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Hayward,
Appreciate the attention to detail. I was speaking in that instance of my personal experience, hence the “I.” Other members of MRC have little to no market experience. But we all have as company policy agreed, subject to audits, not to actively trade securities while members of the company, AMRN included.
Best of luck to you.
ggwpq,
Thanks, we’ll retract the second half of our statement on management’s silence on an AdComm, but not the first half that accurately conveys the preliminary plans for an AC from FDA in the 74-day letter.
We expect an AC.
Regards,
-MRC Team
Flubber,
Our non-executive members did absolutely not want to be identified, which I (yes, I) expected. Imagine you are an academic at an institution and suddenly your employer gets dozens of phone calls complaining about something written that “implicates the institution,” with a variety of threats of lawsuits etc because they (the callers) are scared and overextended in an investment (probably options)?
Writing a factual but negative report on Amarin or any publicly traded company celebrated by a large group of retail holders (notice if we wrote a negative report on a private company few would care?) will bring this kind of backlash every time. I’ve been in the market for a while and am quite familiar with it.
Good luck to you.
Rafunrafun,
What’s funny one day can be something to cry over the next. The joy in holding a “multi-bagger” (AMRN) and the feeling of being right can quickly turn into sorrow when a black swan event materializes.
Seeking out a registered investment advisor and picking their brain for a few, on hedging techniques and risk in particular, is a good idea for anyone, but especially for one that has a disproportionate amount of their NPV in one asset.
Good luck to you also.
Tatsytheelf,
No need to disclose until date given. This is common practice.
You can see here clearly the effect we’re having on Amarin and the perception of them amongst the investment community.
sharinsky,
No, we wouldn’t make anything up. We care about accuracy and building up our reputation. Please see:
https://www.fda.gov/media/81306/download
afford567,
We’re looking at 7 other healthcare companies right now, narrowing it down. Will likely write our second report within the next several months. Probably a NASH play. We’re a small shop right now and our non-executive members are involved in MRC as an extracurricular pursuit at the moment, but that may change depending on demand. Also, we want to be sure to meet our consultation commitment to clients. Maybe in time we can ramp up to 10 or so reports a year.
Our goal is for this company to be known for the depth and quality of the analysis it produces. For example, consider buyside analysts covering Amarin. The analysis is as shallow as puddle water. It’s well known the only utility analysts bring is access to insiders for more color. What they say about this or that company is of little value to investment firms, with notable exceptions of course. What we bring to the table stands in stark contrast to their vast shotgun approach. Who really needs a shallow overview of hundreds of healthcare plays? But, that’s mostly what’s out there. So, we saw a need and an opportunity and went for it.
Good luck to you.
Rafunrafun,
You are invested in Amarin Corp., not REDUCE-IT. Amarin Corp. = Vascepa. Therefore you own Vascepa in small part. How secure are you in Vascepa, given that the FDA may not expand the label for its use, and one can purchase the API very easily, and generic companies are currently pursuing the right to sell knock-off Vascepa, and the FDA has by omission called ethyl ester EPA a dietary ingredient?
That’s the question AMRN bulls need to consider to construct a risk/reward model and allocate capital long, short, or not at all, hopefully with some assistance from a registered investment advisor who can help you and others understand the risk involved (and potential hedging techniques). It’s easy to get in over ones head in the stock market, taking completely unacceptable risks and hurting loved ones as a result. Luck is nice while it’s here, but luck always runs out.
Consider carefully. It’s not just (collectively) you and you being right/wrong here. Lives have been ruined and families torn apart due to not respecting risk, which is often just the result of honest delusion. We’ve all been overcome by belief of one kind or another and subsequently behaved irrationally. Now’s the time to reconsider your beliefs in AMRN, while the stock is trading around highs and the account is flush and before the two catalysts that could result in bankruptcy for AMRN (and apparently a number of its holders) come upon you. Because you absolutely may be wrong.
VuBru,
If a settlement occurs you all are not going to like the terms. But it’s very unlikely to occur. The issue is Vacepa = Amarin. That is all Amarin is. Amarin will only settle for a deal similar to Teva’s. And in our view Teva only settled because they knew DRL/Hikma would not, and would likely win, and thus they received millions, saved millions (and time), and only lost a handful of potential months selling Vascepa due to 180-day exclusivity. And at the time of the settlement REDUCE-IT data was unknown, and the trial deemed unlikely to succeed, and Teva already had a large stake in the TG>500 mg/dL market anyway. And Teva was (and is) facing financial difficulties.
The Teva settlement should not inspire confidence, it should unsettle you all as AMRN bulls. It was just optics for Amarin, and if anything reveals their insecurity in their own IP.
Chas123,
How about a direct quote with a link so we can validate and consider your remark factual?
