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SpeeDx Pursues Clinical Trials Ahead of Anticipated FDA Clearance for M. Genitalium Assay

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NEW YORK (GenomeWeb) – SpeeDx has begun US clinical trials for its Mycoplasma genitalium assay called ResistancePlus MG in anticipation of Food and Drug Administration 510(k) approval for the assay next year.

CE marked in 2016, the assay both detects M. genitalium and identifies biomarkers in the bacterium's 23S rRNA that confer resistance to the macrolide antibiotic azithromycin.

Clinicians typically detect drug resistance in sexually transmitted infections by performing cell cultures in the presence of antibiotics. However, M. genitalium cell culture is only performed in two laboratories worldwide due to technical demands and slow sample-to-answer results.

SpeeDx developed the ResistancePlus MG assay to quickly diagnose patients with the STI so treatment can begin as soon as possible and the chances of antibiotic resistance is minimized. Currently available in Europe and commercially available in Australia, the assay uses vaginal swabs in women and urine sample from men to detect drug-resistant biomarkers of M. genitalium in patients.

In a study published earlier this month in Clinical Infectious Diseases, researchers at the Melbourne Sexual Health Center established a three-tier resistance-guided therapy approach for patients with varying levels of M. genitalium infection.

"We wanted to be able to treat patients properly and reduce the number of repeat visits and prescriptions, and [avoid] the often disappointing news that treatment had failed," sexual health physician and project director Timothy Read said in an email.

First, clinicians replaced azithromycin with doxycycline as the frontline treatment for nongonococcal urethritis, proctitis, and cervicitis. The team then used the ResistancePlus MG assay in 244 patients with infections to detect M. genitalium and the presence of macrolide resistance mutations, and detected macrolide-resistant M. genitalium mutations in 167 patients.

Afterward, clinicians treated patients based on whether they had macrolide-susceptible infections or macrolide-resistant infections. Overall, the researchers reported an overall cure rate of greater than 92 percent for M. genitalium infections.

While Read noted that the M. genitalium assay delivered results within a couple of days, he emphasized that by combining this type of test with a rapid PCR platform, the assay "could enable same-day resistance-guided therapy." Although his team did not focus on clinical utility, Read said that the assay's sensitivity and specificity has ranged from 95 to 100 percent in previous studies.

"[F]ailure to detect a mutation is highly likely to lead to treatment failure if a macrolide is used," he explained, "so we assume few if any of the successful macrolide treatments —[almost] 95 percent of cases — included false negatives."  

In terms of limitations, Read noted that his team only had Sanger sequencing results available for the four cases where azithromycin treatment appeared to fail. In one case, the assay misclassified the pre-treatment sample as macrolide-sensitive rather than resistant. Read's team will therefore analyze further sequencing results in a latter publication.

In an additional study presented at the European Congress of Clinical Microbiology and Infectious Diseases in April, healthcare scientist Jayne Harwood and her team at Freeman Hospital in the UK examined the prevalence of M. genitalium in symptomatic patients in northeastern England. In an email, Harwood explained that once the team determined the prevalence of the pathogen, they aimed to find the rate of resistance to macrolide treatment.

Harwood and her team tested 322 patients presenting symptoms or contacts of M. genitalium with 214 male and 81 female individuals. They found that the SpeeDx assay produced an 18 percent positive detection rate in the population. Because of the high rate of resistance, the researchers believe that the assay should be applied to symptomatic patients.

In anticipation of potential de novo clearance of the assay for the US market, SpeeDx commenced clinical trials using the assay in May. As part of the ongoing multicenter lab collaboration, the firm will work with up to 10 collection centers across the US and focus on male and female populations at multiple risk levels for contracting M. genitalium.

SpeeDx has partnered with labs at Johns Hopkins University, TriCore Reference Laboratories, and the University of Alabama, Birmingham to perform the ResistancePlus MG assay on collected patient samples. SpeeDx CEO Colin Denver said he’d like to  to reach the whole spectrum of socioeconomic and ethnic groups with its collection sites, which currently service many low-resource settings in high STD prevalence areas in the US.

In addition, Denver mentioned that the firm has a number of clinical utility studies planned and underway that will generate payor awareness. He explained that the studies will address economic benefits of improving cure rates with resistance-guided therapy.

According to Denver, the clinical trial will enroll up to 3,000 patients, capturing M. genitalium prevalence "across a wide snapshot of demographics and risk factors." He believes it will also deliver information on the levels of antibiotic resistance in the different populations and "could inform future guidelines for treatment."

He anticipates SpeeDx will have all data ready for an FDA submission by the end of December, and clearance could come by late April 2019.

If the agency approves SpeeDx's ResistancePlus MG assay, the firm will be entering a crowded STI detection market. Hologic, for example, has developed an assay for M. genitalium that runs on the firm's Panther Fusion PCR-based platform. In addition, Roche recently received CE marking for the Cobas TV/MG test on its automated Cobas 6800/8800 platform, which detects pathogens such as M. genitalium in symptomatic as well as asymptomatic patients.

UK-based startup Atlas Genetics is also developing STI detection tests that will include species including M. genitalium. The firm recently received a two-year Phase II contract from Innovate UK worth £2 million ($2.6 million) in August 2017 to expand the menu for its rapid diagnostic platform called Io.  

Denver believes SpeeDx's technology distinguishes itself from competitors due to its ability to detect resistance biomarkers simultaneously with the bacterial species.

"In our experience [during] the last two years, that piece of information is critical to the clinician treating the patient," Denver explained. Being able to inform about antibiotic resistance "gives the treating doctor confidence that they're prescribing the correct drug for the infected patient."

If it receives FDA approval, SpeeDx envisions marketing the assay to hospital-based labs and reference labs. The assay is currently a laboratory-developed test, meaning it requires a lab to run the test, but Denver said that the firm aims to "weave the assay into a near-patient format, but it is still under development."

Denver declined to comment on the eventual cost of the assay. He noted that the reimbursement rate for similar tests is in the $45 to $47 range.

In December SpeeDx established a US subsidiary to identify distribution partners in the clinical, research, and private pathology spaces. According to Denver, the firm has also begun integrating a distribution model that supplements its direct sales team in the US.

Harwood pointed out that in the era of antimicrobial resistance, "it is important to identify patients who have resistant strains so that treatment can be targeted and therefore reduce the possibility of serious" consequences for infected individuals. According to Harwood, the test's ease of use would allow it to easily fit into the laboratory's workflow if it is eventually developed into an automated assay.

However, Read noted that using the assay in the clinical and private pathology spaces does have immediate limitations. The "paradox" he said, is that as the incidence of antibiotic resistance rises, the cost benefit for SpeeDx’s test goes down. "I see this test as being clinically valuable in populations where resistance is found in 10 to 70 percent [of test cases], but cost-benefit [studies] are needed to establish this."  

SpeeDx indeed plans to perform cost-benefit and economic studies on the ResistancePlus MG assay in the US market, looking at the value in reducing different treatment failures. Denver expects to have data on the studies in 2019 if not earlier. In addition, the firm will launch its gonorrhea assay in July or early August, initially seeking approval for the assay in the European and Australian markets before switching to the US.

"We will then follow a similar model with our gonorrhea product that the M. genitalium assay is going through in the US market," Denver said.