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  • Is Exact Sciences Poised For A Monopoly On Colon Cancer Screening? [View article]
    Epigenomics test failed at the FDA. The reason it failed was pretty simple, it has performance somewhat similar to FIT (a little worse actually) and it will be much more expensive. Therefore, it is a decidedly inferior test to FIT from the point of view of economics. Everyone, however, wants to see screening increased for colorectal cancer. Therefore, the FDA decided that if EPI could increase screening compliance over FIT that would provide evidence that might make approval feasible. On the other hand, the peer-reviewed data from the largest trial run on their test was pretty unconvincing, while they claimed to have improved the test it does not have strong performance and it is impossible to compare to Cologuard since the full data set, including performance with regards to adenoma type is lacking in peer-reviewed literature. However, it is a very safe bet that Epi's test will be significantly inferior with regards to detection of the most dangerous adenomas. When this occurs who would recommend an inferior blood test over a much superior stool test?

    The other tests mentioned in this thread such as Chek-cap and the blood mononuclear cell gene marker tests have so little data published in the peer-reviewed literature that it is impossible to draw performance comparisons to a the 10K subject prospective trial performed by Exact Sciences. However, it is probably incorrect to characterize the position of Exact as being a monopoly. But what is true is that for the near term future (say 5-10 years) they will have a monopoly on the market for physicians and subjects who worry about the performance characteristics of the test. I don't think it is appropriate to go into all the science in a comments thread, but I don't see any evidence that these other non-invasive tests will come close to approaching the performance of Cologuard for both pre-cancerous adenomas or the more dangerous flat, serrated adenomas.

    When the USPSTF comes out with an A or even B level recommendation for Cologuard later this year, then all the private insurers in most states will be obligated to reimburse for Cologuard in the non-Medicare population. When this occurs, every doctor and screen-eligible subject who refuses colonoscopy will have to ask if they are content to go with inferior tests when Cologuard is relatively simple and safe. I think the answer will be no and the other tests will be relegated to very small niche markets in the US. FIT will likely continue to sell in poorer countries where cost is paramount.
    Feb 17, 2015. 06:29 PM | 4 Likes Like |Link to Comment
  • Epigenomics AG Vs. Exact Sciences: Who Wins The CRC Early Detection Fight? [View article]
    You may be right about the test. However, when you have a test that is quite expensive and it has inferior performance to its cheaper competitor, then you are really going to have to prove that it will increase compliance. Nothing done in 178 subjects will suffice since you will have to convince the FDA that it would increase compliance in a real-world setting. I think their best chance would be to piggy-back on all the other tests that are performed when you give blood at your doctor's office. The question in this case would be is there enough sample and would it be reimbursed in this setting? What I really worry about with this test is that it would parallel what's been found with FIT/FOBT. Those tests should be performed with a yearly interval - however when you get a negative result (as most results are) your natural tendency is to relax and not go the next year (this phenomenon has been shown in numerous very large scale trials where compliance can be over 70% in year one, and then drops to less than 15% in year 3). This test is too expensive to be used yearly. So unless there is a dramatic drop in price....
    But I wouldn't say it is impossible.
    Jun 5, 2014. 01:05 PM | 1 Like Like |Link to Comment
  • Epigenomics AG Vs. Exact Sciences: Who Wins The CRC Early Detection Fight? [View article]
    This was predictable. The test is inferior to FIT at a much inflated price. I don't think it will increase compliance. Long before I invested in this space I did some DD about fecal blood testing. I found that there were many health care organizations where use of FOBT was very low. I asked the officers why and I was told "Most of our physicians think FOBT is worthless, and hence they advocate for sigs or colos". A number of officials didn't seem to know the difference between FOBT and FIT. So now you have this inferior test to FIT and you really think PCPs will be banging down the door to recommend it to their patients when Cologuard is available? Not likely. Further, this test is way too expensive. Any well-performed cost analysis will find this test dominated by every other test. This is exactly the type of medical diagnostic you want to keep OUT of the market. It will drive up health care costs at great expense compared to much better (Cologuard) or somewhat better and cheaper (FIT) non-invasive options.

    Performing a trial to figure out how this will increase compliance seems to me a daunting task. In order to get a real-world, believable, answer I would think it will take many thousands of subjects and at least three years. It will be interesting to see how such a trial would be designed. Anything with fewer than, I would think, around 10K subjects would not be generalizable, in my opinion.
    Jun 4, 2014. 11:36 AM | Likes Like |Link to Comment
  • EXAS: Testing Negative For Future Revenue [View article]
    I really appreciate you backing up your arguments with facts and links rather than the vituperative comments that don't engender discussion.

