UK study supports clinical uptake of Genedrive newborn hearing loss test in the NHS

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NEW YORK — A recent study in the United Kingdom will lend support to the widespread adoption of a point-of-care pharmacogenomic test in that country that could spare newborn babies the potential hearing loss associated with a widely prescribed antibiotic.

The point-of-care test and device, manufactured by Genedrive, based in Manchester, UK, was implemented in a trial in cooperation with partners based at Manchester University NHS Foundation Trust. The study, called Pharmacogenetics to Prevent Hearing Loss, or PALOH, was funded by a £900,000 ($1.2 million) grant from the UK’s National Institute for Health Research and took place from January to November 2020. Its results were published last month in JAMA Pediatrics.

The effort recruited 751 babies from two units within the trust who were screened for MT-RNR1 m.1555A>G, a variant that predisposes carriers to hearing loss when prescribed the antibiotic gentamicin broad-spectrum first-line given to neonates admitted to intensive care units. Around 1 in 500 people carry the variant and around 100,000 newborn babies are admitted to ICUs in the UK each year, 80-90% of whom will be treated with gentamicin. Not only did Genedrive’s test work well in the study, but investigators were able to identify three babies who carried the mutation and were at risk of lifelong hearing loss if they prescribed the drug.

Bill Newman, consultant in genomic medicine at Manchester University NHS Foundation Trust and corresponding author, said the study demonstrated both the utility of the Genedrive test, as well as its ease of adoption in an acute setting.

“The key for us was to show that the introduction of this technology did not delay the routine prescription of antibiotics,” Newman said, noting that decisions about administering antibiotics must be made within an hour. admission to an intensive care unit. “You can have the best test in the world, the best technology in the world, but if it doesn’t fit into the clinical pathway, it’s not useful,” he said.

The study showed babies were still prescribed antibiotics in the same amount of time as they would be without the use of the test, he said, demonstrating that adding genetic testing as part of intensive care did not slow down decision-making.

“I think that was one of the main learning points for us,” he said. “Integration of the test into normal routine clinical pathways was absolutely essential for its adoption.”

Genedrive’s MT-RNR1 Identification Kit is a in vitro molecular assay for use on human buccal cells. The test relies on an isothermal amplification approach mediated by a reverse transcription loop to produce a result in approximately 26 minutes. Genedrive originally relied on RT-PCR for testing, but switched to RT-LAMP to reduce turnaround time, which was originally 40 minutes.

“Fifteen minutes doesn’t seem like a long time, but in the context of having an hour to make a decision, that’s a big difference for us,” commented Newman, who worked with Genedrive on the test for about five years.

The kit is run using the Genedrive system, a benchtop device that can be used in an urgent care setting. The latest generation of the device includes a touchscreen and wireless connectivity, the company says, and clinicians can analyze patient samples for their MT-RNR1 m.1555A>G variant status before deciding on a treatment. antibiotic. Genedrive obtained CE-IVD marking for its MT-RNR1 test in 2019, and for the latest version of its system last September.

According to CEO David Budd, preclinical validation of the test by Genedrive demonstrated 100% sensitivity and specificity, but the results of the recent trial bolstered that data, with 99% sensitivity and 99% accuracy. In Budd’s words, these results “proved the effectiveness and capability of Genedrive’s technology at the point of care.”

The partnership with Manchester has also allowed Genedrive to improve its platform to make it easier to use and streamline workflow, based on user feedback. Budd said the inclusion of a touchscreen was designed for more flexible user interaction. Genedrive also added “fail-safe physical solutions” to prevent test failure by prematurely removing the test cartridge from the device, Budd said.

“The test [in the study] it was all done by nurses,” Newman pointed out, instead of experts in genetics or point-of-care diagnostics. has been adopted in clinical care.”

Manchester and Genedrive are now working to make the test more widely available across the UK. Newman said “there is a lot of enthusiasm” within the nation’s National Health Service for adopting the test. The Government’s Medicines and Health Products Regulatory Agency, he said, which oversees the regulation of IVDs in the UK, has advised that while such genetic testing is available to discern a potential negative reaction to a antibiotic, it should be adopted.

