NEW YORK – Singaporean molecular diagnostics company MirXes believes the results of a new clinical validation study will lead to wide uptake of GastroClear, its blood-based quantitative PCR test for the detection of gastric or stomach cancer.
The company's test measures 12 microRNAs – 11 biomarkers and one reference – in serum, and has a turnaround time of about three hours. The GastroClear assay underwent clinical validation at three centers in Singapore and 5,248 patients were ultimately screened using the test. Investigators claimed the test was able to detect 87 percent of gastric cancers, including 87.5 percent of patients with stage I cancers. The results were published last month in the journal Gut.
For MirXes, the results of the study are an achievement not only for its test, but for all developers of miRNA-based diagnostics, according to the company's CEO.
"It's a very significant step for us as well as for the entire microRNA field, as I don't think there has been any other miRNA test that has undergone a three-year prospective study at a scale of 5,000 plus people in a prospective fashion," said MiRxes CEO Lihan Zhou. "This is by far the most extensive miRNA clinical study there has been," Zhou said. "It's a huge step for us."
Scientists from Singapore's National University Hospital led the clinical validation study together with MiRxes, which is headquartered in the country's Biopolis. Other participating institutions included the National University of Singapore; the Agency for Science, Technology, and Research (A*STAR); Diagnostics Development Hub (DxD Hub), a Singaporean initiative that supports diagnostic device development; and clinicians from Singapore's National University Health System. The Yonsei Cancer Center in South Korea also contributed.
The history of GastroClear stretches back close to a decade. From a discovery panel of close to 600 markers, scientists eventually selected a dozen for the final test. "Twelve markers also fit neatly into a PCR plate," noted Zhou.
All of the work was done using an in-house, high-throughput qPCR platform. Zhou said the company's lab in Singapore can run as many as 200,000 qPCR reactions a day, an ideal set up for discovery.
"We don't need to run microarray, we don't need to run [next-generation sequencing] because we have the throughput for discovery," he said. Because of its setup, he claimed that MiRxes doesn't have a "platform migration issue," as opposed to those who do discovery on sequencing platforms and migrate the results to qPCR.
MiRxes' assay was then validated with partners, and test performance was confirmed with endoscopy findings as well as biopsies. MiRxes and its partners are now positioning GastroClear as a screen for patients before endoscopy, Zhou noted, rather than a replacement test. The next step is to move the test into a community setting where it can be used to screen not only symptomatic patients, but also asymptomatic patients belonging to high-risk groups.
Calvin Koh, a consultant in the division of gastroenterology and hepatology at Singapore's National University Hospital and a coauthor on the paper, said that deploying the test in the country is underway.
"There is a plan for evaluation of this test in the primary care setting to monitor its effectiveness," Koh said via email. He noted that since the test received approval from the Singapore Health Science Authority last year, it can already be used in both primary care and hospital settings.
One question adopters will no doubt want an answer for is how the GastroClear test stacks up against endoscopy. As part of the study, the authors carried out a health economic analysis. Based on their model screening, GastroClear could increase early-stage detection rates to 40 out of 100 cancers diagnosed, versus 30 per 100 using current methods. Given this higher diagnostic yield, Koh said the test is cost-effective for screening in higher risk groups.
"The test is cheaper than endoscopy, but it is not an alternative to endoscopic therapy evaluation," said Koh. "It is a useful test for some patients who are at risk of gastric cancer but not willing to immediately subject themselves to endoscopy," he said. He added that costs are often contextual to the local healthcare systems. In the US, the average cost of an endoscopy is $912, according to medicare.gov, the government's official website for Medicare. The cost Mirxes' test was estimated at $175 for the analysis, but is being made available for $150 to customers in Singapore, he said.
As part of its assessment, Koh and colleagues also compared MiRxes' 12 markers to other biomarkers for gastric cancer in the test, including carcinoembryonic antigen (CEA), carbohydrate associated antigen 19–9 (CA19-9), anti-Helicobacter pylori IgG, and pepsinogens 1 and 2 (PG 1 and PG 2). Koh said that based on their analysis, the 12-miRNA assay "performed significantly better than any of the conventional blood-based biomarker tests."
