NEW YORK (360Dx) – Meridian Bioscience is currently developing an automated reader for colorimetric and fluorescence-based lateral flow immunoassays, which it anticipates submitting to the US Food and Drug Administration this year and possibly bringing to market next year.
The company expects submitting the instrument called Curian to the FDA along with an assay for three markers of Clostridium difficile infection. Meridian plans to ultimately provide an expanded menu of a dozen or so tests on the platform which will be oriented to testing in hospital labs as well as physician offices.
In a recent interview John Kenny, who was named Meridian's CEO about six months ago, provided background on the new project and a general update on the firm's Illumigene line of molecular tests and focus on malaria testing.
Kenny took the reigns at Meridian around the time that the company became the focus of an FDA investigation of blood-lead level testing kits manufactured by the firm's subsidiary, Magellan Diagnostics.
Meridian acquired Magellan in 2016 for $66 million, and problems with inaccurate lead test results came to light in early 2017, specifically involving tests performed on venous blood samples. The problems have since been linked to an incompatibility between reagents in the Magellan test and reagents in blood collection tubes supplied by Becton Dickinson.
However, Meridian noted in an investor conference last year that a majority of its lead test customers, which include many pediatric and obstetrics offices, use heel- or finger-stick blood samples and therefore were unaffected by the problem.
And, despite the setback, the overall upside of the Magellan acquisition was that it brought the firm a footprint in the physician office market, Kenny said.
"We have a significant physician office presence with our lead testing system, nearly 7,000 customers, and we have a lot of relationships there," he said, adding that the firm believes there is also an opportunity to do even more business with those customers.
Indeed, the Cincinnati-based firm has been a player in the point-of-care infectious disease diagnostics market for years, but Kenny said Meridian is ever mindful of offering better solutions to customers as time goes on.
Conversations with customers were part of the inspiration that led the company to consider a reader for its immunoassays. Meridian has been working on Curian for about a year, engaging a third-party instrument developer to design and build the platform.
Kenny said there are several advantages to using an automated reader as compared to reading a colorimetric test results by eye, including that it is less subject to variability and human error. Importantly for the physician office space, it will also likely require less expertise or training from the technologist running the test.
Since many customers are also "trying to do more with less," Kenny said the ability of the Curian instrument to connect with a laboratory information system, or LIS, can save time and person-hours by automatically transferring patient information and test results.
Although Meridian expects to port around a dozen of its existing ImmunoCard colorimetric assays to the reader, it will also be developing fluorescence-based tests.
This, Kenny said, will allow the firm to get even better performance out of certain tests, since fluorescent readout would tend to have a crisper signal.
While there are several companies that make both immunoassay products and molecular diagnostic products, Median expects diversifying its portfolio by adding the automated reader will enhance its offering to large hospitals and integrated delivery networks, or IDNs that would prefer to work exclusively with one vendor.
Looking for an edge in C. diff
The latter point is particularly true for C. diff, Kenny said, because "IDNs are always struggling with their protocols for trying to manage C. diff."
Testing sometimes involves immunoassays for C. diff toxins A and B or glutamate dehydrogenase (GDH), a metabolic enzyme produced by the bacteria. Molecular tests are more sensitive, and the Centers for Disease Control and Prevention has even anticipated that increased use of nucleic acid amplification testing would lead to the detection of more cases and an increased incidence of disease. NAAT tests are also more likely to detect carriers of the bacteria who are not necessarily ill or infectious.
New guidelines for C. diff testing from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America were published earlier this year suggesting that the choice of test should be based in part on how strict the lab or hospital is about deciding whom to test.
Essentially, if hospitals are only testing people with a high likelihood of having infectious C. diff — such as testing only unformed stool from patients with more than three episodes of diarrhea in 24 hours —then NAATs are the best choice. But, if they are testing samples less likely to be infectious, they may be better off with an algorithm involving screening out negative cases followed by tests to confirm positive results.
A recent meta-analysis also suggested that no single commercial assay is appropriate to be a stand-alone test for C. diff diagnosis, recommending a first pass with a highly sensitive test that has a high negative predictive value, such as a NAAT test or an immunoassay for GDH. Then, to rule out people who are not experiencing an active infection or who are carriers of the bacteria, the second test should have a high positive predictive value, such as an immunoassay for the A or B toxin of C. diff.
Historically, Meridian was one of the innovators of C. diff testing, and the company has offered ELISA-based tests in the past and now offers a C. diff immunoassay under its ImmunoCard brand as well as a NAAT test in its Illumigene platform.
However, "the reality is, over the last few years our products were getting beat up — it's a crowded market and we had some share loss in C. diff," Kenny said.
