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Qiagen, NeuMoDx Aim to Quickly Build Out Test Menu for High-Volume MDx Systems

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NEW YORK (GenomeWeb) – Qiagen is taking aim at the high-throughput, high-volume molecular diagnostics market through its recently announced partnership and merger agreement with molecular diagnostics developer NeuMoDx.

The deal calls for Qiagen to initially distribute the NeuMoDx N288 and NeuMoDx N96 fully integrated molecular testing platforms in Europe and other ex-US markets, while Ann Arbor, Michigan-based NeuMoDx will continue to market its systems and tests in its home country.

Further, Qiagen, which currently owns about 20 percent of NeuMoDx, has the right to acquire all remaining shares for the predetermined price of $234 million, subject to regulatory and operational milestones.

The move gives Qiagen yet another piece in what is arguably the most comprehensive clinical molecular testing portfolio in its peer group, a portfolio that already includes its flagship QiaSymphony RGQ modular platform for highly automated real-time PCR testing; the Digene HC2 High-Risk HPV DNA test; the GeneReader NGS system; and, as of earlier this year, the QiaStat-Dx platform for syndromic infectious disease testing.

The deal will also make Qiagen more directly competitive with heavy hitters in the high-volume molecular testing market such as Abbott, Hologic, and Roche — provided Qiagen and NeuMoDx can rapidly build out a test menu, a contingency on which the completion of the merger agreement hinges.

"We have to quickly develop a competitive menu," said Thierry Bernard, senior vice president for molecular diagnostics at Qiagen. "In that market of high-volume, low-plex [testing], you basically have to have a group of 10 assays to compete. Once you have that … you can be very competitive and make the difference with the features of the platform."

Those 10 tests, according to Qiagen, are for hepatitis B and hepatitis C viruses; HIV; cytomegalovirus, Epstein-Barr virus; group A Streptococcus; influenza A/B and respiratory syncytial virus; Trichomonas vaginalis; and factor II and factor IV (Leiden) genotyping.

Neither Qiagen nor NeuMoDx currently offer any of these tests on the system, but the companies said that they have been working together for some time and most of the required assays are in development. Both systems are already CE-IVD marked, as are tests for group B Streptococcus (GBS) and Chlamydia trachomatis/Neisseria gonorrhoeae, as well as laboratory-developed test functionality. Qiagen is commercially launching all of these items this week at the European Society of Clinical Virology congress in Athens.

In the US, where NeuMoDx will continue to market its platform and tests independently, the N288 system and a GBS assay received US Food and Drug Administration 510(k) clearance in July, and a CT/NG test is currently under FDA review.

"As you see we have an ambitious CE marking program, but at the same time [NeuMoDx is] working with the FDA … and we want to make sure we keep on track so that menu available in Europe will also be FDA [approved] by the time of the merger — that's the main objective," Bernard said. "We need to keep the development of the assays on track, and … those 10 assays are very well staged in 2019, and we want to push them through the FDA equally rapidly."

Provided the companies can achieve these goals, they believe the NeuMoDx platforms offer several features that distinguish it from other competing products, such as the Abbott m2000, Hologic Panther Fusion, and Roche Cobas 6800/8800, all of which have FDA clearance and CE marking and have a significant head start in terms of market penetration.

As previously reported, both the N288 and N96 are based on the same core liquid handling, microfluidics, and real-time PCR technology, and both offer true random-access sample loading with the N200 capable of running up to 30 different assays and the N96 capable of running up to 20.

The N288 has the higher throughput of the two platforms and can process up to 340 samples per eight-hour shift with a test turnaround time of 40 to 80 minutes. The N96, which is more ideal for medium-throughput needs, can process up to 150 samples in an eight-hour shift with a similar test turnaround time. The N288 has a footprint of about 180 cm by 109 cm (6 feet by 3.5 feet — anywhere from two to four times smaller than competing instruments), while the N96 footprint is about 136 cm by 108 cm (about 4.5 feet by 3.5 feet).

The relatively rapid test turnaround time (most competing platforms take three hours or more to produce results) is enabled by patented extraction technologies, microfluidics, and silicon-based thermal cycling. Both systems and all tests will use the same consumables, with no reagent preparation required and onboard reagents stored at room temperature for up to two months.

"Everyone claims that their systems are unique, but I think even the competition would admit that this is a very different approach to an integrated molecular diagnostics system," said NeuMoDx Chairman and CEO Jeff Williams. "To achieve all of these features and customer benefits … it required a different approach. You couldn't follow the Roche or Hologic approach where you simply use a liquid handling workstation and microtiter plates and move liquids from point A to point B to point C. You wind up with a bigger and bigger system … which comes in three or four pieces … to do a moderate level of throughput."

