Epigenomics plans to file its blood-based diagnostic for colorectal cancer, Epi proColon, for US approval before the end of the year, based on results from a 300-patient trial released last week.
The company is confident of the test’s chances with the FDA, claiming that it can save the healthcare system cash – but lingering questions over specificity, as well as cost, will make US registration an uphill struggle. Epigenomics’s CFO and acting CEO, Thomas Taapken, brushes these concerns aside, saying that “the specificity issue will not be such a concern to the FDA”.
The gold standard for diagnosing colorectal cancer is colonoscopy. This works extremely well, but it is expensive and extremely uncomfortable, so much so that only around half of those eligible for free screening with colonoscopy take the offer up.
The current alternatives include faecal occult blood testing and faecal immunochemical testing (FIT), which, though cheaper and not uncomfortable, are certainly unpleasant, and far less accurate than colonoscopy. Epigenomics wants to position its test here.
The latest trial of Epi proColon was a head-to-head study requested by the FDA to support a premarket approval application (PMA). It was designed, on the agency’s orders, to prove the non-inferiority of Epi proColon to Eiken’s OC-Sensor FIT test, and this benchmark was met as far as sensitivity goes; Epi proColon detected 71% of colorectal cancer cases whereas OC-sensor only caught 67%.
But the problem is – as it has always been – false positives. Specificity was determined to be 81% with Epi proColon, meaning that 19% of the cases it flagged as cancer were in fact clear. Specificity with FIT was much higher at 98%.
Epigenomics is trying to spin this disappointing figure as ambiguous. Mr Taapken tells EP Vantage that while “it’s obvious” that the difference between the specificities of FIT and Epi proColon “was quite large”, there was “overlap in the error bar, so it’s statistically inconclusive”.
This specificity figure, inconclusive or not, is surely unlikely to convince the FDA that the test is worthy of approval. But Mr Taapken insists that the crucial measure is sensitivity. “The really important thing in our view was to demonstrate non-inferiority with respect to sensitivity," he says.
“If you have a test which would lead to a major medical intervention then of course specificity would become much more of an issue and would be scrutinised by the FDA. In our case, and also for FIT, a positive result would trigger patients to be sent for colonoscopy, which at the moment is recommended anyway for colorectal cancer screening.”
This argument might convince if the test cost a few dollars. But Epi proColon is priced at $150 a pop, which is a lot to spend just to send patients with a positive result – one in five of whom have been flagged wrongly – to get a procedure they should have undergone anyway.
This is true of FIT too, but this costs just $30 per patient and almost all those it sends to colonoscopy do indeed have cancer.
Epigenomics claims that the price is justified as it can detect earlier-stage cancers better than FIT, and because it “drives awareness” of colorectal cancer screening.
“In the US every year about $14bn in healthcare costs is attributed to colorectal cancer. The reason for this high figure and the mortality of colorectal cancer is the fact that people just don’t get screened,” Mr Taapken says. He contends that if patients underwent screening more early cases, which have a five-year survival rate of up to 90%, would be caught, avoiding late-stage costs of the disease.
The cost-effectiveness argument comes after approval, and that hurdle must be cleared first. The FDA’s decision will, however, affect more than just Epigenomics: the company has licensed the biomarker its test detects, septin 9, to Abbott, which is separately developing its own version of the diagnostic. It has also granted Qiagen an option to a licence. Both companies would have to get independent FDA approval for their products, but the recent data could be used as part of those submissions, Mr Taapken explains.
“We know that Abbott have been watching the situation. When we came out with our pivotal data at the end of last year and announced the necessity of an additional study that the FDA imposed on us, Abbott took the approach to wait for this data to be generated by us."
“We assume that Abbott will, with this data in hand, be able to decide themselves whether or not they want to go forward with an approval in the US. We expect that at some point they will do that.” Abbott, however, has been conspicuously silent on the subject.
With the company’s competitor Exact Sciences in late-stage development with its faeces-based biomarker diagnostic Cologuard, and planning to file next year, Epigenomics must move fast (Event – Exact Sciences goes deep with Cologuard, November 26, 2012).
Any company that can develop an accurate blood test that can be used to screen for colorectal cancer will corner the market. Results of the recent trial suggest that Epigenomics is not that company.
|Epi proColon head to head vs FIT||NCT01580540|