Sharinsky,
Most patent litigation actions settle out of court. Are you not aware that multiple settlement conferences have occurred (as protocol) in the ongoing litigation and of course, no settlement? The odds of a settlement this deep in the discovery are not high. And what with the REDUCE-IT indication on the line, makes a potential settlement even less likely.
chas123,
We never said K/M curves were tea leaves, Charles, only this unscientific interpretation of them you are ascribing to. But, since you are focused on their shape so much, we’ll allow that there are a handful of normalities associated with these curves we could discuss. For example, very large trials will have a much more steady-looking curve than those from smaller studies. This is because the event rate does not fluctuate nearly as much. And there won’t be much of a “tail,” as is often seen with smaller studies, and in particular from immunotherapy trials. But, these are all very general observations and do not at all allow one to make sweeping statements about a given arm of a trial, as you are attempting to. You even go so far as to say:
PSea,
You only now became aware of the claims construction?
Bearish AMRN Report (part 3): by Medical Research Collaborative, LLC (sample pages)
https://medicalresearchcollaborative.com/reports?product_id=51
2. The Assailability of Amarin Corp.’s Patent Portfolio
2.1 Obviousness and Prior Art
Title 35 (pre-AIA) of the U.S. Code lists the following as conditions for patentability, giving at the same time a working definition of “prior art” relevant to all patent applications filed before March 16, 2013 (or pre-Sept. 16, 2012 for § 112):
rafunrafun,
That isn’t a bad idea, and was considered. We did in effect say just that in our “About Us” section. Regarding our overview on Amarin, and sample pages reflecting expert-level content, we have already received multiple confirmations that members of the healthcare and investment communities view the content to be just that, and the interest in our report on AMRN has been high. That isn’t for no reason.
Consider a fund that has $50 mil invested in AMRN. What % of that is $32,000? It’s 0.06%. Would it bother you to spend 0.06% of a position on an extensive report about that position?
JJPow,
No one has yet come remotely close to refuting anything we have written on Amarin. Not once.
Psea,
It is in fact common policy not to reveal authors in market research, for a number of reasons. That is our policy as well. Our writings on Amarin, even our simple overview and sample pages, clearly reflect a high level of expertise in the subject matter. We think that content should stand or fall based on its own merits.
Charles,
As we in effect said on Twitter, and found no reason to continue the dialogue thereafter, a “tea leaves” reading of the REDUCE-IT K/M curves is incoherent, and “hokey”. Shouldn’t it be immediately obvious why such an unscientific “reading” of the curves has no basis in reality? The most obvious refutation of your claim is that any harm done to placebo group subjects would of course begin from time zero on the curve. Immediately, their risk changes upon entering the study and consuming mineral oil concurrently with cardiac medications. Their risk rate is higher and constant from then on.
You might have an interesting observation if they were already followed for years and then began taking MO in the study, and then we could view a curve that was -5 to 0 to +5 years, but of course we don’t have those data (not to mention we cannot see any of the censors on this plot, but that is another story).
tm100,
Did you know that another company sought to use mineral oil placebo sometime after FDA had reviewed ANCHOR data and the FDA advised against it?
Tastytheelf,
Also, you are factually incorrect that the mean LDL-C change from baseline in EVOLVE’s olive oil placebo group was “+11.7%”. It was in fact an insignificant +3% mean change.
Tastytheelf,
In EVOLVE, which had a similar lead-in stabilization period as ANCHOR, there was noted a 10% increase in median LDL-C in the olive oil placebo group. However, other atherogenic markers were reduced or did not significantly change in this group. Also, the least squares mean value recorded in the study (which reflects changes across the entire arm) showed an insignificant 3% increase in LDL-C in the placebo group. It seems then that the elevations in LDL-C primarily occurred in those placebo group subjects with baseline values near the median, and little change in the rest.
There could also have been some impact on LDL-C from the modest TG and VLDL-C lowering effect of olive oil (-10% and -11% median change, respectively) by mechanisms similar to those by which DHA can cause an increase in LDL-C along with a decrease in TG and VLDL-C—especially in those with very high triglycerides at baseline. An increase in LDL-C from a triglyceride-lowering therapy is much more likely to occur when the baseline TG levels of subjects are very high. In ANCHOR, the median baseline TG level was ~260 mg/dL, and in EVOLVE it was >700 mg/dL, and so an increase in LDL-C from a TG-lowering therapy would be more likely to occur in EVOLVE than in ANCHOR. The discrepancy in changes in median and mean TG values (-10% vs -4.3%, respectively) from baseline in the olive oil placebo group in EVOLVE also lends credence to the possibility that such a phenomenon affected those with values near the median more than the rest of the group. Thus, the comparison between EVOLVE and the ANCHOR/REDUCE-IT trials breaks down on multiple levels.
