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Cepheid Launches Xpert HPV in Europe, Pushing Further into Women's Health Market


Cepheid said this week that it has launched Xpert HPV, a one-hour molecular test for cervical cancer-related human papillomaviruses, in Europe after receiving CE IVD marking.

The assay, which runs on the company's GeneXpert system, closely follows the launch of the company's combined Xpert assay for chlamydia and gonorrhea, and should enable Cepheid to further compete in the women's health market with established players such as Roche, Hologic, Qiagen, and Abbott.

In addition, the assay is expected to be a boon for cervical cancer screening in developing countries, where Cepheid already has a significant installed base for its GeneXpert system due to the company's tuberculosis and TB drug resistance test.

Xpert HPV is a multiplexed real-time PCR test that targets the E6 and E7 oncogenes of 14 cancer-related HPV types. Early detection of the high-risk viral oncogenes E6 and E7 is critical, as they express E6/E7 oncoproteins in cervical cells and lead to cell cycle modifications that support conditions favorable to HPV viral replication. Studies have demonstrated that HPV viral genome integration into host DNA, and E6/E7 oncoprotein expression, correlate to the cervical cancer development.

Cepheid's assay specifically detects oncogenes from HPV 16 in one channel; HPV 18 and 45 in another channel; and HPV 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68 in additional channels on the GeneXpert system, Cepheid's flagship fully automated, cartridge-based molecular testing platform. Cepheid noted that if any of the high-risk HPV types in the additional channels are detected, the system only reports that qualitatively and doesn't provide the genotype.

Globally, HPV types 16 and 18 are associated with approximately 71 percent of all cases of cervical cancer, while HPV 45 is associated with approximately 6 percent of all cases, according to a cross-sectional worldwide study published in Lancet Oncology in 2010.

There is ongoing debate about the significance of the other HPV types in cervical cancer, but in general commercial assays are being developed that include a number of other types that at least have some association with the disease, according to the literature.

Cepheid or its collaborators have not yet published data regarding the performance of Xpert HPV. However, at November's Association for Molecular Pathology meeting in Phoenix, Philip Castle, chairperson and CEO of the Global Coalition Against Cervical Cancer and executive director of the Global Cancer Initiative, recapped a clinical cutoff determination and validation study as part of a Cepheid-sponsored presentation, which was webcast and recorded.

In this study, Cepheid and its collaborators at seven US sites collected two ThinPrep cytology specimens at the time of colposcopy from between 600 and 1,000 subjects. Castle noted that this was not a population-based screening study or a trial in support of US Food and Drug Administration marketing clearance, and as such the viral loads in patients would be expected to be higher than a screening situation.

One cytology specimen (specimen A) was compared with results from cytology, while the other specimen (B) was compared with Qiagen's Hybrid Capture 2 and Roche's Cobas HPV assays — the two most well-established FDA-approved molecular tests. All results were compared to pathology review by a panel of experts.

For specimen A, the Xpert HPV assay demonstrated 90.8 percent sensitivity and 42.4 percent specificity. According to castle, this compared favorably to cytology, which is the current gold standard and typically shows a sensitivity of between 50 and 70 percent.

For specimen B, Xpert HPV had a sensitivity of 90.9 percent and specificity of 43.5 percent. This also compared favorably to the competing molecular tests, with the Roche Cobas scoring 92.8 percent sensitivity and 39.3 percent specificity, and Qiagen's HC2 scoring 86.5 percent sensitivity and 47 percent specificity.

In general, Castle noted, there was "very good agreement" between the three molecular tests for HPV 16 and 18, the most high-risk HPV types.

Also, in a statement issued this week, Thomas Wright, professor emeritus of pathology and cell biology at Columbia University Medical Center, noted that in his group's initial clinical evaluations of a colposcopy referral population "we observed that, compared to conventional [nucleic acid amplification test] approaches, Xpert HPV delivered better-than-expected specificity with equivalent sensitivity — meaning equivalent numbers of true positives and significantly fewer false positives in women with negative biopsies."

