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Regulation

As first OTC COVID-19 test raises stakes for consumer guidance, Abbott opts for prescription path

The rise of at-home COVID-19 testing highlights trade-offs between scalability and control  

Dec 17, 2020 | 2:13 AM GMT

FDA’s first authorization of an over-the-counter, at-home COVID-19 antigen test marks a major step in the intersection of individual self-monitoring and public health, and ups the ante on communicating uncertainty around results.  Abbott’s home test, authorized Wednesday, brings a narrower indication but higher volume.

Brisbane-based Ellume Ltd., which submitted an application for emergency use authorization (EUA) on Nov. 9, received authorization for its COVID-19 antigen test Tuesday.

The EUA allows the test to be sold without a prescription and used in any individual over the age of two, regardless of whether there is reason to suspect they might be infected.

On Wednesday, FDA expanded the reach of the point-of-care BinaxNOW antigen test from Abbott Laboratories (NYSE:ABT) by extending its EUA to include home use.  

Yet like the first FDA-authorized at-home COVID-19  test from Lucira Health Inc., home use of BinaxNOW requires a prescription, and is only indicated for individuals suspected of having COVID-19 by their healthcare provider. The indication is further limited to individuals within the first seven days of symptom onset.

BinaxNOW, which has the largest production capacity of any COVID-19 antigen test, has been heavily deployed by the Trump Administration in government-supported testing programs.  The company plans to deliver and administer 30 million at-home tests in 1Q21 and another 90 million in 2Q21; in contrast, Ellume is targeting delivery of  20 million tests to the U.S. market in 1H21. 

In opting for a prescription path, facilitated by digital health partner eMed, Abbott faces less uncertainty about how individuals will interpret and act on test results than it would in an over-the-counter setting.

Over-the-counter access to COVID-19 testing will be a key catalyst in the move toward broad asymptomatic screening to facilitate travel and in-person gatherings. But taking healthcare providers out of the equation makes it all the more important that manufacturers and regulators clearly communicate the possibility of false positives and negatives, a step FDA took when it announced Ellume’s EUA.

“For patients without symptoms, positive results should be treated as presumptively positive until confirmed by another test as soon as possible. This is especially true if there are fewer infections in a particular community,” the agency said.  “Individuals who test negative and experience COVID-like symptoms should follow up with their health care provider as negative results do not preclude an individual from SARS-CoV-2 infection.”

Ellume founder and CEO Sean Parsons told BioCentury that FDA required the company to prove subjects could understand the results they received, and take the correct next step afterwards.

Part of the reason Ellume’s test was more conducive to over-the-counter use than Abbott’s was the fact that it checks itself against internal controls and interprets results for the reader, similarly to a digital pregnancy test, while BinaxNOW consists of a stand-alone lateral flow “card” that requires human interpretation.

The trade-off is between interpretation control and scalability, as Ellume’s test is more expensive to manufacture than Abbott’s, a difference seen in their respective prices of $30 and $5. But for consumers, the price difference is evened out by the prescribing and interpretation services that accompany Abbott’s test, which bring its total cost to $25.

Couch-to-result

As part of their EUA announcements, both Abbott and Ellume provided details on the processes involved in using their tests, and the products’ at-home performance in specific patient subsets. 

For Abbott’s test, eMed determines an individual’s eligibility, facilitates test delivery to their home,  guides the self-collection process and interpretation of results through a live video visit with a trained provider, reports results to public health agencies, and creates a digital results “certificate” in Abbott’s NAVICA app, which the company says could be used to facilitate access to in-person venues.

When at-home results from 52 individuals were compared with an FDA-authorized, lab-based PCR test, BinaxNOW had a 91.7% sensitivity and 100% specificity in people seven days or less post-symptom onset. 

In a subset of those individuals whose PCR readouts had cycle threshold (CT) counts of 33 or below, the sensitivity jumped to 100%. CT counts reflect the number of thermal cycles a PCR machine undergoes before the target RNA is amplified enough to be detectable; the lower the CT count, the higher the starting concentration of viral RNA.

A separate study by University of California San Francisco researchers showed 93.3% sensitivity and 99.9% specificity in individuals with CT counts of 30 or lower, the company said.

Abbott cited emerging research showing SARS-CoV-2 can’t be replicated from samples with CT counts in the 30s, suggesting individuals with those levels of viral load wouldn’t be infectious, and said frequent antigen testing will be key to catching these individuals when they become capable of infecting others.

Ellume’s test comes with a smartphone app that provides user instructions, displays results and facilitates reporting to public health agencies, healthcare professionals, employers and educators. The test’s electronic analysis of its internal fluorescent readouts is communicated to the app via Bluetooth.

In a simulated home-use study with 198 participants, the test had an overall 95% positive percent agreement with an authorized PCR-based test, a measure of sensitivity, and an overall 97% negative percent agreement, reflecting its specificity.

For symptomatic COVID-19 patients, the sensitivity was 96% and specificity was 100%, while for asymptomatic individuals, the sensitivity was 91% and specificity was 96%. 

According to Ellume, the technology’s detection system overcomes “the sensitivity limitations of typical lateral flow technology.” Data on the test’s limit of detection (LoD), a measure of analytical sensitivity that enables comparison to other tests, was not available in time for publication.

The Australian company, which has its second headquarters in California, has a home flu test partnered with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) under review by FDA.

Ellume received a $30 million grant from NIH’s Rapid Acceleration of Diagnostics (RADx) initiative to scale up manufacturing. Through Ellume’s participation in RADx, the test was independently validated by researchers in the RADx Testing Core from Emory University, Georgia Institute of Technology and Children's Healthcare of Atlanta Inc.

As antigen tests, both Ellume and Abbott’s products detect SARS-CoV-2 protein fragments via immunoassays. Lucira Health’s at-home product is a loop-mediated isothermal amplification (LAMP) test, which detects viral RNA but is distinguished from PCR by its lack of temperature cycling.

More at-anywhere

Wednesday saw two other announcements that could advance at-home COVID-19 testing.

Sherlock Biosciences Inc. received a $5 million grant from the Bill & Melinda Gates Foundation to accelerate development of its instrument-free INSPECTR (Internal Splint-Pairing Expression Cassette Translation Reaction) diagnostics platform, which uses synthetic biology to enable SARS-CoV-2 detection in at-home or resource-limited settings.

In May, the company received a $7.5 million grant from The Open Philanthropy to support both INSPECTR and SHERLOCK, the CRISPR-based platform behind the company’s FDA-authorized lab test.

Separately, HHS announced the sixteen top entries for its “COVID-19 Diagnostics At-Anywhere Design-a-thon,” which aims to increase the speed, quality, comprehensiveness and utility of COVID-19 testing data.

These projects, including the overall winner from Oracle Corp. (NASDAQ:ORCL), were focused on ways to report and disseminate COVID-19 results.

The agency directly connected the need for optimized information flow to the growing prevalence of at-home tests. 

“These capabilities will be necessary for data capture and reporting when at-home, non-prescription and over-the-counter tests are authorized and begin saturating the market,” the HHS statement said. 

BioCentury & Getty Images

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