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At AMP Corporate Event, BioFire Dx, Cepheid Presentations Offer Early Look at MDx Pipelines

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NEW YORK (GenomeWeb) — A pair of companies tackling the molecular diagnostics market in different ways — BioMérieux's BioFire Diagnostics with comprehensive syndromic panels and Cepheid with highly targeted cartridge-based assays — last week sponsored presentations at the American Association for Molecular Pathology annual meeting in National Harbor, Md., in which clinical users shared preliminary data on highly anticipated products from the companies.

In addition, another BioFire customer discussed her lab's implementation of the company's FilmArray system and how it has changed the way the lab diagnoses gastrointestinal disease, while a Cepheid executive also updated attendees about the company's plans to expand beyond infectious disease into oncology.

BioFire FilmArray ME

During the BioFire corporate workshop, Loyola Medicine's Paul Schreckenberger discussed his lab's clinical evaluation of BioFire's FilmArray meningitis/encephalitis (ME) panel. BioFire began clinical evaluation of FilmArray ME in July with plans to seek US Food and Drug Administration clearance this year and CE marking after that.

With a run time of about an hour, the FilmArray ME Panel uses a combination of highly multiplexed PCR and melt curve analysis to simultaneously test for 16 different bacterial, viral, and fungal pathogens known to cause community-acquired meningitis and encephalitis.

Schreckenberger noted during his talk that the pathogens covered in the panel account for more than 90 percent of meningitis and encephalitis cases. His lab at Loyola is one of 11 sites across the US, including some pediatric centers, evaluating the panel.

Overall, the multi-center study had a total enrollment goal of 1,500 samples comprising residual cerebrospinal fluid leftover from the standard-of-care diagnostic of bacterial culture. Comparator methods for the study included culture for bacteria and PCR/sequencing for viruses and fungi.

Schreckenberger said that 83 specimens were excluded from the 1,500 for various reasons, and the final cohort contained about 60 percent adult samples and 40 percent pediatric samples.

Because the data he was presenting are supporting an FDA submission for FilmArray ME, Schreckenberger could not share exact sensitivity and specificity values, as the numbers are still being tabulated.

However, he noted that results of previous evaluations of the panel presented at conferences, such as IDWeek in Philadelphia last month, "give a good idea" of the panel's performance. Essentially, in one of those studies CSF samples from 39 HIV-infected patients with suspected meningitis in Uganda were analyzed with FilmArray, which detected Cryptococcus in all patients diagnosed with cryptococcal meningitis using standard techniques. In the other study, FilmArray ME detected pathogens in 15 of 48 CSF samples from patients admitted to Houston-area hospitals with community-acquired meningitis, while standard techniques identified pathogens in 14 of 48 samples.

Indeed, this ability of FilmArray ME to detect pathogens that may not be picked up using standard-of-care diagnostics is one of the test's most attractive features, Schreckenberger noted. He recounted that when his group began the latest clinical study it froze CSF samples and sent them to BioFire for testing. While most of the samples had been deemed negative using standard techniques, BioFire's testing with FilmArray ME revealed many organisms in the same samples, including enteroviruses in seven samples that had been specifically tested for that organism.

Schreckenberger said that his group is excited about the panel because it could potentially influence positive patient outcomes, allow clinicians to switch to targeted therapies sooner, reduce collateral damage from antibiotics, and shorten patient symptom duration.

"We think a lot of good outcomes will come from this syndromic panel … and we can't wait until we can implement it for real," Schreckenberger said.

BioFire FilmArray GI

Meanwhile, in another presentation during BioFire's corporate session, Patricia Cernoch, manager of the microbiology laboratory at Methodist Hospital in Houston, discussed her lab's implementation of the FilmArray Gastrointestinal (GI) panel, which was cleared by FDA in May and detects 22 bacteria, viruses, and parasites that are most commonly responsible for infectious diarrhea.

Cernoch said that before her "24/7, huge-volume" microbiology lab adopted FilmArray GI, it had to offer an array of stool-based tests for infectious diarrhea including culture and antigen-based assays.

Over the course of about five years, the lab calculated that it had, for example, a stool culture positivity rate of about 17 percent. Meantime, since implementing FilmArray GI, the lab has recorded a positivity rate of about 37 percent while drastically reducing the typical test turnaround time from about 48 hours to less than four hours.

Like Schreckenberger, Cernoch also noted that since implementing the FilmArray test, the lab's rate of specimens in which multiple organisms were detected "has increased dramatically … especially for viral pathogens like norovirus and pathogenic [Escherichia coli.]"

She also said that when it came time to convince doctors at the hospital to begin using the GI panel, laboratory technicians needed only to reference the FilmArray respiratory panel — BioFire's first FilmArray test which was implemented at the hospital last year — and "they were sold right there and then" because they had positive experiences using the respiratory panel.

