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Vela Diagnostics Expects CE Mark Soon for NGS-Based HIV Drug Resistance Assay


NEW YORK (GenomeWeb) – Singapore-based Vela Diagnostics has developed a next-generation sequencing assay that detects and monitors resistance to HIV drugs, which could be available within Europe and other countries accepting the CE mark before the end of June.

The firm's Sentosa SQ HIV Genotyping Assay runs on its SQ301 next-generation sequencing platform, which is based on Thermo Fisher Scientific's Ion Torrent semiconductor sequencing technology. The test guides therapy in patients with a suboptimal virologic response or virologic failure while they are on first- or second-line regimens, Charlie Lee, head of R&D at Vela Diagnostics said.

Effective drug-resistance testing for HIV is especially important because the virus has an exceptionally high mutation rate, he said, adding that "there are over 200 drug resistance mutations to cover," leading to workflow requirements that make next-generation sequencing the most attractive option for this type of testing. 

Aiming to achieve clearance within the US, the firm has completed a pre-submission process with the US Food and Drug Administration, and it is "waiting for feedback" before applying for clearance to market the assay. Lee said that he expects that the US approval process could take six to eight months to complete, and in the meantime, the assay is being made available for use as a lab-developed test by laboratories with CLIA approvals.

By mid-2016, about 18.2 million people worldwide were receiving antiretroviral treatment. Some patients do well after starting treatment, because anti-HIV drugs drive down the viral load, but HIV's drug resistance can increase over time and viral load begins to grow again, Lee said.

For viral load testing, clinicians usually employ qPCR testing.

"Our NGS-based HIV Genotyping assay tests and monitors for drug resistance mutations in HIV after viral load is established," Lee said. "If the treatment is successful, the viral load can go down to a very low level, but as the viral load increases, you need to test again to understand which mutation is affecting drug resistance, and you can then precisely alter the drug."

Drug resistance testing keeps patients on drugs that are effective and gives them the best chance at suppressing the virus. It also helps cash-strapped, resource-limited healthcare systems and HIV programs to make cost-efficient decisions about which drugs are getting to which patients.

"Two million people worldwide contract HIV every year, and the World Health Organization's guidelines recommend that every single one of these infected individuals receives a drug resistance test on initiation of antiretroviral treatment," said Imogen Wright, co-founder and CSO at Hyrax Biosciences, which has launched a Web-based computational tool that provides low-cost HIV drug resistance testing to clinical researchers and accepts raw input data from any NGS platform. "This guideline is crucial to patient treatment outcomes and to transmission prevention. Next-generation sequencing can provide the automation required for large-scale drug resistance testing, and it is thus important that NGS-based tests become more broadly available and that a clear path to regulation exists for these tests."

It's important to manage HIV "right from the start, so that you reduce the risk of drug resistance and of having to go to a second line of treatment that costs more and has a greater burden for the patient and to the health system," Lee said.

Vela Diagnostics, founded in 2011, offers tests based on PCR and next-generation sequencing technologies. Early in 2015, the firm was subject to judicial management, a legal process similar to Chapter 11 bankruptcy, but rather than going out of business and liquidating its assets, a company under judicial management continues to operate under court supervision.

In August 2015, Vela Diagnostics and Luye Group signed an investment and collaboration agreement aimed at combining the benefits of diagnostics and drug development. Vela said in a statement at the time that the new investment would enable it to continue to invest in its PCR and NGS workflow innovations.

The firm's Sentosa HIV genotyping assay requires 730 microliters of a patient's plasma. Vela integrates its system for interpretation with drug resistance databases from Stanford University, REGA Institute at Katholieke Universiteit Leuven in Belgium, and the French National Agency for AIDS Research (ANRS), which consist of records of approved HIV drugs and associated gene mutations.

The turnaround time for the test is about 2.5 work days from sample to result, assuming an 8-hour work day, Vela said. The test requires 3.5 hours of hands-on time for loading samples, reagents, and consumables on the SX101 automated pipetting system; cleaning and setup for PCR processing on the ST401i instrument for sequencing template preparation and template enrichment; initializing the SQ301 sequencer; and loading the sequencing chip, Lee said.

In a collaborative study at the Ramathibodi Hospital Mahidol in Thailand, the system detected 33,439 drug-resistant mutations in 3,330 samples over 8 months. The samples consisted of reverse transcriptase, protease, and integrase proteins coded by the HIV DNA Polymerase gene.

In the study the system demonstrated clinical sensitivity of greater than 98 percent, and clinical specificity of greater than 99 percent, though these numbers will be finalized after the firm receives the CE mark, Lee said.

In a European clinical trial involving about 150 samples and performed in preparation for obtaining the CE mark, Vela used the TruGene HIV-1 Genotyping Kit and Sanger sequencing to compare results, he added.

Both NGS and traditional Sanger sequencing can be used to perform HIV drug-resistance testing, and both approaches are complementary, said Hyrax's Wright, adding that a potential advantage of NGS is that the quantity of data produced by the sequencing machines allows many HIV DNA samples to be analyzed concurrently, providing a large-scale workflow for drug-resistance testing.

"At the other end of the size spectrum, NGS is also rapidly becoming a portable technology, which will allow drug-resistance testing to be done at the point of care," Wright said, adding that there's a strong downward trend in cost for both Sanger and NGS.

Lee said that the price of the HIV drug-resistance test using Vela's technology will reflect the reimbursement landscape within the region or country in which it's being offered.