    You can't possibly compare the price of CTC to Cologuard. The calculations CMS performed were based upon the assumption (i.e. $488 ) that CTC would cost as much as colonoscopy (which at the time was reimbursed as $500 and $650 with polypectomy). With co-pays that price is significantly higher. The problem with CTC was the recommended screening interval was too short (5 years) to be non-dominated. The real question for Exact is what will the total reimbursement be. Don't forget that as pointed out by another commentator, there is a 15 year period between 50-65 before Medicare payments kick in. There are also issues of non-medical costs (i.e. lost work, ability to work day of procedure etc.) that can significantly impact overall costs. Numerous papers discuss these issues. All of this however is irrelevant on some level to the main question. Since CMS decided to not cover CTC, and you claim this is equally costly, then the only conclusion one can draw from your argument is that CMS will like-wise not cover Cologuard. Do you really think this will be the case? You claim that is a probable outcome, but you are saying this on the basis of almost zero information since the arguments for CTC cost were based upon well-established CT procedures with long reimbursement histories. This is a completely new product. Therefore, the only important question is what will the overall reimbursement be.

    As far as modeling SSA's maybe you have worked with these models, however you maybe haven't read the models in details. There are a huge number of assumptions in these models involved in the natural history of the progressions. All the models you reference include assumptions about all CRCs arising from adenomas. It is a simple thing to modify the assumptions to include data on SSAs and rerun the model. As a matter of fact, the models are updated regularly. For instance, the SimCRC model model allows for heterogeneity in growth and progression rates across multiple adenomas within an individual. This is an easy parameter to tweak for incorporation of SSAs and the sensitivities to SSAs for FIT and Cologuard. Unfortunately, there is probably not enough good data on the lack of detection of SSAs in many colonoscopies to include this, but certainly it could also be included as an adjustable parameter. It is true that sDNA was well past the efficient frontier of FIT as studied in the most recent paper (but before the data from Cologuard) http://1.usa.gov/1rJTtVe
    However, adjusting the adherence rates and overall performance showed that with improvements, many of which Cologuard and Exact may make, this test can be pushed onto the efficient frontier as shown by simulations in the paper. Further, that paper also makes some unrealistic assumptions about adherence to fecal blood testing.
    In short, you make a weak argument from this perspective that these models can't incorporate SSA data.

    Lots of DNA screening tests are now covered by Medicaid including all the pre-natal tests from Sequenom and Verinata and Ariosa for aneuploidy. Therefore your blanket statement that "It is HHS policy to explicitly not allow genetic tests to be used for screening among asymptomatic patients" is simply not true. On today's cc the CEO claimed he was quite confident that there would be a cross-walk approach used. So an investor has to believe your biased (large short position) opinion versus that of the biased CEO (long) who has quite a few more legal ramifications to what he says on a conference call than you do on a web site. This is not to say you might not be right. But, certainly, Conroy has way more information vis a vis the CMS thinking and discussions than you do. Therefore, when he says this publicly on a CC I think this has weight.
    May 1, 2014. 03:39 PM | 2 Likes Like |Link to Comment
  • EXAS: Testing Negative For Future Revenue [View article]
    Almost every assumption and conclusion here can be strongly questioned. Kudos for a well-researched article, It's nice to see a well argued thesis. Since to rebut every point would take as long as the original, I’ll start by responding to a few.

    When CMS decided to not reimburse CTC, they did it based on price, as you suggest, but it was never explicitly stated. The real reason, which I heard from someone on the panel, was that it cost almost as much as a screening colonoscopy and since a positive would lead to a referral for a optical colo anyway, it was deemed cost ineffective. Had the price been significantly cheaper it would likely have been approved. Cologuard is significantly cheaper.

    You quoted CMS as stating "The Social Security Act provides that no Medicare payment may be made for expenses incurred for items or services that are not reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member. Consistent with this, Medicare does not pay for preventive screening tests except for those specifically authorized by statute (e.g., prostate-specific antigen test).” What you conveniently neglected to point out is that, like a PSA test, colorectal cancer screening is specifically authorized by statute for approved tests like colonoscopy fecal blood and sigmoidoscopy. So, the only way your conclusion is valid is if you think CMS will not endorse reimbursement of Cologuard like it did for CTC.

