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After Years of Groundwork, Rapid STI MDx Space is Inaugurated With Binx FDA Clearance

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NEW YORK – Rapid molecular testing for sexually transmitted infections has been on the horizon for two decades, and with US Food and Drug Administration clearance earlier this month of Binx Health's Binx io instrument and assay for chlamydia and gonorrhea, a new market opportunity may now have opened for many other tests and systems currently in development.

The clearance marks a milestone for one group in particular — Charlotte Gaydos and a point-of-care STI diagnostics development center she helped to establish at Johns Hopkins University.

Since 2007, Gaydos and her team at JHU has been attacking the problem of STIs on multiple fronts. That year, they won funding from National Institute of Biomedical Imaging and Bioengineering to support their own work on the subject and also to offer seed funding to startup companies developing new technologies.

Called the Center for Point-of-Care Technologies Research for Sexually Transmitted Diseases, the group has supported three early development projects for rapid molecular STI testing every year since and just finished the first year of its third five-year cycle, Gaydos said in an interview.

The center funded Binx in 2008, Gaydos said, back when it was known as Atlas Genetics and based in the UK. It gave a small grant to the then three-year-old spinout from the University of Bath and molecular diagnostics firm Osmetech, and the company in turn used the data generated to get more funding from the UK, Gaydos said.

Regarding Binx's clearance, Gaydos said, "We're very pleased. We sort of feel like they are one of our children."

Overall, it can take 10 years to bring a test to market, and the cost and effort of a clinical trial are a hurdle, Gaydos said, noting that the JHU center was one of the clinical trial test sites for the Binx io instrument and Chlamydia trachomatis and Neisseria gonorrhea (CT/NG) test.

There are numerous lab-based CT/NG tests currently commercially available, but the most similar test to Binx's might be the Cepheid GeneXpert CT/NG, Gaydos said.

However, the Binx test takes 30 minutes while the Cepheid test takes 90 minutes. Based on the turnaround time and instrument footprint, the GeneXpert would likely be considered by most end users to be more of a "near-patient" test rather than point-of-care. For true point-of-care designation, a test should produce results before a patient leaves the clinic, preferably within 30 minutes, Gaydos said.

Other rapid point-of-care molecular test systems cleared by the FDA and CLIA waived — including the Roche Liat, Abbott IDNow, and Mesa Biotech Accula — to date do not offer CT/NG testing but instead have stuck to a menu of respiratory pathogens. The BioFire FilmArray has a CLIA-waived version of its system for respiratory testing that can be run close to patients, and in 2015 participated in an evaluation of a research-use-only Film Array panel with nine STI targets.

Besides the rapid test time, the Binx system is quite small, so it can potentially travel deeper into decentralized testing spaces than a bulkier instrument.

The system can also multiplex up to 24 targets in a single test. In comparison, BioFire panels typically max out at 21 targets, and the next highest multiplexing for decentralized use might be the Meridian/GenePOC Revogene and Quidel Savanna instruments, both of which can run "mini-panels."

Now that a rapid instrument and STI test have finally crossed the long-awaited FDA-clearance threshold, Gaydos said that more are imminent. "They are coming along the pipeline," she said.

For example, the JHU center recently funded Novel Microdevices, a company working on a 20-minute CT/NG test. Gaydos also pointed out that SpeeDx is working on a CT/NG test that is not POC, but the company is working to shorten its test time, while Cepheid is also developing faster testing.

Indeed, Cepheid's line of Xpert Xpress tests has chemistries enabling 20-minute testing, and the firm has a few Xpress tests that have already been CLIA waived and has previously described plans to port some of its GeneXpert menu, which includes the CT/NG test, to the Xpress chemistries. SpeeDx is also developing STI tests on Cepheid's new "FleXible Cartridge" program.

Gaydos also noted a CT/NG and trichomonas test system from Click Diagnostics that is in clinical trials. It is a single-use, instrument-free test, she said, adding that she believes the company is also pursuing a CLIA waiver. There is also an instrument-free test from a company called Lucira Health, formerly known as Diassess.