Wright added that this observation "could be related to the fact that Xpert HPV is the first diagnostic test to use cell capture technology."

Wright could not be reached for further comment on this point, but in an email to PCR Insider a Cepheid spokesperson noted that "in essence, our test captures cells for analysis which gives us a specificity advantage without impacting sensitivity."

With the European launch of Xpert HPV, Cepheid enters into a highly competitive market for molecular HPV testing while bolstering its position in women's health testing — an area that the company only recently entered with the launch of Xpert CT/NG in Europe 2012, and FDA approval and launch of that same test last year.

Qiagen's HC2 assay had long been the market leader for molecular HPV testing before competing tests from Roche, and subsequently Hologic, hit the market. In the past few years, Roche and Hologic have been chipping away at Qiagen's market-leading position, both scoring important wins in recent months.

To wit, in March an FDA advisory panel unanimously recommended Roche's Cobas HPV test — which provides genotyping information for HPV 16 and 18 while simultaneously reporting on 12 other high-risk HPV types — as a first-line, primary screening tool. And last June, Hologic said that it was entering into an alliance with Quest Diagnostics to more broadly offer various tests, but HPV in particular, based on Hologic's Aptima family of products. Industry observers noted that this agreement came at the expense of Qiagen.

The Roche, Qiagen and Hologic HPV assays all have CE marking and have been cleared by the FDA. In addition, Abbott has marketed the RealTime High Risk HPV test on its m2000 instrument with CE IVD marking in Europe since 2008, but this test does not have FDA clearance.

In general, Cepheid believes it will compete with these diagnostic providers based on the speed and ease of use of its assay, as well as the relatively small footprint of the GeneXpert system compared to competitors' platforms.

"Frankly, it’s a far better clinical approach for the patient — accurate, specific, and a 60-minute window to results," the Cepheid spokesperson said.

In his AMP presentation, Castle lauded the assay's ease of use, noting that the workflow is "basically take a milliliter out of the ThinPrep specimen and put it in the machine."

In addition, Cepheid believes it has a leg up on competitors simply because it already has so many GeneXpert systems in the field running infectious disease and other molecular tests that the company has offered or years.

"With the largest installed base of any molecular system, the most obvious first approach [to gaining market share] is within that installed base as we continue to expand our menu of tests available to customers," the spokesperson said. "From there, we have higher-volume applications where our Infinity System leads the industry in overall capacity and throughput. We expect to do very well with this product overall." The Infinity system is essentially either 48 or 80 individual GeneXpert modules in a single automated platform.

According to a Cepheid presentation from the Raymond James investor conference last month, Cepheid currently has 5,509 GeneXpert systems in the field. In 2013, it placed a record 1,674 systems.

About 1,800 of these placements are through the company's high-burden developing country program, through which it places GeneXpert systems subsidized by various non-profit agencies into resource-poor areas of the world, primarily to run the company's Xpert MTB/RIF assay for tuberculosis and drug resistance.

However, Cepheid and its collaborators also see this as an opportunity for Xpert HPV. In particular, Castle noted that it may now be possible to deploy centralized or point-of-care HPV testing for cervical cancer screening in many of these areas.

"The excitement [around] this is [that] where there is TB, there are undoubtedly higher rates of cervical cancer," Castle said during his AMP presentation. "The fact that GeneXpert is placed in many of these high-burden, high-risk populations offers the opportunity to deliver cervical cancer prevention in these places … One can imagine almost a field kit at the smallest configuration [of the GeneXpert] … [as well as] high-throughput, centralized testing."

Cepheid had previously noted that it was aiming to commercialize Xpert HPV in the US in 2015. However, at last month's investor presentation, it noted that the new timeline for FDA clearance was in either 2017 or 2018. The spokesperson said that the company expects to update this timeline in May or June of this year.