    The calculation of cost-effectiveness is very tricky and relies upon numerous assumptions. The previously commissioned CMS study you reference is old (2007). One problem that bedevils all the comparisons to FIT, and indeed even to colonoscopy, is that Cologuard has a truly ground-breaking strength in its sensitivity to sessile serrated adenomas. These adenomas have only recently been shown to be the source for 30-35% of all CRCs. FIT doesn’t detect these. In fact, recent data show that there is a huge variance between the rates at which colonoscopists detect these with detection rates for some approaching 0%. This changes how one performs simulations of the efficient frontiers and cost-effectiveness. Indeed, it is one reason I think this test is a huge improvement over FIT. Similar arguments can be made for the equal sensitivity of Cologuard, but not FIT and not colonoscopy to proximal and distal lesions.

    To say that the “perfect” sDNA test would only garner a reimbursement of around $237 (in 2007 mind you), and therefore Cologuard could never be reimbursed higher is a preposterous argument because the imperfect colonoscopies and especially sigmoidoscopies already cost significantly more than that. These are complicated arguments, and also were performed at a time when the importance of sessile serrated adenomas were not appreciated.

    I’ll stop here, but it is almost pointless arguing further since we’ll have the real answer very soon.
    Apr 30, 2014. 06:13 PM | 7 Likes Like |Link to Comment
  • Should Exact Sciences Buy VolitionRx? [View article]
    There are a large number of caveats to be noted in this article. First off, to compare the preliminary results from tiny sample sizes with a large prospective clinical trial is not really meaningful. The results reported so far are so tiny as to give almost no clue as to whether or not this method will be successful. The company itself is not running any clinical trials that are listed on clinical trials.gov, nor are any of the trials you referred to in your table findable on that web site. To obtain FDA approval for a device the trials have to be registered at clinical trials.gov. What would appear is that maybe, possibly, VolitionRx has a deal to get blood samples from other ongoing clinical trials that are not targeting VolitionRx's method as their primary or secondary endpoint otherwise they would show up on clinical-trials.gov. Therefore, it is very hard to draw any really meaningful conclusions from the numbers you present in the table.
    Your criticisms of the Deep-C trial design suggest you don't have much familiarity with design and interpretation of large clinical trial data. First off, patients with inflammatory bowel disease are excluded from almost any screening trial of CRC due to the fact that they are recommended to have, in many cases, yearly colonoscopies. Further, these patients are at higher risk for CRC. This condition is currently undergoing a separate trial by Exact Sciences (called OCEANIA; NCT01819766 - at clinical trials). Second, exclusion of other subjects with familial risk of CRC is also common in trials of CRC screening since it would act to increase the potential sensitivity of the test. Otherwise it was a randomly selected general screening population. What you criticize as flaws are actually good practice for designing such a trial. Further, as Energy Trader pointed out, 64 patients with cancer is close (a little over as ET pointed out), to what one expects from a screening population this size and the size of the screening pool was specifically designed to attain statistically significant results counter to your contention.
    There are many biological reasons not to prefer blood as a screening medium for CRC as described by Dr. Bert Vogelstein, the pioneer of CRC screening using molecular analyses. It would be great if a blood-based screen for CRC could be developed. But based upon what is out there so far for all that can be said for VolitionRx is that maybe they have something.

    Here are quotes from Dr. Holdenrieder, one of of the developer's of the nucleosome approach who is performing the small trials for VolitionRx from Dec. 12, 2013:
    "When compared with healthy controls, the sensitivity for the detection of colorectal cancer was 75% at a specificity of 70%. At 95% specificity, the detection rate was 33%. " A specificity of 70% is not useful in a clinical screening setting.

    "...will have to be further investigated in larger cohorts to see whether NuQ-5mc detects also polyps that potentially could progress to colorectal cancer."

    This is a field in the very early stages of development, and this fact is reflected in the market cap of this stock. All that can be said is it shows some promise.

    With regards to compliance with stool screening, Exact Sciences has developed a "compliance engine" approach that will be used and performed by the company to enhance compliance with the sampling. During the Deep-C clinical trial, the CEO of Exact stated that the main problem was not compliance with the stool test, but compliance with the colonoscopy. That is why they lost over 1200 subjects that were enrolled to bring the final sample size down to 10K.
    Dec 22, 2013. 09:55 PM | 1 Like Like |Link to Comment
  • Exact Sciences Has Huge Potential [View article]
    EPI has a history of being less than transparent with the performance data. For instance, until the Church paper was finally published early this year, EPI never let out just how bad the performance of the test was. Now you are believing that a test that was worthless as a screening tool has suddenly morphed, using the exact same marker, into a test that will out-perform FIT. I have a hard time believing that until I see a peer-reviewed paper with a large, prospective, screening population.

