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Population Genetics Technologies to Open US Space, Aims for 2016 Launch of FDA-cleared HIV Dx

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NEW YORK (GenomeWeb) – UK-based Population Genetics Technologies, which is developing infectious disease diagnostics, is opening up offices in Cleveland as it readies its HIV drug resistance and tropism test for launch in 2016 as a US Food and Drug Administration 510(k)-cleared and CE-marked product.

The HIV test is the first of several next-generation sequencing-based infectious disease tests the company plans to develop, with a hepatitis C virus test following close behind, PGT CEO Alan Schafer told GenomeWeb.

PGT's Cleveland operations will be based in the Baker Electric Building in the health-tech corridor of Cleveland. The company chose to locate in Cleveland in part due to a clinical collaboration it has with Case Western University's Miguel Quiñones-Mateu. Working with Quiñones-Mateu, who is an assistant professor of pathology at CWRU and scientific director of the University Hospitals Translational Laboratory and runs a CLIA-certified laboratory, PGT will validate its HIV assay.

Schafer said that PGT is validating its test on both Illumina's MiSeqDx and Thermo Fisher Scientific's Ion PGM Dx platforms. Prior to launching the test as a cleared product, Schafer said that the company is also considering launching a research-use-only version of the kit, which would help to both "demonstrate the value" of the test and "generate revenue." He said the company does not plan to run the test as a laboratory-developed test.

The assay was developed in PGT's UK laboratory and it has been "locked down" and analytically validated. In conjunction with Quiñones-Mateu, as well as other clinical collaborators with CLIA-certified laboratories, PGT will clinically validate the test. Schafer noted, however, that the company is not looking to establish its own CLIA-certified laboratory in Cleveland.

PGT chose an HIV test as its first product because there is already precedence in the field. "Sequencing-based information for clinical use in determining drug resistance is well established," he said. For instance, Monogram Bioscience's Trofile tropism assay, which uses Sanger sequencing, is considered the gold standard in tropism testing.

More recently, groups have been turning to next-gen sequencing due to its increased resolution. Quest, for instance, runs a test combining both Sanger and NGS, reflexing to NGS if the Sanger portion detects the CCR5 co-receptor. And MOGeneDx offers an NGS-based HIV test called ResistDx to help clinicians identify the appropriate drug combination for patients. 

Schafer said that moving HIV tests from Sanger sequencing to NGS instruments will offer critical advantages. Sanger sequencing has a limit of detection of around 20 percent. But, there is clear evidence that mutations at lower allele frequencies are "predictive of developing drug resistance," according to Schafer. Allele frequencies at the 5 percent level influence drug sensitivity and some evidence suggests that frequencies as low as 1 percent or below have an impact.

PGT's HIV test, which it has named VeX-HIV, will make use of the firm's VeriTag technology and be able to detect mutations down to a 0.1 percent frequency, Schafer said.

VeriTag is a sample prep method that tags each molecule with a unique oligo. Following PCR and sequencing, the molecules are grouped by their tag, such that every read with the same tag should be exactly the same. This allows errors that were introduced in the PCR and sequencing steps to be corrected. Without the tagging approach, rare mutations would be indistinguishable from errors, Schafer said.

PGT previously licensed its VeriTag technology to Agilent, but it still owns exclusive rights to the technology for infectious disease applications.

The VeX-HIV assay will target four genes — one that is used to assess tropism, which determines a patient's eligibility for the drug maroviroc, and three in which known mutations confer resistance to various drugs. The assay covers "all the known regions where there are defined resistance mutations," Schafer said. Running it on the MiSeqDx platform will enable multiplexing of 48 samples.

The company has not settled on a price for the test, but Schafer said it would be competitive with existing tests. The test would compete with Sanger-based tests, but currently there are no NGS-based HIV tests available as a diagnostic kit, Schafer pointed out.

Quest and MOgeneDx each run their respective HIV assays as laboratory-developed tests and Schafer said that Quiñones-Mateu offers an NGS-based LDT for assessing drug resistance in HIV patients, but he is not aware of other groups offering NGS testing for that indication. "If we come in with a test with the features that we're talking about, I think people will gladly use that rather than develop their own," he said.

Next up for PGT will be a hepatitis C virus assay, Schafer said. That test will also make use of the VeriTag technology, and the company will also pursue CE-IVD and 510(k) clearance for that test, which will assess drug resistance mutations. He declined to elaborate further on the test or a potential timeline for marketing.

Further down the road, he said the company would look to develop tests in the microbial space, potentially testing for drug-resistant microbes. "We have some initial collaborations in that space, but have not ascertained what our focus will be," said Schafer.

He added that while that field is moving toward unbiased shotgun sequencing, to enable the discovery of an unsuspected bug in a sample, there are a lot of challenges to that approach as well, from sample prep through analysis. "One critical aspect in these complex mixtures is having high enough sensitivity to be able to distinguish between closely related strains," he said, which is one area in which PGT could use its VeriTag technology.

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