NEW YORK – Gastrointestinal health diagnostics company Geneoscopy is one clinical trial away from gaining final regulatory approval for its at-home stool-sample diagnostic test for colorectal cancer and presenting consumers with an option besides Exact Sciences' Cologuard.
The company — which was cofounded in 2015 by Washington University in St. Louis researchers Erica Barnell and Yiming Kang and Wharton MBA Andrew Barnell (Erica's brother) through the WashU School of Medicine's entrepreneurial incubator SlingHealth — is positioning its test as a direct competitor to Cologuard. But instead of looking for DNA biomarkers in stool, Geneoscopy's multifactor assay combines eight stool-derived eukaryotic RNA biomarkers, patient demographic information such as smoking status, and a fecal immunochemical test, or FIT, to detect cancerous lesions.
According to CSO Erica Barnell, the focus on RNA rather than DNA makes Geneoscopy's test much better than Cologuard at detecting the high-risk adenomas, or HRAs, that are most dangerous to patients, given their high malignancy transformation rates of up to 30 percent to 50 percent per year.
The studies the company has conducted so far would seem to bear that out. A 2019 study of 275 people published in Gastroenterology by researchers at Geneoscopy and WashU found that the company's test attained 91 percent sensitivity for detecting colorectal cancer, or CRC; 73 percent sensitivity for detecting HRAs; and 89 percent specificity for all other findings, such as medium-risk adenomas, low-risk adenomas, and benign polyps.
The researchers noted in that paper that the improved sensitivity was attributable to Geneoscopy's use of stool-derived eukaryotic RNA, or seRNA, biomarkers.
"First, seRNA biomarkers are derived from epithelial cells shed within the gastrointestinal tract. Therefore, the signal of the seRNA represents a homogenized sampling of the perilesional tissue, which is preferentially shed into the lumen and excreted in stool," they wrote at the time. "Second, seRNA provides a concentrated and amplified signal that can be observed across multiple transcripts in a single pathway. This is a direct advantage over DNA-based biomarkers, which are limited to two copies per cell."
They also found that the transcriptome provided them with a look at the downstream effects of many precancerous variants, regardless of the tumorigenesis pathway, and that a relatively small panel of seRNA biomarkers encapsulated the larger genomic landscape of mutations that cause adenoma development.
The firm's more recent study, published in Clinical and Translational Gastroenterology in May, looked at the test's ability to detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. The cohort was also supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with HRAs or CRC before treatment or resection.
This study found that the RNA-FIT test had 95 percent sensitivity for detecting CRC and 62 percent sensitivity for detecting HRAs.
But while Cologuard has a comparable 92 percent sensitivity for detecting CRC, it only has 42 percent sensitivity for detecting HRAs.
Geneoscopy's previous findings were enough to get the US Food and Drug Administration to grant the company diagnostic Breakthrough Device Designation in January 2020.
"We anticipate that this will be the final assay that we will be achieving FDA approval for. The data from this study will support a [premarket approval] application to the FDA," Barnell said. "And given the Breakthrough Device Designation, we are expecting rapid approval or expedited approval of our diagnostic."
She also noted that the Breakthrough Device Designation was awarded based specifically on the assay's sensitivity for detecting advanced adenomas.
This week, the company began enrolling patients in CRC-PREVENT, what it believes will be the pivotal trial evaluating the test's safety and efficacy in average-risk individuals with no known comorbidities associated with cancer risk.
The prospective, single-arm study will eventually enroll more than 12,000 patients across all 48 contiguous states in the US. Patients will submit their samples through the mail and will subsequently undergo optical colonoscopies. All significant lesions discovered during the colonoscopies will be biopsied or removed and sent for histopathology. Researchers will then conduct a comparative analysis to determine sensitivity and specificity for colorectal cancer, advanced adenomas, non-advanced adenomas, benign hyperplastic polyps, and colonoscopies without findings.
The company is aiming to complete the trial in early 2022 and is hoping to receive FDA approval not long after its regulatory submission, though final approval ultimately depends on the agency's priorities. It's planning to pursue approval for an intended-use population of average-risk individuals, ages 45 to 75. At some point in the future, the company is also considering pursuing additional approvals or amended approvals for high-risk patients as well as patients with comorbidities or those who have predispositions that prevent them from getting colonoscopies.
"The intended use population here is the same as Cologuard," said Geneoscopy CEO Andrew Barnell. "The patient population that Cologuard is serving right now is exactly the intended-use population that we will be approved for. When we talk about identifying high-risk patients, we're trying to identify those patients that have advanced adenomas, and navigating them to colonoscopy."
Erica Barnell also noted that even average-risk asymptomatic patients have an incidence of about 7 percent to 9 percent of advanced adenomas. "So, those lesions are really important to be able to detect so that you can remove them and eliminate the possibility for those individuals of developing a cancer," she said.
The company has also started speaking to the Centers for Medicare and Medicaid Services, as well as private insurance companies, to discuss coverage for the test once it's approved. Those talks are still in the early stages, Andrew Barnell said, noting that most payors want to see final test data before they agree to cover an assay. CMS, he added, has a mandate to cover only FDA-approved tests.
"But we've absolutely had preliminary conversations with both government and commercial payors. And I think the nice thing about our field is — partly driven by Cologuard and Exact Sciences and partly driven by the huge unmet need and the need for more screening in colorectal cancer — all of them are very aware of this testing category," he said. "All of the insurers want to cover more tests. They want more accurate diagnostic tests for the space. They want ones that are in blood and stool, to cover the whole spectrum. So we've heard, so far, a lot of excitement. But, to a certain extent, some of it has to wait until we have the data."
Erica Barnell also noted that both the FDA and CMS have expressed enthusiasm about the new study's intended patient population. Because of the recruiting tactic Geneoscopy is employing, the company is signing up more patients from rural areas and patients from populations that are traditionally underserved. The outcome, she added, will hopefully be more representative of the intended-use population than a traditional clinical trial.
Being able to put the test on the market isn't the only exciting part of having gotten this clinical trial off the ground for Erica Barnell. Now that the CRC indication is almost a commercial reality, she can divert her focus to applying Geneoscopy's technology to the development of tests for inflammatory bowel disease, or IBD, irritable bowel syndrome, and other diseases of the gut.
"When we started looking at the pipeline products and patients with other indications, we started looking at novel approaches, which we have the capabilities of doing in the RNA space," she said. "Some of the things that I've been working on is not just looking at the host enterocytes, or the cells that line the gut, but also looking at lymphocytes, looking at the immune system, looking at various mRNA transcripts that are associated with all the tissue in the gut, not just the epithelial cells. I think that plays a very important role in allowing us to help patients specifically with IBD or inflammatory and autoimmune conditions."
The company is also partnering with other firms in the field to develop assays for patients with gastrointestinal disease, and is planning to make some announcements in the next couple of months regarding its pipeline products.