    It is also a fact that mSept-9 is elevated in a number of other cancers, not just CRC, thus in a very large screening population this would lead to a lot of pointless tests. You may look down your nose at Google scholar, however that tool lets you find that septin-9 is elevated in both head and neck cancers as well as breast cancers.

    I strongly believe in evidence-based medicine. If the m-Sept data comes out looking goof (and is published in a good peer-reviewed journal with the data from the entire screening population), who knows maybe that will be a good investment too. Based on what I've seen so far in 2013 with the only credible evidence we have, I would say it is a bad test.
    Nov 11, 2013. 05:50 PM | 2 Likes Like |Link to Comment
  • Exact Sciences Has Huge Potential [View article]
    I am referring to the PRESEPT study as the pivotal study because it IS the pivotal study with regards to septin-9. - there is no other. EPI never conducted another large scale, prospective screening trial. So claiming there is a new, much better version of the test is not credible since it has not been vetted in a large screening trial but only in a tiny trial. However there are other studies to refer to. For instance in a cost effectiveness study of septin-9 by Ladabaum et al. (Cancer Epidemiol Biomarkers Prev. 2013 Sep;22(9):1567-76. doi: 10.1158/1055-9965.EPI-... Epub 2013 Jun 24) here are the results:
    "All established screening strategies were more effective than mSEPT9. FIT was cost saving, [and] dominated mSEPT9." That study did not examine sDNA.

    Bottom line - maybe septin-9 is better than doing nothing, with that I would agree. But is is inferior to FIT since it is so much more expensive.
    Nov 8, 2013. 01:02 PM | 3 Likes Like |Link to Comment
  • Exact Sciences Has Huge Potential [View article]
    Dr. G., For someone who claims to be performing CRC research and also claims that a blood test is going to be reviewed soon by the FDA you don't seem to be up on the most recent facts. The only blood test close to FDA review is the one based on septin-9 methylation, and that test IS currently under review (not going to be reviewed as you stated). In fact, the test has now been under review for quite some time. As far as the efficacy of this test, well here are the conclusions from the PI of the FDA trial called PRESEPT in the paper that was published on the data from the PRESEPT trial (Church et al. Gut (2013) "Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer."):
    "In conclusion, the blood based mSEPT9 assay detected about half of the preclinical CRC with specificity similar to guaiac based FOBT, in this prospective masked study of screening subjects. Sensitivity of mSEPT9 for advanced adenomas was very low. Although this renders the clinical utility very low, there might be ways to achieve possible improvements, as suggested by our post hoc analysis as well as by a recent case control study.24 The utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas."

    That's right, they detect about half of the cancers and for advanced adenomas (i.e. pre-cancers) here is what they found:
    "For AA, sensitivity was 11.2%, only minimally higher than the positivity rate for subjects without any pathology (9.1%)."

    I have scoured pub med and clinical trials.gov and haven't found another newer blood based test that is close do you know of one?

    As far as the capsule goes, that technology doesn't even have a large screening trial recruiting yet. Thus, the ability to make statistically meaningful comparisons of that technology to either Exact's product, FIT or colonoscopy is years away.
    Nov 7, 2013. 03:02 PM | 4 Likes Like |Link to Comment
  • Exact Sciences - Appendix: Answering The Critics [View article]
    That 9 year chart is fascinating - 100% compliance over 9 years. This really stirs the imagination. Just imagine a test that performs at the noise level will find almost all pre-cancers with just 20 years of testing! There is no need to waste R&D dollars on finding better tests since all that is needed is programmatic compliance with even a lousy test.

    Why is anyone not just using a $4 FOBT instead of a $25 FIT? For the same cost one has to screen 6 times less often with FIT. Therefore if FOBT has a sensitivity of 14% and FIT 23% 10 gFOBT screens will find 586 pre-cancers vs. 549 for FIT in 5 years at a cost of only $40 vs. $125 for FIT. Therefore, FIT dramatically underperforms gFOBT. All kinds of cool Excel multiplications here. Should one start shorting FIT stocks next?
    Jul 31, 2013. 11:50 AM | 4 Likes Like |Link to Comment
  • Exact Sciences - Cologuard Is Strike 3, And EXAS Is Out (5 Of 5) [View article]
    Why won't you answer the question? And, yes, the implication of your profile is that you are an individual investor. Otherwise why not just state that you work for a hedge fund, and that this article was produced for them? That would be the most transparent and least confusing option.