Debkishore Mitra, co-founder and CTO of Lucira Health, said that the Binx io clearance is likely to have repercussions for the under-served STI market. "This is indeed an important and exciting development in the field of STI testing," he commented in an email. "The STI space has long been in search of a POC system ... [and] the work done by the Binx team also helps create a regulatory and, hopefully soon, a reimbursement pathway for other test developers," Mitra said.

For CT/NG in particular, the list of POC tests in development or available outside the US also includes the Bosch Vivalytic system, Hibergene's CE-marked CT/NG test that uses multiplexed isothermal amplification, MolBio's TrueLab system, a SlipChip-based test from Talis Biomedical, a test from startup Electronucleics that does not require amplification, a test that uses a smartphone reader from researchers at JHU, a five-minute CT/NG test from startup Prominex, and a multiplexed immunoassay-based test from Antelope Dx. And, firms like startup SAW Diagnostics are developing sample prep methods to speed up POC MDx for STIs.

The need for POC

Molecular diagnostics are often more sensitive and specific than immunoassays or culture-based testing. And rapid molecular STI testing in particular is "a great advantage because ... if you have patients come back in a couple of days [to get the test results] they've had time to transmit the infection to partners," Gaydos said. Further, test-and-treat protocols give an opportunity to council patients on how to remain free from STIs in the future and how to tell a partner so they can also get treated.

While STIs like chlamydia or gonorrhea are not usually life-threatening, they can have very dire consequences. They can significantly increase risk of HIV transmission, for example, and an untreated infection can also lead to pelvic inflammatory disease, which in turn can lead to chronic pelvic pain, infertility, adverse birth outcomes, and ectopic pregnancy, Gaydos said.

The US Preventative Services Task Force and Centers for Disease Control and Prevention guides that women under 25 be screened annually for chlamydia and gonorrhea in order to avoid these ill effects. The CDC also notes that there are approximately 3 million cases of chlamydia and 1 million cases of gonorrhea each year in the US, and that most infected women have no symptoms.

Gaydos said that research has demonstrated the more times a woman gets infected with chlamydia, the higher her risk is of infertility, with some estimates suggesting 1 in 12 women with untreated chlamydia will ultimately have difficulty conceiving. Rapid testing is therefore also a way to help women protect their fertility.

The CDC guidelines have also emphasized the benefits of using commercially available nucleic acid amplification tests for chlamydia and gonorrhea screening. Until the Binx clearance, most of the available testing was lab-based with turnaround times of at least 90 minutes.

The io system uses rapid PCR-based amplification and electrochemical detection, as previously reported. It was cleared along with a CT/NG test female vaginal swab samples collected by a clinician or self-collected by a patient in a clinical setting.

Gaydos also pointed out that Binx has a CE mark for the test, enabling its marketing in Europe, with claims for specimens from both men and women. 

Scientific validations

Rapid molecular STI testing has the potential to impact patient care.

In a randomized clinical trial published in the Annals of Emergency Medicine, Gaydos' group recently showed that, compared to a test that takes two to four days to come back, near-patient testing with Cepheid's test led to no patients being undertreated and a reduction in overtreatment by about half.

On the other hand, standard lab-based testing led to about 40 percent of patients not getting treated because they couldn't be contacted when the results were ready. Also, about half of the patients in the study were ultimately found by gold standard lab-based methods to be uninfected after they had already been prescribed antibiotics.

"It was a pretty good demonstration of what an immediate treatment can do –– it is accurate, you don't overtreat, and you don't undertreat," Gaydos said. These results could potentially be extrapolated to physician's office testing with a more rapid test, she suggested.

The Cepheid test takes 90 minutes, but Gaydos and her team have previously found that 30 minutes is the target time that patients would be willing to wait for STI test results. On the other hand, "For an ED, that's probably an OK test because people have to sit for six hours anyway," she said.

