NEW YORK (GenomeWeb) – Despite setbacks in recent years, diagnostics firm Epigenomics continues to push for clinical adoption and reimbursement of its colorectal cancer screening test Epi proColon, hoping to cement its position in the blood-based detection market at a time when a number of new companies have begun to stake claims but few have yet proved their technologies in the clinic.
Among recent milestones, the firm has launched a kit version of the epigenomic test technology behind Epi proColon, announcing the product last month.
The company has also been working on a variety of clinical utility studies, trying to measure the impact its test can have when presented to specific groups — in the context of health fairs, in corporate settings, or in other workplaces — particularly in increasing the number of individuals who partake in colorectal cancer screening.
In the meantime, company investigators continue to advance other tests, refining the firm's existing Epi proLung assay and advancing a newer test for liver cancer, which researchers presented on at a company-sponsored workshop at the annual meeting of the Association for Molecular Pathology in November.
Epigenomics received FDA approval for Epi proColon — a blood based test that detects methylated SEPT9 DNA — in 2016, but has struggled to push the test into wider adoption.
For example, product revenues for the company in the third quarter of 2018 were up 73 percent over the same period in 2017, but were still only €283,000 ($322,766).
In an interview, Epigenomics' Director of Marketing David Bull confirmed that the company's expansion and reimbursement setbacks have stemmed, at least in part, from a US Preventive Services Task Force (USPSTF) decision several years ago to use what Epigenomics has said was outdated performance numbers for the test when updating its guidelines.
According to Bull, that issue has led to a "chicken and egg problem," in which the USPSTF decision has provided a rationale for other guidelines to similarly mischaracterize the test and hindering the company's ability to make a case for appropriate reimbursement.
"CMS has thrown [the company] a couple of curveballs," Bull said.
"In 2016 we had a miscellaneous code that we were using because we didn't have a CPT code. Then in 2017, they gave us a CPT code but at a very low reimbursement that was that was not indicative of other … parallel assays in the market, nor indicative of the effort and the cost to do the tests," he explained.
Following that, the decision was made to gapfill, a process in which a new reimbursement rate is calculated from an average of payment rates from Medicare contractors over a period of about a year.
But that, Bull said, meant that the test was listed without a price for all of 2018, hindering any potential decisions the company might have seen from private payors, who often match their reimbursement rate to Medicare's. Fortunately for Epigenomics, starting in 2019 the company will have a new code for the test at a price of $192.
Despite these practical challenges, Bull said that the company has remained dedicated to convincing the field of Epi proColon's utility. Since the assay was FDA approved, that has included a variety of studies focused on specific populations as a way of narrowing down the specific claim that the test, because it is performed on blood, can help increase the number of people being screened for colorectal cancer.
"For years, colorectal cancer has been plateaued at a 65 percent compliance rate in the United States, and the 35 percent who don't get screened are a tremendous source of both cost and mortality," Epigenomics CEO Gregory Hamilton said at the company's AMP workshop last month.
"That's not bad. That means two thirds of the people are getting screened," added Theo DeVos, director of development and commercial operations for Epigenomics in North America. "But what that really means is about 25 million Americans who should be getting screening or are eligible, who meet the criteria, are for many different reasons not actually getting colorectal cancer screening."
Add to that, he said, the fact that a majority of mortality is in the unscreened population. "Based on all of that then, the question really is how do we change the status quo," DeVos argued.
"We know colonoscopy is great. It works. We know "[Exact Sciences'] Cologuard works. It's a great test. We know FIT testing works. But for people who aren't doing it, none of them mean anything."
This, he said, is what Epigenomics hopes it can persuade payors it can offer. "If you're able to reach people who don't get screened for whatever reason … [and a test is] properly applied under the indications for our test which is 'unwilling and unable to be screened by other methods,' I think that you have a real opportunity to make a difference for those 25 million people."
The company has been working on studies that drill down into the why's of that 35 percent rate of unscreened patients. Some of the reasons that come up consistently, he said, are that the method itself is undesirable: an "ick factor."
"If you're really indigent, you don't have access to care, you don't have an address. These are barriers that make screening difficult," he noted. "You [also] may not be the person who thinks about screening because I'm not sick and I don't get sick. … and there are also settings, like in the Veterans Administration, where people largely do what they are told, but there is a subset … that simply refuse, and then finally in the corporate setting where everybody is busy [and] we don't have time."