    What about responding to the other questions? Do you really think that Exact won't produce the FIT data in the publication from the DeeP-C trial? Somehow, though you couldn't wait for the publication.
    Jul 30, 2013. 02:04 PM | Likes Like |Link to Comment
  • Exact Sciences - Cologuard Is Strike 3, And EXAS Is Out (5 Of 5) [View article]
    So, this five part series is, as reported by Adam Fuerstein in his Biotech Stock Mailbag, work performed by a Hedge Fund that is short EXAS, and yet in your profile you try to pretend that you are merely an individual investor. Why don't you come clean was this series produced as a contract, in the employ, or at the request of the hedge fund or is this simply the work of an "individual investor"?

    You can't possibly expect people to give credence to claims of deception on the part of a company when it appears the author is being far more deceptive. Fuerstein also highlighted how you have played fast and loose with the numbers from Insure FIT. Further, your claim that the Insure FIT is better than any other FIT (not the g-FOBT) is not backed up by a large comparative study. Insure FIT has NOT been evaluated in a large prospective gold standard screening study with full comparisons to colonoscopy like the DeeP-C trial. Therefore any claims you make about its superiority are not rigorous. The Morikawa study published in 2005, which you continually refer to as out-dated was a gold standard, large (greater than 20K) trial with colonoscopies performed in all subjects. Somehow, though, you view the much smaller, flawed study of Insure published in 2006 as state of the art. See again the Biotech Stock Mailbag piece to see where you inflated the performance of Insure. Come back and report to us when Insure runs a prospective screening trial of >10K average risk subjects where each subject has a colonoscopy to see how it performs.

    Your entire series would have been much better served by waiting for the full comparison between Cologuard and FIT which was submitted for publication in June and will likely appear in the fall.
    Jul 30, 2013. 01:53 PM | 7 Likes Like |Link to Comment
  • Exact Sciences - Flushing $$$ Down The Drain (2 Of 5) [View article]
    All the numbers presented here for FIT being superior are predicated upon a three year repeated screening. As a commenter pointed out yesterday, it is not even clear that one can assume that the multiplicative probability calculation for FIT is actually true since it assumes there is a random probability for any given polyp to bleed. But most damning in this analysis is the assumption of 100% adherence to repeated yearly testing. This is a total fantasy. The study that I cited yesterday showed in year three the compliance was down to 66%. Those data were smallish and came from Hong Kong and involved three follow-up letters in a year. A much larger, more realistic study in the US looked at 11,110 subjects who had already taken their fecal blood test. They found that compliance with even the second test (never mind a third) dropped to 44% (Fenton et al. Ann Fam Med. 2010 Sep-Oct;8(5):397-401). This is the unfortunate reality of screening in the real world.

    I also point out that in yesterday's article the author continuously misleads readers by comparing apples to oranges clinical trials. The ONLY FIT study with a gold-standard design similar to Cologuard's was the Morikawa trial from 2005, but the author persists in making comparisons to smaller, non-screening trials - a deliberate attempt to mislead from a guy who claims that Exact Sciences is trying to mislead people.

    The cost of FIT certainly makes it attractive, if you aren't worried about finding cancers in the proximal colon.
    Jul 25, 2013. 03:47 PM | 1 Like Like |Link to Comment
  • Sequenom: Disruptive Innovation Is Driving Investment In NIPT [View article]
    Well of course it is easy to predict with a contract in place and signed. However, the demand is clearly outstripping the total lives covered. And I am guessing a lot of sales are to women not covered under contract since this test has really spread via word of mouth (is there any group more wired into products and trends than new and expectant mothers?). This has led to a lot of confusion. My friend got the procedure with no contract in place and she said there is a lot of confusion at both the clinic and at BCBS as to what is going to happen and how much she has to pay. Having a contract will resolve these issues.
    Jun 5, 2013. 10:56 AM | 2 Likes Like |Link to Comment
  • A Game-Changing Cancer Screen For Exact Sciences [View article]
    I wanted to thank those who commented for their kind words. Gordon, the NYT times article really highlights the problems with the expense of colonoscopy. The high expense is quite a burden when used as a screening tool, so a cheaper alternative with good performance is really necessary. In fact most countries don't use colonoscopy as their first line CRC screening tool. I agree with Rick Berger, that this test is not ready, with its current performance to displace colonoscopy. The reason is that even though its performance, when considered programmatically, can get closer to colonoscopy the data available with FOBT/FIT shows that there is very poor compliance with using those tests yearly as they should be. Since the recommended interval for Cologuard will likely be 3 years this might mean better compliance than the yearly FIT, but we still have to assume that there will be imperfect compliance with the 3 year interval. Therefore, the performance of Cologuard, which is significantly better than FIT will make it such a compelling first line screen for those who simply refuse colonoscopy.
    Jun 4, 2013. 11:03 PM | 1 Like Like |Link to Comment
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