However, he cautioned, those other tests only are about 60 percent sensitive for gastric cancer.
The Asian market
MiRxes obtained a CE-IVD mark for GastroClear in 2017 but has not sold the test widely to date although initial sales have surprised management.
"The adoption of the test started toward the second half of last year in Singapore and China," said Zhou. "We sold 6,000 tests within a few months and that was actually better than what we thought," he said. "People buy the idea because there hasn't been any new cancer stomach biomarker commercialized for a very long time," Zhou added.
After gaining regulatory approval in Singapore last year, the company has set its sights on expanding sales to China and Japan, where the test has been available for clinical research. Zhou said that studies are underway in both countries that should support future regulatory submissions. MiRxes anticipates its test could be available clinically in both markets by 2022.
Asia is the immediate target for GastroClear, as the incidence of gastric cancer is higher there than in European or North American populations. While gastric cancer is the fifth-leading cancer worldwide, according to the World Cancer Research Fund, the countries with the highest incidence are mostly in Asia, with the top 5 being South Korea, Mongolia, Japan, China, and Bhutan.
Because of this, GastroClear will be a "flagship product in Asia" for Mirxes, Zhou said, though a market also exists in South America, which also has a higher incidence of the disease. Every market is different, though, and while Japan and China suffer equally from the disease, their approaches to adopting new tests differ, with Chinese labs quicker to adopt new diagnostics, while Japan remains true to its by-the-book, conservative image.
"I think in China, everything is faster," said Zhou. "In Japan, people understand miRNA better, but getting things moving is a lot slower," he said. "It takes more time for them to adopt anything new.
For adjacent markets, such as South Korea, Zhou said that market entry will depend on identifying suitable laboratory partners and distributors. MiRxes is building its footprint worldwide to support the roll out of its tests. Earlier this year, the company established a Japanese subsidiary in Tokyo. It already maintained a manufacturing and R&D facility in Hangzhou, China, as well as a clinical lab in Tianjin.
In the US, the company recently hired Larbi Gallagher as its vice president of strategy and growth operations and is assembling a US sales team. Gallagher previously was head of commercial operations for Greater China for Illumina. Initial hires in the US will be in Chicago and Boston to serve the local pharmaceutical and biopharmaceutical markets, with a later expansion to California planned.
Zhou said that, overall, the company currently employs 110 people across Singapore, Japan, China, and the US. By the beginning of 2021, MiRxes should employ about 160 people, he said.
MiRxes is also raising money to support its growth. On top of a seed round of about $3 million in 2016, followed by a $40 million Series A round in 2018, the company is planning another round of financing. Zhou noted that the company is generating revenue via sales of its tests, even as it looks to raise more money.
The COVID experience
Like essentially all test makers, the ongoing COVID-19 pandemic has had an impact on MiRxes. Earlier this year, Singapore's Health Sciences Authority cleared a real-time PCR assay developed by A*STAR and partners, including MiRxes for SARS-CoV-2, with Mirxes responsible for manufacturing the test. In May, Los Angeles-based Cedars-Sinai Medical Center obtained Emergency Use Authorization from the US Food and Drug Administration to offer the test clinically.
According to Zhou, the company has shipped 5.5 million tests globally since then.
"It was a huge adrenaline rush," Zhou said of the experience. "We didn't know how many tests to produce," he said. "Nobody knew this thing would drag on so long and didn't seem to end."
What those sales – throughout Asia, but also in the US and in New Zealand – has also served as a gateway for winning over new customers, he noted. "The level of trust we established with many of these national labs is, I believe, the best benefit that COVID-19 brought to our company," he said.
MiRxes and collaborators are now developing a new test that combines SARS-CoV-2 with influenza. Zhou said the test would be submitted for CE-IVD in Europe and EUA in the US this month.