The U.S. Centers for Medicare & Medicaid Services (CMS) has determined that the time has come to offer Medicare coverage for blood-based in vitro diagnostics as a screening tool for colorectal cancer (CRC), but there’s one catch: At present, there is no such test approved by the FDA that qualifies under the terms of the coverage memo, making this a null coverage proposition, at least for the time being.

The CMS posted the final coverage memo with the requirement that tests are covered only for those aged 50-85 years, assuming they are asymptomatic and at average risk of developing CRC. Any qualifying blood-based biomarker screening test must offer at least 74% sensitivity and no less than 90% specificity compared to colonoscopy. The term “average risk” is defined in part by no personal or family history of the disease, but also as no personal history of Crohn’s disease or ulcerative colitis. Any qualifying test will be covered only once every three years, which was the frequency of testing spelled out in the draft national coverage determination (NCD).

However, CMS acknowledged that at the time of the publication of the final coverage memo, the Epi Procolon test by San Diego-based Epigenomics Inc., is the only FDA-approved or cleared test for screening purposes. The problem for the Epigenomics test is that it “does not meet the criteria” spelled out in the final coverage memo, the agency said. Consequently, the agency declared it “will non-cover” the test, apparently tying the hands of Medicare administrative contractors who may want to cover the test as other test developers get their products through the appropriate FDA premarket review mechanism. Ironically, it was Epigenomics that requested that the CMS undertake a national coverage analysis for this purpose.

Jorge Garces, the company’s president and chief scientific officer, said in the request that the Epi Procolon was already not covered by Medicare for screening, but added that screening with the company’s test yields benefits that are similar to the other covered screening methods. However, the procedural harms associated with a blood draw are substantially less than those incurred in colonoscopy, but Garces said annual screening would be the ideal interval for the company’s test.

Task force/medical society mandate stripped from final

The draft coverage memo required that any covered test be include as a recommended screening test by at least one medical society guideline or consensus statement, or alternatively enjoy an endorsement by the U.S. Preventive Services Task Force (USPSTF). This provision, which did not find its way into the final, notes that screening protocols are perhaps the principle driver of falling mortality rates over the past two decades. Compliance with screening recommendations in 2018 was greatest among those aged 65-75 years at 79.2%, while compliance for those aged 50-64 was 63.3%.

CMS said that while the Epigenomics test was the only test authorized by the FDA for screening, several other tests are in development, some of which use blood-based markers other than the Septin 9 gene used in the Epigenomics test.

Cynthia Bens, senior vice president for public policy at the Personalized Medicine Coalition, recommended that CMS lower the age of eligibility to 45 years, while Chandra Branham, vice president for payment police at the Advanced Medical Technology Association, did not differ with the proposed sensitivity and specificity thresholds. However, Karen Weck, president of the Association for Molecular Pathology (AMP), recommended that the NCD carry the sensitivity and specificity benchmarks allowed by any FDA-approved labeling for an approved test. Weck said officers in the CMS Coverage and Analysis Group (CAG) were outside their area of expertise in determining these thresholds, but AMP backed the draft’s requirement of inclusion of a test in a medical society or USPSTF recommendation.

Patient group surprised at exclusion of Epigenomics test

Michael Sapienza, CEO of the Colorectal Cancer Alliance (CCA), told BioWorld that the alliance is “encouraged and excited that the evidence is sufficient to cover” such a test. However, Sapienza said he found it a little surprising that CMS determined that the Epi Procolon does not perform adequately to meet the needs of a screening test. “There are studies that demonstrate that this is a very, very effective test,” he said, adding that the three-year interval between covered tests is likewise difficult to comprehend.

A blood-based test could drastically change the effort to bring colorectal cancer under control, particularly given the beneficial effect on compliance with screening guidelines. However, Sapienza said this is particularly the case for those aged 45-59, “where we’re having the hardest time getting people screened.” He said that communities of color are also populations that would benefit greatly with coverage. Sapienza said the CMS is perhaps being cautious with the Epigenomics test, given that the associated marker is the first to commercially emerge in connection with screening, but he argued that there are studies that demonstrate that the Epi Procolon outperforms the Cologuard test by Exact Sciences Corp., of Madison, Wis., depending on the model used.

David Bull, director of marketing for Epigenomics, said CMS arrived at the cited sensitivity and specificity set points by looking at the sensitivity of fecal immunohistochemistry, the specificity of the Cologuard, and an additional parameter, the three-year interval of coverage for the Cologuard test. Bull said a wide range of medical organizations had discouraged CMS from listing required performance parameters, adding that the agency’s view of the performance of the Epi Pro Colon was derived from a comparative microsimulation model.

While the Epigenomics test does not meet the requirements spelled out in the final coverage memo, Bull said a comparison model published by the National Cancer Institute demonstrated that the Epi Procolon was superior to fecal immunohistochemical tests and the Cologuard, which are both CMS-covered methods. “In fact, the conclusion was Epi Procolon is the ‘test of choice’ for patients who refuse colonoscopy – better than both FIT and Cologuard,” he said.

Bull noted that most of those who commented on the draft NCD had discouraged the requirement of medical society/USPSTF guideline inclusion, mechanisms he said are not particularly conducive to coverage of breakthrough technologies. He noted also that unique aspect of a test for Septin 9 is that it is directed toward patients who are unwilling or unable to complete a colonoscopy or stool test. “This directly addresses the pervasive challenge that one in three Americans remain unscreened for colorectal cancer,” Bull said. Despite the outcome, he said Epigenomics intends to engage in a multi-faceted approach to achieving Medicare coverage.