Newman also said that while there have been “pockets of real excellence” in terms of genetic testing within the NHS for years, the national health provider is working to expand access across the country, “so it doesn’t matter where you live, and it’s based on clinical need.” This means that it will be introduced throughout the country, which has around 67 million inhabitants.

The test is currently being rolled out in Manchester, with around 300 nurses being trained in the use of the Genedrive system at Saint Mary’s Hospital, Wythenshawe Hospital and North Manchester General Hospital, all of which are Manchester owned University NHS Foundation Trust. The intention, however, is to eventually make it available to everyone in the UK, Newman pointed out.

“We are in discussion with the NHS about how this test should be commissioned nationally,” Newman said. “It will take time in terms of training staff, making sure they are familiar with how the test works,” he said. “But we think it’s simple, and we’re excited for it to happen.”

The test was also endorsed late last month by the UK’s National Institute for Health and Care Excellence (NICE), which provides guidance on how to improve national healthcare. On March 29, NICE published a Medtech Innovation Briefing (MIB) on the MT-RNR1 test, which noted that the cost of the test was £80 ($105) per scan, and the Genedrive system cost £5,000, what the company confirmed. By comparison, NICE noted, the cost of pyrosequencing or Sanger sequencing to identify the same mutation would be £212 and £191, respectively. NICE pointed out that these tests are done after the fact, however, to retrospectively investigate the cause of hearing loss, unlike the Genedrive test, which is administered at the point of care to prevent hearing loss.

It is not clear if there are other commercial tests under development for the same indication. A Japanese research team published a method for detecting the mutation last year that relied on a chromatographic printed strip of single-stranded tag hybridization in the journal Genetic tests and molecular biomarkers. In the article, the authors suggested that the approach could be used as a companion diagnostic.

In its brief, NICE said uncertainties remain around Genedrive’s test in terms of studies, as well as the initial and possible future costs of using the technology. Still, Budd slammed the MIB positively, calling it a “significant step” in raising awareness of testing within the NHS, and said the brief will “ultimately help drive uptake” by providing NHS trusts considering new medical devices the information they need to make informed decisions. He added that the MIB, as well as the new JAMA Pediatrics study, also set out the next steps needed to include Genedrive’s test in clinical guidelines for routine use within the NHS.

In the meantime, Genedrive is already working with a UK distribution partner called Inspiration Healthcare to drive adoption in the country. Similar activities will be needed to raise awareness and increase market uptake across Europe to provide access to the product, Budd said. Ultimately, Genedrive also intends to expand market access in the United States, “where this test would be an attractive proposition and could be widely adopted,” he said, but did not. did not provide an estimate of when this might occur.

In European markets, the new Genedrive MT-RNR1 test is classified as a Class C device under the new European standard In vitro Diagnostics Regulations (IVDR), which will come into effect next month, with grace periods for devices approved before the effective date. In the case of Genedrive’s test, it will require authorization under the IVDR by 2026.

The UK has been moving to a new regulatory framework since leaving the EU in 2020. The MHRA said it would continue to recognize CE-IVD marks until July 2023, when manufacturers will need to obtain a UK Conformity Assessed, or UKCA, mark. , after examination by a designated body or “approved body”. Budd said Genedrive is on track to get a UKCA mark for its test by the 2023 deadline.

With this underway, the company and its partners are also considering other opportunities where rapid pharmacogenetic testing could be implemented into routine clinical care without major disruption to existing workflows. Budd said Genedrive is currently working on developing a stroke and cardiac marker test to screen for CYP2C19 mutations, for example.

“Like in newborn intensive care units, emergency admissions for strokes and heart attacks have tight timelines for clinical decision-making,” Budd said. He noted that drugs such as clopidogrel, sold as Plavix by Bristol Myers Squibb and Sanofi Pharmaceuticals, are often prescribed and can reduce further strokes or heart attacks in most patients. However, the drug will have no effect in 15-20% of patients, depending on their genetic profile.

“Rapid testing could provide clinicians with the information they need to prescribe the most effective drugs for each patient as quickly as possible,” Budd suggested.

Newman agreed that, in general, the availability of such a testing platform lends itself to further use in acute settings, such as stroke medicine. “It’s about those situations where you need a result very quickly, there’s no test available right now, and routine lab tests are taking too long to get you information. significantly,” Newman said. “These are the scenarios we are working on and thinking about.”

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