The window for innovative diagnostics is open

The Covid-19 pandemic has presented a time-limited but immense window of opportunity for diagnostics companies. Changes in regulation and increased levels of investment are enabling radical innovations to have real impact, but only if they can be fast-tracked into new products which are cost effective and compelling to users. In this article we review some of the product releases and look at the long-term effects of this unique situation.

The WHO’s message of ‘Test, Test, Test’ echoed around the world and since the start of the Covid-19 outbreak, diagnostics companies have dropped their existing R&D programs to focus on SARS-CoV-2 test development.

The FDA’s Emergency Use Authorization (EUA) has enabled a quick route to market for products that have not received formal approval, and for many companies, the outbreak has stimulated significant cash injections from government and private organizations. The Covid-19 situation has meant products can be launched faster than ever before.

Engineers and scientists have been working intensively while the EUA window remains open, including teams at CDP who are in the final stages of developing a molecular platform for Covid-19 testing.

Most tests (~80%) authorized under EUA are molecular tests that detect the presence of viral RNA. Two companies (Becton Dickinson and Quidel) instead targeted detection of a protein within the virus particle (an “antigen” test) rather than detecting its RNA. The promise of home-based tests that detect antibodies (to determine if someone has had the virus) was unfortunately dashed by poor performance; the 26 authorized antibody tests are all lab-use and primarily involve large expensive equipment, rather than a low-cost pregnancy-style lateral flow strips that use a drop of finger prick blood.
 

Molecular tests on platform devices

First off-the-mark were companies that already have a device which can be repurposed for Covid-19 testing. Automated lab analyzer running PCR (the molecular ‘gold standard’ test) require little in the way of hardware modifications. The SARS-CoV-2 molecular assay is a relatively easy assay to develop for these systems as it is similar to other respiratory diseases (e.g. for Flu A/B). Roche, Thermo, Hologic and Abbott Molecular all released their tests on large scale hospital lab equipment during the same week in mid-March.

Companies producing near patient tests on existing platforms were quick to follow, and in the following week Cepheid’s Xpert Xpress, Mesa Biotech’s Accula and Abbott’s ID Now were all authorized. These systems are highly portable and CLIA waived, so they can be used outside of lab settings. The Abbott ID Now (the re-branded Alere-i) uses isothermal amplification (rather than thermal cycling) which enables results to be generated in as little as 15 minutes. Compare this with traditional PCR which takes ~40 minutes, and these should be ideal systems for mass deployment into schools, care homes, pop-up clinics, even for testing passengers while travelling on commercial flights.

However, whilst these systems seem an ideal method for de-centralized settings, sample collection can be error prone and the cost per test is relatively expensive compared with central-lab testing. Combined with lower throughput, it is currently more cost effective for people to self-isolate while their sample is processed in the central lab.
 

New CRISPR-based tests

Start-up companies are making use of this window of opportunity by building products around potentially disruptive technologies, which may have been too risky to develop in more normal times. An example technology is CRISPR, the game-changing technology for gene-editing – now heading rapidly into diagnostics. CRISPR uses the natural defense properties found in bacteria to protect itself, ironically, from viruses. It is now being used to rapidly detect specific nucleic acid sequences. Sherlock Biosciences recently received EUA for its CRISPR-based Covid-19 test kit – and is working to bring the technology into a point-of-care format which can deliver results in 20 minutes within a doctor’s office or even a supermarket. GlaxoSmithKline is also working with Mammoth Biosciences to bring CRISPR-based technology into a hand-held, fully disposable product format. These products are at an early stage, but future developments will advance detection capabilities and potentially enable faster and lower cost diagnostics compared with traditional approaches.
 

Fully disposable molecular tests

There is currently a race to launch fully disposable molecular devices that can offer lab-quality results from the convenience of the home. The vision again is that of a pregnancy-test type device, but one which carries out the complex assay functions of a molecular test. Many of the devices in development use isothermal amplification due to lower power demands and ability to cope with reduced sample preparation. These first-generation devices are going to be initially very expensive, but companies are pushing the boundaries and paving the way for more accessible testing.
 

Antibody tests – “the wild west” of testing

Very low cost, home-use lateral flow immunoassay tests involving just a single finger prick blood sample was hoped to be the ticket back to normality. These tests detect if a person has antibodies to the virus and therefore potential immunity to re-infection. Manufacturers were pushing these out under EUA despite very little in the way of supporting clinical data, but hopes were short-lived as high false negatives meant the tests were unsuitable. In some cases, results were so poor, it was comparable to flipping a coin. The only antibody tests released under EUA are lab-based tests, not home-based, and use conventional serum, plasma or whole blood sample collected by a phlebotomist.

Recent data suggests antibody tests are not actually very good at detecting if someone has had Coronavirus; many virus-positive patients have been antibody negative, so there appears to be other immune responses taking place involving T-cells, but that’s another topic.
 

Changing landscape

While existing lab analyzers are currently the workhorse of testing due to high performance, high throughput and low cost, relaxation of regulations and rapid cash injections have meant there are some highly innovative new developments which are pushing the boundaries and re-shaping the landscape of point-of-care molecular diagnostics.

Faster and lower cost point-of-care tests that are more convenient to the end user have the ability to provide results while-you-wait, meaning local outbreaks can be identified sooner and less time is wasted unnecessarily self-isolating. With greater access and clear social and economic benefits, more people will engage with testing on a regular basis. Covid-19 testing applies to the global population – it is not just a one-time event, but repeated frequently, time and again. The market size is huge, and the commercial opportunity is immense.

But the window of opportunity presented may be short-term due to the nature of the current global circumstances.  Companies will have to act fast in technology development to devise compelling embodiments that differentiate them from very similar competitors. Speed and innovative thinking will be key to win and maximize the opportunity.