STI diagnostic testing is also often ordered in sexual health, women's health, and student health clinics. Cepheid has seen its tests adopted in STI clinics, for example. 

Gaydos and her team published a preliminary evaluation of the Binx io assay for the chlamydia target in the journal Sexually Transmitted Diseases last year, in which they also included results of a patient questionnaire to get at whether women liked point-of-care testing, and whether they were also interested in home testing in the future.

Specifically, the 284 women in the study were tested using self-obtained vaginal swabs with the Binx assay compared to the gold-standard Aptima Combo 2 lab-based test from Hologic.

The Binx test had a sensitivity and specificity of 84 percent and 99 percent, respectively, but adjudicating discrepant results by retesting them with the Cepheid Xpert CT/NG assay increased the sensitivity to 93 percent.

The researchers also found that 70 percent of women preferred to collect vaginal self-swab for POC testing if that option were available, 61 percent were willing to wait up to 20 minutes for results, and 26 percent were willing to wait up to 40 minutes for results if they could be treated before leaving the clinic.

Other recent studies have also evaluated the Binx test. For example, a prospective multi-site UK evaluation published in EBioMedicine last year found the chlamydia test on self-collected swab samples had a sensitivity of 96 percent and a specificity of 98 percent compared to lab-based testing with the CE-marked Becton Dickinson ProbeTec Qx CT/GC assay run on the BD Viper analyzer.

For the Binx test, Gaydos noted the STD study showed, "Not only is it a good test, but women like it."

But the study also provided data on how much women are willing to pay for testing. Specifically, it found that most women were willing to pay $20 or less for testing if they could mail a specimen collected at home, concluding, "[t]he low price point preferred by women in this study could be a barrier to adoption of POC tests by consumers, if and when POC tests become available over-the-counter."

Gaydos has spent many years surveying patients, and she highlighted that "the lay public does not know that they can get this" type of rapid STI testing. She said awareness campaigns might be beneficial, including advertising online and in newspapers and even directly to consumers in television ads and social media, as well as targeting professional organizations.

The testing will also likely be somewhat expensive initially, in part because of the cost of the disposable cartridge, Gaydos said, and this might make the testing less useful for resource-poor settings. For these settings, public health pricing or support from a non-profit like the Gates Foundation might help defray the cost.

Jeff Luber, CEO of Binx, said in an interview that Binx intends to place its instruments for free, and the cartridges can be manufactured "in the single digits at scale."  

The reimbursement rates for molecular CT/NG testing enable "a lot of margin" for the product, Luber also said, citing a Medicare and Medicaid reimbursement rate of $78. Experts the company has consulted tell it the CPT code already used for molecular CT/NG testing can be used for the POC testing.

For marketing, Binx is actually taking a different approach than might be expected.

"Our go-to-market strategy is not through direct-to-consumer advertising or building a large sales force," Luber said. "We're going after large partners who are having an increasing footprint in healthcare," he said, such as retail pharmacies and institutions that invest in women's health and sexual wellness. 

The firm also plans to license out the technology to companies with women's health sales forces, particularly ones marketing non-invasive prenatal testing and carrier screening who want to "put more products in the bags of those salespeople." Binx is looking for an exclusive partner for the io in OB/GYN and fertility clinics, Luber said. "We do think the power will come from a single, high-quality partner that's looking to have an exclusive advantage in the market," he said.

So, rather than building a sales team, the firm will keep a senior corporate development and medical liaison team, primarily focused on developing partnerships.

In terms of competition, Luber said that the market opportunity is in the realm of $10 billion, so, "There's plenty of opportunity for all." But, he said he thinks Binx will maintain its first-to-market leadership advantage because its cartridge has such high ability to multiplex.

The firm will soon validate a 30-minute molecular trichomonas test, he said, and is also developing a M. genitalium test, but whether these will be made into a small panel or individual tests will depend on the market demand.