Most companies exploring liquid biopsies use technologies that search for and sequence DNA strands shed by tumours into a patient’s blood. Not so Menarini Silicon Biosystems: the company offers Cellsearch, the only FDA-cleared product for the enumeration of entire circulating tumour cells (CTCs) in blood samples.
“With CTCs we can offer a wide range of information compared to circulating tumour DNA [ctDNA],” Fabio Piazzalunga, president of MSB, tells Vantage. “We believe that the future will be linked to single-cell technologies.”
Single cell analysis is a technique that can aid the understanding of metastasis and therapy resistance with more precision than bulk tumour measurements, as well as tease out the role of rare cells in tumour progression. MSB’s Cellsearch technology can perform this testing; the company, a subsidiary of the private Italian pharma company Menarini, bought Cellsearch from Janssen in 2017.
Cellsearch can obtain clinically useful information in a number of ways. Most obvious is simply counting the cells, which can be used as a prognostic marker in metastatic disease, and it is this use for which Cellsearch has FDA clearance, as a way to monitor patients with metastatic breast, colorectal or prostate cancer.
It also has other potential applications for which it is not yet approved. These include measuring tumour antigens such as Her2 and PD-L1, useful for selecting targeted drugs or immunotherapy and monitoring the effectiveness of the treatment, and, based on the analysis of a single cell, acquire “information on tumour heterogeneity and chronicle how its evolution responds to therapy”, Mr Piazzalunga says. The CTCs can be isolated as live cells, providing information on gene expression.
The group is not entirely eschewing the other liquid biopsy approach, however. It has a distribution agreement with the Taiwanese company Plexbio under which it distributes the latter's IntelliPlex circulating tumour DNA analysis technology.
“We believe that the two technologies, CTCs and ctDNA, provide complementary rather than mutually exclusive information,” Mr Piazzalunga says.
MSB is not pursuing new regulatory clearances at the moment. Instead it is developing new uses for its systems; Mr Piazzalunga says it is working towards a new application of the Cellsearch technology related to multiple myeloma.
The system can run a full battery of tests, including the in-depth analyses that are not yet approved by the regulators, on around five patient samples per day, Mr Piazzalunga says. He adds that the company is working towards upgrading the system to allow a shorter turnaround time.
MSB is also moving into another fast-growing area: prenatal testing. Remarkably, cells can pass from a foetus into the mother’s bloodstream, and MSB is working towards developing tests for foetal genetic disorders using a blood draw taken from the mother. The technology will be able to detect several prenatal abnormalities, though Mr Piazzalunga declined to specify exactly what these might be.
The prenatal diagnostic will be a laboratory-developed test sold under a Clia waiver “at the beginning”, Mr Piazzalunga says. “Once we get the necessary clinical evaluation data, we will submit it.”
Too many companies
But liquid biopsy is the big prize. As targeted therapies and immuno-oncology continue their meteoric rise, competition to develop a successful blood-based test to aid patient selection is fierce, and companies are increasingly vying to have their tests put on an equal footing with tissue biopsy (Esmo 2019 – Foundation eyes liquid biopsy rule change, September 30, 2019).
“There are many, many companies in the liquid biopsy space – we believe there are too many,” says Mr Piazzalunga, not unreasonably. He believes that the market will come to a crunch point after which the less successful cancer blood test developers fall by the wayside. After that, he says, a couple of dozen test makers will remain, “and we count on being one of those”.
Having FDA clearance for a cell-counting test in three metastatic, solid tumour indications is a commercial advantage, Mr Piazzalunga says. Tests such as Foundation Medicine’s FoundationOne Liquid and Guardant Health’s Guardant360, both of which use circulating DNA rather than CTCs, are on sale in the US as lab-developed tests but are not approved or cleared by regulators.
At least one other company is also looking at CTCs: the UK-based group Angle (Interview – Aiming for a new Angle on liquid biopsy, July 25, 2017).
MSB will not disclose its sales, though Mr Piazzalunga says it is “by far the market leader” in CTC, with more 45,000 CTC tests run per year. By contrast Guardant360 is forecast to have sales of $185m in 2019 – and should Guardant’s test gain the FDA’s imprimatur too, it will likely see a bit of a sales boost.
Competition is only getting more intense, and doctors will only be convinced of the utility of cell-based tests by positive clinical data. It is data that will determine whether MSB ends up as one of the last groups standing.