An alternative approach, he noted, is one taken by companies like Cepheid with its Xpert systems and Becton Dickinson with the BD Max, where the system is more unitized and typically cartridge-based, with each cartridge capable of running one patient sample with one set of PCR reactions. "Both those approaches have limitations, and they both have good aspects," Williams said.

NeuMoDx's systems, he noted, "kind of take the best of both worlds [and] avoid the downsides of both." They feature liquid-handling gantries, but "only for moving large specimens around," for instance, taking a specimen out of a collection tube and putting it onto an extraction plate where lysis and nucleic acid-bead binding occurs. This is then moved internally into a microfluidic cartridge, "and from that point on everything happens in a microfluidic world," Williams said.

"By doing this we're able to gain all the advantages of a clinical chemistry analyzer for molecular," he said. "Put the specimens on the system and let it go and that's all you need to do. The system will tell you if you need more consumables, but otherwise it's just load the specimen tubes and walk away."

User perspective

One early user of the system is TriCore Reference Laboratories, where Stephen Young, director of research and clinical trials, oversees a lab that conducted the clinical trials on NeuMoDx's GBS assay to support FDA clearance.

Young knows several of the NeuMoDx platform developers from their days at HandyLab, where they developed a platform that eventually became the BD Max. In fact, the group used the BD Max as a predicate device for the NeuMoDx clinical trial, and the NeuMoDx system "performed well if not better" than the BD system as well as culture, Young said. The lab is currently preparing its study results for peer-reviewed publication.

Young said that he doesn't run the NeuMoDx instrument himself, but that all of his lab technicians that have used it have reported it to be "very simple" to use.

"There's no refrigeration — it's all freeze dried in little trays, so the amount of consumables you have to have on site is small," said Young, who is also a professor of pathology at the University of New Mexico. "From that perspective it's a very nice instrument."

Young also lauded the platform's ability to run both IVD assays and LDTs and said that NeuMoDx was smart to have developed a smaller version (N96) of its original platform (N288).

"People began to ask them, 'What about labs that don't need a big instrument?'" Young said. "They just took their instrument and made it smaller. All the same chemistry, everything. Even a big lab like mine needs redundancy. But two of those things are pretty big. If you have two, but one's a little smaller, you can run some groups of assays on the smaller one and run other [assays] where you have big volume or need throughput on the bigger one."

Young said his lab at TriCore currently runs multiple "big boxes," including the Hologic Panther for CT/NG and the Roche Cobas 6800 for its viral load assays. He added that TriCore is not currently using the NeuMoDx platform clinically, but there's a good chance in the future should the company quickly build out the test menu.

"The menu has to be built out, but everyone suffers from this when they bring out a new instrument," he said. "Now that they have the backing from Qiagen, and deeper pockets, I think they can get a lot of assays on this platform very quickly — as quickly as they can get through today's regulatory process."

Cannibalizing sales?

Qiagen already offers its customers laboratory automation for molecular testing with its QiaSymphony platform, which, when coupled with its Rotor-Gene Q thermal cycler, can theoretically run many of the same tests as the NeuMoDx platform. Qiagen's Bernard said that the NeuMoDx platforms may cannibalize sales of this combined platform, but only to a certain extent.

"Because of the evolution of technology … we now have two kinds of markets in molecular infectious disease testing," Bernard said. "You have a market from 15 or 20 years ago — let's call it the non-integrated market, where you still use different components such as the QiaSymphony and the RGQ, and many labs are still using that. But the market has clearly evolved to more integrated PCR technologies."

And while it's true that QiaSymphony is an assay system when coupled with a thermal cycler like the RGQ, "it is also a unique front-end system because of its very high-quality extraction and purification of nucleic acids," he added. "While we see the non-integrated market falling in favor of the integrated PCR market, we see QiaSymphony still as a standalone extraction system that is ideal for very esoteric testing or, for example, [cell-free DNA] extraction."

Qiagen may also develop a human papillomavirus assay for the NeuMoDx system, which would compete with its own Digene Hybrid Capture 2 (HC2) high-risk HPV test. Qiagen was one of the earliest entries into the molecular HPV genotyping market with that assay, which is not PCR-based and uses chemiluminescent detection. It was and still is a valuable franchise for the company, but it has been losing market share to competitors for a few years now, something the company has spelled out explicitly in its quarterly earnings reports.

"This is a discussion we are currently having with [NeuMoDx]," Bernard said, adding that the company has access to an HPV test from a previous partnership that it can port to the NeuMoDx system. "Indeed … we will probably add HPV very quick and early during 2019," he said.

"We have been losing ground on HPV, while still being present in all the major labs, and we didn't lose ground that much on genotyping but on automation," Bernard added. "This will help consolidate our position. HPV testing has gone down in price very severely, but at least this helps us give an answer when people say, 'I'd really like to [do HPV molecular testing], but if you could complement it with automation I would be interested."