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On Heels of FDA Approval, Cepheid's Xpert CT/NG Test Performs Well in Multi-Center Clinical Study


Cepheid's Xpert CT/NG assay for detecting Chlamydia trahcomatis and Neisseria gonorrhoeae is at least as accurate as two other commercially available molecular tests for the bacteria, according to the recently published results of the beta phase of a multi-center clinical study involving more than 3,000 female and male patients.

According to the study's authors, these preliminary results – combined with Xpert CT/NG's ease of use and fast turnaround time – make the test promising as a tool to diagnose patients at the time of examination and improve chlamydia and gonorrhea control efforts.

In addition, the results are just the tip of the iceberg as results from a larger clinical study involving more than 7,000 patients are likely to be published later this year, and are expected to drive adoption of Cepheid's assay in both centralized hospital-based clinical laboratories and smaller labs at physicians' clinics, Cepheid CSO David Persing said this week.

"What we got in terms of performance … was quite excellent from the initial phase of the evaluation, and comparable to if not better than competing technologies," Persing told PCR Insider this week. "The clinical trial evaluation is much larger, and I think if anything the data are even more convincing about performance. The full clinical trial will be presented later in the year."

Cepheid obtained CE marking for Xpert CT/NG last year and US Food and Drug Administration approval for the test in January with a moderate complexity rating under the clinical laboratory improvement amendments.

Xpert CT/NG is a nested PCR-based test that runs on the company's fully automated, sample-to-answer GeneXpert system. The assay detects DNA from C. trachomatis and N. gonorrhoeae from female endocervical, vaginal, and urine specimens; and male urine specimens from symptomatic and asymptomatic patients in less than two hours.

More specifically, the assay targets two highly conserved, non-contiguous chromosomal targets unique to N. gonorrhoeae and a single chromosomal target from C. trachomatis.

In a study funded by Cepheid and published last week in the Journal of Clinical Microbiology, clinical researchers led by the laboratory of Charlotte Gaydos at Johns Hopkins University School of Medicine compared the clinical performance of Xpert CT/NG with a benchmark "patient infected status" from 1,722 female and 1,387 male volunteers at a number of different clinical sites.

The group determined this patient infected status based on the results of two other commercially available "first-generation" molecular tests: Gen-Probe's Aptima Combo 2 running on the Tigris system, both of which are now sold by Hologic after that company acquired Gen-Probe last year; and Becton Dickinson's ProbeTec assay running on the BD Viper system.

The study's authors collected three endocervical swabs, one patient-collected vaginal swab, and a urine specimen from each woman; and a urine specimen and two urethral swabs from each man. The researchers collected the urethral swabs from males solely for the purpose of determining the patient infected status using the Gen-Probe and BD tests, as Cepheid sought FDA clearance only for male urine samples for its assay.

Based on the patient infected status, a total of 82 of 1,722, or 4.8 percent, of female subjects were infected with C. trachomatis, and a total of 23 of 1,722 women, or 1.3 percent, were infected with N. gonorrhoeae. Meantime, 81 of 1,387 men, or 5.8 percent, were infected with C. trachomatis, while 50, or 3.6 percent of males, were infected with N. gonorrhoeae. Forty-seven subjects were infected with both, and symptoms were reported in 27 percent of study participants.

Relative to the patient infected status, Xpert CT/NG demonstrated a sensitivity and specificity for C. trachomatis for patient-collected vaginal swabs of 98.7 percent and 99.4 percent, respectively. Meantime, the assay demonstrated sensitivity and specificity of 97.4 percent and 99.6 percent, respectively, from endocervical swabs; and sensitivity and specificity of 97.6 percent and 99.8 percent, respectively, for female urine specimens.

Using male urine specimens, compared to the patient infected status, Xpert CT/NG demonstrated a sensitivity and specificity of 97.5 percent and 99.9 percent, respectively, for C. trachomatis.