"I've never seen a test take off like the respiratory pathogen panel did last year," Cernoch said, noting that the lab processed some 2,300 of the panels in one month last year.

The FilmArray panels are not without their drawbacks, however, as Cernoch noted that the cost to patients for the GI panel is high, although much cheaper in the long run when considering the cost of the usual bevy of tests a patient may have to endure. Labs will, however, see an increase in reagent costs, but "we are a firm believer that you have to spend some money to make some money, and we are saving costs elsewhere," she said.

Cepheid Xpert HIV

In a corporate workshop sponsored by Cepheid, Jeanne Jordan, a professor of epidemiology and biostatistics at George Washington University, discussed some early data from her lab's participation in a trial of Cepheid's Xpert HIV-1 Quant, still under development, but expected to launch with CE marking around the end of this year.

This assay, like all of Cepheid's Xpert single-use cartridge-based tests, uses automated microfluidics and nested PCR and runs on the GeneXpert platform. Unique features of the Xpert HIV-1 Quant include the fact that it targets a single gene; uses two internal quantitative controls, a low and a high control; and can be used on fresh and frozen plasma samples. The test's limit of detection is 40 viral copies/ml of plasma.

Jordan, who is also the director of the International Institute for Public Health Laboratory Management — a joint program between the Association of Public Health Laboratories and GWU — said during her talk that as part of the clinical evaluation, her lab compared the Xpert HIV-1 Quant to the FDA-cleared Abbott RealTime HIV-1 Assay for the m2000 platform. In 724 patient samples, the Xpert test had a concordance of 87.2 percent with the Abbott test.

Further comparing the two tests, Jordan noted that, overall, the Xpert test achieved slightly lower viral load quantification than the Abbott test at the low end of the detection range, but demonstrated a slightly higher overall detection rate than the Abbott assay.

Next, Jordan presented early data from her lab's evaluation of Cepheid's Xpert HIV-1 Qualitative assay as part of a larger multi-institution evaluation.

This test, which detects HIV-1 total nucleic acid in either whole blood or dried blood spots, is expected to launch with CE marking in the first or second quarter of 2015.

In a two-by-two comparison, the Xpert HIV-1 Qualitative was compared to Roche's Cobas AmpliPrep/Cobas TaqMan HIV-1 test v2.0 using 130 samples, many of which were taken from infants, Jordan said.

Overall, the Xpert test demonstrated approximately 99 percent concordance with the Roche assay. However, with its ability to deliver results in less than two hours, and the relatively compact size of the GeneXpert system compared to the dual sample prep/thermal cycler system required by the Roche assay, the Xpert test has the ability to be "truly near-patient … and allow immediate confirmatory testing of positive results," Jordan said.

Cepheid Oncology

Finally, during Cepheid's workshop, Michael Bates, ‎vice president of oncology R&D at the company, provided attendees with an update of Cepheid's oncology test pipeline.

To this point, the company has only developed and marketed Xpert tests for infectious diseases. However, the company has publicly noted since at least 2012 that it was developing tests for the GeneXpert system in the area of oncology.

At the AMP workshop, Bates said that the company has targeted four distinct product applications in oncology: early detection, monitoring, therapy guidance, and biomarker discovery. Current oncology tests in development at Cepheid include an Xpert BCR-ABL monitor, Xpert Bladder Cancer monitor, and Xpert Breast Cancer stratifier, Bates said.

Bates reported at the workshop that in very early clinical testing, the Xpert Bladder test demonstrated an overall sensitivity for symptomatic detection of 93 percent in a sample size of 171, compared to a sensitivity of 67 percent for Abbott's FISH-based UroVysion kit reported in the test's package insert. Meantime, for monitoring of bladder cancer, Xpert demonstrated an overall sensitivity of 86 percent in 270 samples, compared to the 73 percent reported for UroVysion.

The GeneXpert already had certain capabilities that made it conducive to these types of applications, but company engineers in recent years have been working to add to the system a high degree of multiplexing through its so-called "honeycomb" microwell configuration, as well as the ability to quantify biomarkers.

Bates noted that the GeneXpert microwell cartridge is currently being leveraged for a prototype breast cancer signature assay with potential follow-on products involving a prognostic or predictive RNA transcription signature.

Furthermore, Cepheid is eyeing rare mutation detection in circulating tumor DNA, with a prototype KRAS monitor for pancreatic cancer in the early stages of development; and methylated targets in FFPE, ctDNA, or urine with a prototype breast cancer monitor assay in early development and potential follow-on products such as assays for prostate, lung, and colorectal cancer.

In particular, in the area of breast cancer — where Cepheid has a collaboration in place with Oregon Health and Science University — Bates noted that the company envisions a reflex strategy for breast cancer management that could involve multiple Xpert assays: first, the breast cancer therapy stratifier that, depending on the result, would reflex to a triple-negative (ER, PR, and HER2) cartridge, a breast cancer recurrence signature test, or a HER2 resistance assay.

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