To build on Meridian's current foothold with an enhanced offering, the first test on the Curian menu will be a combined fluorescent assay for C. diff toxin A and B as well as GDH, Kenny said.
The firm is "working fast and feverishly" to submit Curian instrument and the test to the FDA later this summer, Kenny said, with a potential product launch in the early part of 2019.
For C. diff, however, Kenny said the only assay that can detect the toxin A&B and GDH targets simultaneously is the C. Diff Quik Chek Complete, a colorimetric test manufactured by TekLab and distributed by Abbott that does not run on the Alere Reader.
Meridian's fluorescent readout of its three-target test may also provide enhanced sensitivity, and using the automated reader, will allow for less user error and potentially quicker results reporting through the hospital LIS.
The test may also have some workflow advantages over the competition, Kenny said. "We have a lot of experience and skill in dealing with stool samples and optimizing them with lateral flow to get quality results," he said. The Meridian C. diff test in development will require two or three steps on the front end in order to run the sample on the Curian instrument, Kenny noted, while competing immunoassay tests from other manufacturers require at least twice as many steps.
Quidel manufactures toxin A and B NAAT-based tests in its AmpliVue, Solana, and Lyra molecular systems. Alere has also previously described work to develop a C. diff tests for its Alere i molecular platform.
But Meridian expects that the ability to provide both a sensitive fluorescent Toxin A/B and GDH test with the Curian reader, as well as a molecular test on the Illumigene system, will better support IDNs who would prefer to work with a single vendor for their C. diff solutions.
Subsequent tests on Curian will likely be ported from the firm's extensive line of colorimetric immunoassays. Kenny said that because the firm is targeting a new customer base for the Curian tests, it is unlikely that the new tests will cannibalize sales of legacy products.
Although an enterohemorrhagic Escherichia coli (EHEC) test will likely be the next assay on the Curian menu, Kenny said the new focus on the physician office market may also govern test choice and development.
"I'm actually looking at increasing some investment in R&D to try to go after ... things like flu and respiratory syncytial virus that are more physician office based," Kenny said, adding that the firm may do this "sooner rather than later." Meridian currently offers a CLIA-waived rapid flu A/B test from nasal and nasopharyngeal swabs on its ImmunoCard STAT! line.
Meridian uses a hybrid model of both direct and indirect sales. In the hospital space, Meridian works with Cardinal Health and Fisher Scientific, Kenny said, but it also has contracts with Henry Schein and McKesson, distributors who are trusted names in the physician office lab space. "We have pockets where we've built really strong relationships with our Schein reps, for example, and that's opened doors, but we have the opportunity to do more of that in the future," Kenny said.
Overall, providing an enhanced C. diff immunoassay with three targets in addition to its Illumigene molecular test may be attractive to IDNs seeking flexibility from a single vendor and help to win back some lost C. diff business. "We think it is going to be a fun opportunity to go play some offense," Kenny said.
In addition to the Curian C. diff test, Meridian has eight other rapid molecular assays on the point-of-need Illumigene system. These include tests for Group A Strep, pertussis, and mycoplasma pneumonia in the respiratory infectious disease space, and Group B Strep and herpes simplex virus 1 and 2 in a sexually transmitted disease domain. The company also has CE marking for two Illumigene malaria tests and an assay to detect chlamydia and gonorrhea.
According to a recent filing with the US Securities and Exchange Commission, the company has about 1,650 Illumigene placements, with 1,375 accounts having completed evaluations and regularly purchasing tests. Approximately 600 of these accounts are also regularly using two or more tests, which Kenny said tend to include C. diff, Group A Strep, and Group B Strep.
The firm is now developing an Illumigene cytomegalovirus test for use on saliva samples from newborns, since congenital CMV infection can lead to deafness. Neither universal screening nor targeted screening for CMV in newborns is yet recommended, but accumulating evidence suggests screening may be beneficial.
Meridian is also seeing uptake of its CE-marked malaria test in various settings, particularly in the Middle East, where people are returning from travel to malaria-endemic regions. The test is also being deployed at points of entry, with groups like the Italian Red Cross using it to test migrants from endemic areas, Kenny said.
The company is also working with ministries of health in regions where malaria is endemic as well as international programs like the Gates Foundation and Malaria No More. At this stage the firm is conducting proof-of-concept studies to see if the highly sensitive test, which can detect submicroscopic levels of the malaria parasite, could help in eradication efforts, particularly with pregnant women and newborns. It is admittedly challenging, Kenny said, since a molecular test provides increased sensitivity but is also costlier. "The reality is, if the less expensive tests aren't doing anything for you, at some point you've got to make the leap," he suggested.
So far, the firm has nearly 200 users of the malaria test, and Meridian is weighing the cost and opportunities of potentially bringing that test through the FDA as well.