Roche's acquisition of privately held Boston-area molecular diagnostics developer Iquum, announced earlier this week, is expected to fill a hole in Roche's product portfolio, giving it a "full complement" of products for the molecular in vitro diagnostics market, a Roche executive said this week.
With the acquisition, which will see Roche pay Iquum shareholders $275 million upfront and up to $175 million in milestones, Roche gains Iquum's Liat (laboratory-in-a-tube) system, a 510(k)-cleared and CE-marked point-of-care molecular testing system, and an associated molecular assay for influenza A and B.
Roche believes these products will enable the company to quickly enter the POC MDx market, and it plans to work with Iquum over the next year to rapidly build out the platform's test menu, eyeing infectious diseases such as respiratory syncytial virus, methicillin-resistant Staphylococcus aureus, and Clostridium difficile, Paul Brown, president of Roche Molecular Diagnostics, told PCR Insider this week.
Since 2011, when the Liat Analyzer and Influenza A/B assay received US Food and Drug Administration 510(k) clearance, "the crude specifications and potential capabilities of the instrument and assays have now been realized and reduced to practice," Brown said. "Now the technology is really in a much greater stage of evolution and is ready for prime time. We've had our eyes on it for a considerable amount of time, and [Iquum has] done a lot of very good work over the last couple of years to bring it to the point where it's now ready for the outside world."
The Liat Analyzer automates all aspects of nucleic acid testing processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, and real-time detection, according to Iquum.
The system's workflow comprises collecting a raw biological sample such as whole blood into a Liat tube, capping the tube, scanning its barcode, and inserting it into the Liat Analyzer, which automatically executes all the required assay steps without further operator intervention and delivers a result in as little as 20 minutes.
The Liat Analyzer achieves this speed primarily through a proprietary PCR procedure called flow cycling. Traditionally, PCR machines have consisted of a large heating block that houses one or more reaction tubes and cycles its temperature to achieve the target denaturing, annealing, and extension temperatures — a process that requires between 30 minutes and several hours to complete.
The Liat, however, uses a flexible reaction vessel and a modular sample processor, which compresses various segments of the reaction vessel to heat and cool them much faster.
Other aspects of the Liat that make it suitable for POC use include the fact that it does not require an external computer, is equipped with network and other built-in connectivity ports, weighs just over 8 pounds, has a footprint of approximately 4 inches by 8 inches, and is capable of being battery or AC powered.
The system accommodates a variety of sample types, including whole blood, plasma, urine, and swab samples, and uses established nucleic acid test chemistries such as silica bead-based nucleic acid extraction and immunomagnetic sample enrichment. Both PCR and reverse transcriptase PCR assays can be run on the platform using either real-time or endpoint detection methods.
"Time to result … is critically important in point of care," Brown said. "You want a rapid turnaround time, and ideally you want lab-like performance. You don't want to have a point-of-care platform and assay that give you results not as good as you can generally get in a central lab."
Those two criteria, he added, "place a pretty high hurdle and barrier for dealing with point of care. And then if you think about the settings where you might want to see this used — in a hospital … an ER, an ICU … and of course if you can make the platform easy to use and ultimately get to CLIA waiver, then you open up the opportunity in physician offices and eventually in rapid clinics.
"What attracted us to Iquum were those very things: turnaround time; the fact that it produces laboratory-like results in a quick time; and it's easy to use," Brown added. "And from a synergistic perspective, it's PCR technology which is the bread and butter of [Roche's] business. It really is a hand-in-glove fit into our portfolio."
The Liat Analyzer currently has a "moderate complexity" designation under CLIA, but Brown said that Roche and Iquum intend to apply for a CLIA waiver, most likely sometime this year, which would allow the platform to be used in true near-patient settings such as physician clinics.
Brown said that Roche does not have specific plans to modify or redesign the Liat Analyzer any further, although he said the company needed to remain tight-lipped on the subject until the acquisition closes. However, he noted that Iquum had been working on increasing the throughput of the system, something Roche may also endeavor to do.
According to Iquum's website, one Liat Analyzer can perform between 10 and 20 tests per day, one test at a time. This throughput can currently be scaled by using multiple Liat Analyzers.
However, "Iquum [does have] a workstation which could take either four or eight tubes at a time," Brown said. "So they already have on the table the idea of having a workstation that would [enable] a larger throughput."
One area that Roche will tackle immediately is building out the test menu for the Liat Analyzer, which currently only runs the Flu A/B test. In 2011 Iquum executives told PCR Insider that the company was also working on assays for HIV viral load monitoring, influenza subtyping, and cytomegalovirus, and scientists from the company in 2010 published a paper in The Journal of Infectious Diseases demonstrating that an HIV viral load assay on the Liat Analyzer produced results comparable to that of commercial HIV viral load assays.
Since 2009 Marlboro, Mass.-based Iquum has also been awarded Small Business Innovation Research grants from the National Institutes of Health to support the development of HIV, dengue fever, human papillomavirus, and cytomegalovirus assays.
Brown also said this week that Iquum has over the past few years been developing assays for respiratory syncytial virus (to be combined with the Flu A/B test) and Streptococcus A. "Those are at a fairly advanced stage," he said. "We're also looking at MRSA and C. difficile. Going beyond that there is a whole list of potential assays we could put on there. And once the deal closes we'll be working with Iquum on [prioritizing] the list of assays."
Sales of Iquum's Liat Analyzer and Influenza A/B assay have been "relatively small," Brown said, although he noted that "a number of clinics" on the East coast of the US have used the platform and provided positive feedback to both Iquum and Roche.
"IQuum has no commercial organization today, which from their perspective of course is part of the attraction of coming together with Roche," Brown said. "We bring the technology along with our R&D and commercial power."
And from Roche's perspective, a true POC assay platform addresses a glaring hole in the company's molecular diagnostics product portfolio. The company has for years been a leader in thermal cyclers for laboratory-developed tests, offering its LightCycler platform in various configurations and throughputs. In addition, the company sells the Cobas 4800 platform, which combines the Cobas X 480 sample prep module and Cobas Z 480 real-time PCR analyzer into a single, fully automated molecular testing platform that can process up to 384 samples per day — ideal for centralized labs with lower throughput requirements.
Finally, the company is gearing up to launch the Cobas 6800, which will be able to process up to 300 molecular diagnostic tests in an eight-hour shift, and the Cobas 8800, which will be able to process up to 1,000 tests in an eight-hour shift. Roche unveiled beta versions of these systems at a conference about a year ago, noting that it would likely commercially launch the products in the second half of this year.
"This point-of-care piece was a hole in the portfolio," Brown said. "We've been looking for a couple of years for the right acquisition, and we're convinced this is the right one. Along with the fact that we're just about to launch our Cobas 6800 [and] 8800 platforms, which really operate at the other end of the spectrum … we now will provide a very comprehensive molecular diagnostics portfolio. It's very exciting times for us in molecular."