NEW YORK (GenomeWeb) – Although it was one of the first companies to develop methods for highly sensitive sequencing of circulating tumor DNA, Personal Genome Diagnostics has so far limited its liquid biopsy testing to the research market.
That changed last week, though, with the launch of the company's first clinical blood-based cancer sequencing test, PlasmaSelect 64 — a pan-cancer targeted next-gen sequencing assay that offers physicians the opportunity to look for actionable alterations in a patient's tumor without having to do an invasive biopsy.
Melody Gretz, PGDx's vice president of marketing, told GenomeWeb this week that the panel was designed to be just comprehensive enough to be informative for a wide variety of cancer types, while avoiding an overload of information that she argued can make an assay more trouble than it is worth to oncologists.
"Many oncologists are still trying to figure out what pan-cancer assays are and what to do with the result," she said, "so that's why [focusing only on things that are] clinically actionable is so important. We have to be able to tie the results to an action they can take."
Other companies in the liquid biopsy space have followed this logic even further, developing narrower panels that include only genes relevant to a single type of cancer rather than a pan-cancer panel. Examples include Resolution Biosciences, and more recently, Genomic Health and Inivata.
More direct competitors for PGDx's new test are firms like Guardant Health, which offers its own (currently 70-gene) pan-cancer assay Guardant360, and Foundation Medicine, which debuted its 62-gene FoundationAct in March.
PGDx believes PlasmaSelect 64 strikes a balance between comprehensiveness and clinical actionability with specific advantages over potential rivals.
For one, although its gene list overlaps significantly with those included in Guardant's and Foundation Medicine's tests, Gretz said that PlasmaSelect includes 15 unique biomarkers that PGDx claims are not included in any other NGS-based liquid biopsy assays.
PGDx CEO Douglas Ward said that that company has also paid special care to make the test accessible not only to physicians at the forefront of genomic medicine, but also oncologists in community and other settings that are less familiar with the field. To that end, the company worked hard to craft its reporting system in a way that not only describes the genomic findings but also what the options are for therapy or other clinical interventions that are associate with those findings.
According to PGDx, another important distinguisher for PlasmaSelect is the company's proprietary methods for DNA extraction, sample preparation, sequencing, and variant calling. These include its PARE (personalized analysis of rearranged ends) technology — licensed from Johns Hopkins last year — as well as what it calls "VariantDx" computational algorithms that help distinguish true mutations from sequencing artifacts and errors.
The question of sensitivity and accuracy of liquid biopsy assays, and transparency in communicating these factors to customers, was raised at a recent US Food and Drug Administration workshop.
PGDx hasn't published its validation data for PlasmaSelect 64 yet, but the research-use version of the panel has been used in clinical research collaborations and has yielded some data in that arena.
In 2015, the company shared data at the annual meeting of the American Association for Cancer Research from an evaluation of the RUO version of PlasmaSelect. The company performed dilution experiments using tumor-derived DNA with well-characterized somatic mutations in the presence of different concentrations of wild-type DNA.
According to the company, PlasmaSelect was able to detect genetic alterations with a limit of detection of 0.1 percent with high specificity.
And, in a recent proof-of-principal study with Takeda, researchers assessed a 63-gene version of PlasmaSelect in 12 patients — demonstrating that the blood-based analysis was concordant with sequencing DNA from a patient's tumor tissue.
Offered through PGDx's CLIA lab, PlasmaSelect 64 is a laboratory-developed test, but Ward said that the company's ultimate goal is developing IVDs.
"Without a doubt we are an IVD company, and that is [also] a key differentiator … combining the ability to offer clinical testing for early adopters and for pharma now [through PGDx's CLIA lab] but then also working toward a decentralized test that anyone can do."
Some of this IVD development will be fueled by pharma partners looking for companion diagnostics. For example, based on the positive results of their research, PGDx and Takeda are moving forward with a larger study using a more specific assay for non-small-cell lung cancer that PGDx custom designed.
Alternatively, PGDx could also develop bespoke panels outside of a CDx context where there is a clinical need for something more specific than the full PlasmaSelect 64.
According Ward, the firm is already in the process of taking one smaller panel through the FDA, though he did not provide further details on that test or its content.
Resolution Biosciences has also said that disseminated or decentralized test development is the central goal of its liquid biopsy business.