit of future partners, the firm seeks companies that have "innovative biomarker assets and that are looking for routes to broadly commercialize these biomarker assets with the goal to jointly maximize patient access to innovative diagnostic tests," he said.
Its selection criteria include technical fit of the assay with the Biocartis MDx platform, market potential, and commercial fit, and in general Biocartis also aims to have complementary rather than overlapping assays on its platform and targets tests that appeal to its current customer base, Vossenaar said.