"We've looked at a lot of these things in a lot of different studies, mostly smaller clinical utility type studies, asking, 'If you have these challenges, would offering a blood test make a difference?'" DeVos said.
Most of the company's work in this vein is still ongoing, he added. But, he shared some early insights during the AMP presentation. In one study, organized around the question of accessibility, Epigenomics has been working with researchers at the University of Miami as part of a program of health fairs. Other methods have already been part of these fairs, but uptake has been very low.
"We came to an agreement that they would attempt to add SEPT9 testing, after first … offering other tests. So then, after people refused, saying, 'OK well then why don't you try this blood test.'"
For example, the health fairs had previously distributed 364 fecal testing kits, only 82 of which were returned. "Here you are seeing clearly people really don't get tested. And even if you give them a free testing opportunity, they don't use it. So, the question was in that setting if we had a blood test can we actually do something useful," DeVos said.
This has now been going on for a year, and the success has been high enough that it is now planning to do another year at the request of the U of Miami group, he added.
Analysis of uptake has been complicated, but DeVos reported that for a subset of patients where the group knew that the return rate for fecal tests has been only around 15 percent, Epigenomics saw over a fivefold increase in adoption with its blood test.
In a similar study in collaboration with investigators at the West Virginia University Cancer Center, the team has been offering the test in a program for women receiving mammography. "We are seeing them being very wiling to put out their arm and give blood, so that study is really showing promise," DeVos said.
In addition to these studies, another U of Miami team has has begun an effort to see if Epi proColon can increase screening among firefighters, and the company is studying uptake with the VA and in a corporate wellness context, with Molson Coors.
Pushing into 2019, Bull said that the firm is confident it can use data coming from these studies, and also leverage its new CPT code and $192 reimbursement price to drive the adoption that was stymied after its 2016 FDA approval.
The company isn't yet aggressively marketing the newly-launched BIS kit, which it premiered at AMP, he added. But the decision to create the kit may prove crucial if Epigenomics is successful in growing its test menu — offering customers a single platform that could potentially support not just Epi proColon, but also other tests with the same DNA extraction and conversion needs.
One of those could be a test for hepatocellular carcinoma, which the company also discussed at AMP, highlighting a European study that emerged from hypotheses that the same SEPT9 methylation that Epi proColon relies on might be a strong biomarker in liver cancers.
Abderrahim Oussalah from the University Hospital of Nancy in France reported he and his colleagues' initial study and a replication by German collaborators, which showed that measuring methylated SEPT9 showed high diagnostic accuracy with an area under the receiver operating characteristic curve of up to 0.94.
Hanley said during the meeting that the company had already initiated the steps to begin a 500-patient US replication study, and Bull said that the HCC application of the Epigenomics SEPT9 assay is already CE-marked for use in European labs.
"There is a huge need," he said, stemming from the limitations of current protein biomarkers used to monitor patients with liver cirrhosis for the emergence of cancer. According to Bull, the European study results were strong, but the firm still needs to confirm the results and do a more thorough exploration of different variables like whether patients' cirrhosis stems from a viral or lifestyle cause.
The company is also continuing to work on its Epi proLung test, including exploring whether that assay, similarly to the HCC test, could have utility in monitoring patients with a known risk, as well as looking to see if there are particular subtypes of patients in which it works better or worse as a cancer detection tool.
Since Epigenomics' FDA approval for the proColon test in 2016, multiple companies have announced their intentions to develop blood-based genomic and epigenomic assays for early cancer detection and monitoring, not just in colorectal cancer, but across the spectrum of solid tumors.
Startup firms receiving significant attention and/or garnering large investments include Grail and Freenome, as well as companies like Guardant Health, which are also seeking to translate their existing blood-based cancer genotyping technologies into the early detection and screening space.
Many companies are also focusing specifically on methylation, albeit with a broad genome-wide approach in contrast to the specific, defined biomarker strategy that is at the heart of Epigenomics' tests.
Others, like CellMax Life, are banking on technologies that detect the presence of blood-borne cancer cells.
According to Bull, Epigenomics feels confident in continuing to push forward its existing assays, considering how far from the market various potential competitors still remain. For the most part, he said, the companies receiving attention in the space have only presented data from case-control studies where detection of known cancer samples is compared to known controls. This is far from a demonstration in a true screening population.
"We would be silly to think that there's not going to be any competitors in the market for the rest of the lifecycle of [our] product. But what we're finding is that the FDA process is not easy, the CMS process is not easy … and any new entrants into the market are going to have to go through exactly what we went through."