For gonorrheal infections, sensitivity and specificity using vaginal swabs were 100 percent and 99.9 percent, respectively; while sensitivity and specificity from endocervical swabs were both 100 percent. Meantime, female urine specimens yielded sensitivity and specificity of 95.6 percent and 99.9 percent, respectively; while male urine specimens resulted in sensitivity and specificity of 98 percent and 99.9 percent, respectively.

The study's authors noted that there were no statistical differences in performance estimates among all three assays used; and that the Xpert CT/NG's performance characteristics were equivalent to the two comparator assays.

They also wrote that the assay performed well for both asymptomatic and symptomatic patients, making it useful for both diagnosis and screening; and that the test's high accuracy combined with other attributes of the GeneXpert testing system make it promising for such applications.

"A particularly distinctive attribute of the Xpert platform is its easy-to-use, cartridge-based format and automated sample preparation and extraction process," the researchers wrote. "This makes the assay easy and well-suited for use at sites where clinical care is provided, providing the potential to reduce the time needed to obtain test results to guide therapeutic decision making."

Further noting that the assay's hands-on time is about five minutes, and that the platform provides results in under two hours, the researchers wrote that the ability of Xpert CT/NG to provide test results and treat patients "before they leave the clinic or doctor's office has substantial potential to … reduce complications, and may be cost-effective depending on the cost of the assay, the time patients are willing to wait, and the number of patients who do not return to a clinic for their result."

Competitive Landscape

Besides the two first-generation assays to which it was compared in the JCM study, Xpert CT/NG enters a rapidly crowding and increasingly competitive landscape for rapid molecular testing of the bacteria.

For instance, Roche and Abbott both offer FDA-approved tests for their fully automated clinical testing systems; and other diagnostic developers such as Alere and Qiagen are working on CT/NG assays for their testing systems.

In December, Meridian Bioscience said that it completed beta trials for two new isothermal Illumigene assays for Chlamydia trachomatis and Neisseria gonorrhoeae in both swab and urine samples, and said that it expected to begin clinical trials to support a US regulatory submission for the products this year (PCR Insider, 12/13/2012).

Companies like Network Biosystems and Atlas Genetics are also pursuing rapid molecular tests for chlamydia and gonorrhea, but are farther from commercialization.

Cepheid's Persing said this week that the company is confident that several features of Xpert CT/NG will help it snag a significant portion of market share, echoing comments made by CEO John Bishop during a conference call earlier this year (PCR Insider, 1/31/13).

"The design of the test … [is] absolutely unique and the targets are unique – they were discovered during an in silico process, initially, and then validated in the laboratory," Persing said. "This was meant to overcome some of the shortcomings of a lot of the targets that have been used in first-generation tests."

Further, two independent targets in the NG portion of Cepheid's assay "both have to be positive for the sample to be declared positive … which adds a layer of specificity that we believe will be an important aspect of test performance going forward," Persing said. "That was shown in this study and will be shown on an even larger scale in the clinical trial."

In addition, the Xpert CT/NG is the first molecular test for the bacteria to receive a moderate complexity CLIA rating, which "will allow the technology to be much more broadly disseminated," Persing said. "A moderate complexity lab in a physician's office complex … could run this test, now, for the first time."

And lastly, Cepheid believes it has an advantage in terms of turnaround time – not necessarily because of the actual time it takes to perform the test, but because the cartridge-based design allows on-demand testing.

"When we talk to physicians, especially emergency room docs, they want fast turnaround time," Persing said. "They see a lot of these symptomatic patients in the ER setting, and they want to rule out STIs. This type of cartridge-based technology enables much faster turnaround time than first-generation methods, which are all batch-based, so that's a real advantage, as well."

As part of his comments in January, Cepheid's Bishop noted that the company saw its first revenue from Xpert CT/NG outside the US in 2012 from existing Xpert accounts in northern Europe and new accounts in southern Europe.

He also said at the time that the majority of early adopters were bringing a CT/NG molecular test in house for the first time, but that Cepheid has seen "a promising contribution" from customers converting from first-generation tests from BD, Roche, Abbott, and Hologic's Gen-Probe.