COLVERA
My holiday reading lead me to discover that Dr Trevor Lockett (Executive - Technical Director of RHY) also contributed to the development of the recurring bowel cancer test 'Colvera' during his time at CSIRO. The test has been available in the US, in all 50 States since 2017, via the CLIA lab pathway. Clinical Genomics, located in New Jersey, who owns the technology, is not a publicly listed company. The test is not currently available in Australia. The test is a DNA/molecular blood test costing around $450. It is therefore not suitable for mass population screening.
From the CSIRO website -
"CSIRO, in collaboration with Flinders University and Australian-founded biotechnology company Clinical Genomics, identified DNA with cancer-specific chemical changes associated with bowel cancer which are not found in normal colon tissue. The team was able to show that some of these changes can be detected in the blood of patients with CRC, providing a reliable marker for detection of the disease.This discovery was used to develop a new innovation, known as Colvera™, a blood test which detects these cancer-specific chemical changes in fragments of DNA from the tumour found circulating in the blood. Clinical trials have shown Colvera™ to be more than twice as sensitive for CRC recurrence as the current CEA test.Clinical Genomics successfully launched Colvera™ in the US market in 2017. The test is currently available in the US through Clinical Genomics' laboratory in Bridgewater, New Jersey."
It seems that the product, although developed in Australia, is more suited to the US market and has specifically sought market penetration by forming a partnership with an American company. This is most likely driven by the traction potential of the CLIA lab pathway, which does not exist in Australia, and also because the test would be attractive to insurance companies as a monitoring test for CRC patients, a cheaper and less invasive alternative to colonoscopy. I'm guessing that the Australian market is too small to be of interest in the medium term.
It's reassuring to know that Dr Lockett has recent experience launching Colvera in the US, and from what I can tell, the collaboration succeeded in this pursuit via a CLIA lab within a competitive market for privately funded DNA-based CRC blood tests. Also interesting that TGA approval for the Australian market was bypassed. I guess the primary motivation is to maximise profits in a large market, remembering that Colvera is not suitable for mass population screening..
PAN-CANCER DETECTION (ADENOMAS)
This area is of great interest and very important in my opinion.
Firstly I read a detailed report by the US CMC (Medicare) organisation published in 2021 which outlines the reasons for rejecting Epi ProColon (DNA blood test costing around $300) for Medicare reimbursement. The main reason given was that the test had no advantage over the current standard FIT (poo) test in terms of detecting polyps and early stages. It cited that the FIT test achieves around 27% sensitivity for pan-cancerous lesions (adenomas) while Epi ProColon achieves around 22%.
https://www.cms.gov/MEDICARE-COVERAGE-DATABASE/view/ncacal-decision-memo.aspx?proposed=N&NCAId=299&type=Open&bc=AAgAAAAACAAA&
The report also details a range of very specific criteria that any future cancer blood-based population screening tests would need to meet in order to attract Medicare reimbursement.
Notably - "For the new blood-based CRC screening test, both sensitivity must be greater than or equal to 74% and specificity must be greater than or equal to 90%"
Colorguard (DNA fecal test around $500) is the only FDA-approved CRC test to also have Medicare reimbursement in the US, aside from the FIT (poo) test.
In this context, I then looked for information on the pan-cancerous abilities of Colostat. I was interested to re-read an interview of Glenn Gilbert (RHY CEO) in May 2022 by Alan Kohler
disallowed link/investment-news/rhythm-biosciences-set-to-debut-colon-cancer-blood-test/151311"Alan: What are the sensitivity and specificity numbers for the faecal test?
Glenn: They range, depending on what model you get. They can have a sensitivity of around 60-odd per cent, 60 to 80 per cent in some cases and their specificity ranges between 50-odd to 90 specificity.
Alan: That’s a big range.
Glenn: It is, and that’s some of the challenges you’ve got but we’ll have that uniform approach being a blood test, so we reduce that variability and people know what they’re getting. So, we’re more accurate than them by 35 per cent, than the faecal test as per our clinical trial results, which is great, and we’re more accurate than them at advanced adenomas, which is pre-cancerous, which is really, really exciting."
Glenn also says in this interview -
"Alan: And what’s going on in the United States?
Glen: It’s a really interesting space. The two main entry points that we’ll be going to is CLIA Lab, that’s a lab-developed test which does not require FDA approval and then of course, there is the FDA approval pathway. The CLIA Lab or the lab-developed test, that’s very common for a test like ours and most companies tend to find they live in that space because it’s such a lucrative opportunity. The labs that shareholders would expect us to be talking to and indeed we are, are the likes of Labcorp, Quest, and indeed, Sonic, they’ve got a very strong profile in the US, Mayo Clinic as well. So, there’s no need for an FDA approval in that pathway, we simply send our kit over to those particular laboratories, they independently validate it on their machinery, on their test machines that they have in their laboratories and we simply supply them the product and they run it as their own little business. Interestingly, the partner selection there is very important, whether we go a regional or a country-wide partner, like those large three or four, or whether you go for a more niche approach in particular states.
Alan: That seems exciting…Can you have multiple distributors?
Glenn: Not via a CLIA Lab, but some of those laboratories have multiple licences, if you will, and approvals to having multiple states, so it would be favourable to go with one of the larger companies providing they’ll give ColoSTAT the love it deserves.Indeed.
Alan: So, why would you get FDA approval if you don’t need it?
Glenn: Correct, and that’s a common question. I guess, FDA approval gives it the benefit of all but guaranteed a reimbursement by the CMS and that’s the main reason why you look at that. It would also arguably help to get on the guidelines for…
Alan: What’s the CMS?
Glenn: Centre of Medicaid Services, that’s your Medicaid/Medicare programs over in the US.
Alan: Can you get reimbursement from CMS without FDA approval?
Glenn: You can and also via the private health insurers, to the Medibank and Bupas of the world over there like United Health, for example.
Alan: Do doctors prescribe the test without FDA approval? Is that the way it works? I’m just wondering what the difference is between FDA approval and not?
Glenn: They can. The FDA approval, as I mentioned, guarantees a CMS or the reimbursement pathway and it also gives stronger benefit to get onto the guidelines for screening programs. But if you have a strong enough demand, as we expect we would with our offering, that should be attractive even without FDA approval.
Alan: I just find it fascinating that you can sell these things in the US without FDA approval.
Glenn: The lab does take on a lot of the responsibility for that. Part of that independent validation, they’ve got post-market surveillance systems in place, they’ve got recall systems in place, they’ve got all the infrastructure that one would need to be able to perform that job. I’m making it sound more simplistic than it is, but there’s a lot of management that goes around these tests."
And -
"Alan: What do you reckon? Start with the cost, what are they going to cost you to make?
Glenn: We’ve taken an approach where we’ve got a $50 price in our presentations and so that gives the market, the major five regions, a $38 billion global addressable market. There’s some channels that, like we discussed earlier, the health insurers that may pay a bit more for that so there’s potential upside. Some analysts are looking at around that $40 to $60 price point that we would sell it for."
Thought I'd share my (albeit adhock) research here for interest's sake, and to potentially inspire others to look further. I welcome any constructive comments.
(20min delay)