Importantly, most of the atherogenic/inflammatory markers in EVOLVE’s placebo group either decreased (such as TG and VLDL-C) or stayed the same. LDL-C was the exception. By contrast, the highly significant increase of all eleven atherogenic/inflammatory markers tested in ANCHOR, and confirmed in a separate study with patients of equivalent background therapy and characteristics (REDUCE-IT), is much more reminiscent of a treatment effect than a regression to the mean.
sharinsky,
You will have to read our report to see. We present evidence that mineral oil (and other synthetic lipids) can cleave to partially dissolved compounds and thereafter they are both eliminated from the body with very little being absorbed. There is no need for the intestine to be “coated” or anything like that.
rafunrafun,
What you are not considering is all the harm that would come to patients and payers—and so all of us—should an ineffective therapy be approved and thought highly efficacious. Patients and healthcare professionals will opt for Vascepa over a therapy that could truly help them, being blinded by the stated 25% RRR. They may even pull back a bit on taking other medications such as statins, presuming Vascepa is doing the job enough. Lots of issues. It would be pernicious.
ggwpq,
Regarding the JELIS trial, there are major limitations to the study that make generalizability difficult. It was open-label, and open-label trials are notorious for reporting exaggerated treatment effects; and the only significant individual finding from the trial was a reduction in unstable angina, with well over half of the primary endpoint events comprised of these (193 vs 147 events, p=0.014). Therefore, there is an increased likelihood the results were due to performance bias and/or detection bias, resulting from changes in patients’ behavior, physicians’ treatment, or event ascertainment. It was also comprised of a 100% Japanese population of patients with poorly controlled LDL-C (182 mg/dL at baseline); nearly 70% were women; all were given very low dose statin regimens, even for an all-Asian population (pravastatin 10 mg/day or simvastatin 5 mg/day), and around 27% of the subjects discontinued statin use during the study (whether or not more control group subjects discontinued statin use earlier than ethyl ester EPA (EPA-E) group subjects was not disclosed).
Importantly, in JELIS, the MCE composite endpoint itself was different from that in REDUCE-IT. It included revascularization and hospitalization for unstable angina, but did not include strokes. In order to make an apt comparison with the REDUCE-IT trial—ignoring for a moment the numerous differences in populations and background therapies—the same composite endpoint should be used. When this is done, with strokes included, the RRR in JELIS decreases sharply from 19% to just 11.5%, insignificant from 914 events ([324 vs 262 non-stroke MCE; HR 0.81] + [162 vs 166 stroke events; HR 1.02] = blended HR 0.885). Comparing the reported 19% RRR in JELIS with the 25% RRR in REDUCE-IT is therefore misleading.
Not only this, but there was no perceived effect on coronary death (HR 0.94, p=0.81) in JELIS, and all-cause mortality trended worse for treatment group (265 vs 286 events, HR 1.09, p=0.33).
It can only be said that in this open-label, 100% Japanese, 70% female-gender study, 1.8 g/d EPA-E (aka “IPE”) significantly reduced unstable angina in subjects not optimally treated, with the potential for bias to have overinflated the result. JELIS is not a trial that reliably shows IPE can significantly reduce the risk of ASCVD events, particularly not in a patient population similar to that of REDUCE-IT.
Furthermore, a positive result from one study is often not reproduced in later trials. This is one reason that FDA normally requires at least two adequate and well-controlled studies as proof of efficacy and tolerability.
For example, the GISSI-Prevenzione trial, which tested 1 g/d omega-3 ethyl esters (OM3-E) vs control in over 11,000 Italian post-MI subjects, demonstrated a significant 15% RRR in the primary MCE composite, which included all-cause mortality, MI and stroke. The study showed a 20% reduction in death from any cause and a 30% reduction in CV mortality (each also significant) compared with control. There was also a 44% reduction in sudden death (p<0.01). This led to Omacor 1 g/d (aka “Lovaza”) being indicated for secondary prevention (following MI) in major EU member states. The AHA also began recommending 1 g/d omega-3s for secondary prevention, though there was no formal FDA approval for that indication. However, subsequent placebo-controlled trials did not reproduce the positive findings, and as contrary evidence continued to mount, the EMEA eventually decided to retract their approval.
What happened here? Was the result due to the open-label design? It does not seem possible that that could have affected an endpoint like mortality. Was it due to differences in background therapy between GISSI-P and more modern trials? That could be a plausible explanation, as most of the subjects, especially early on in the study (when much of the benefit in mortality was realized), were not on statin therapy. It is possible that the reduction in sudden death in particular was the result of antiarrhythmic and antifibrillatory properties that have been ascribed to omega-3s. These same properties are also ascribed to statins, particularly at higher doses. There were likely untreated targets present due to lack of statin therapy in GISSI-P subjects. Later trials were conducted in an era where all secondary prevention subjects are given moderate to high-intensity statins following an MI (as well as numerous other treatments and cardiac medications). JELIS enrolled all of its subjects between 1996 and 1999, similar to the GISSI-P trial (1993 – 1997). Would the open-label JELIS trial results involving 1.8 g/d of EPA-E repeat in a placebo-controlled test with optimally treated modern-day subjects of Japanese descent randomized over 20 years after the fact? Perhaps not.
Generalizability of study results is crucial in informing drug regulation. 1 g/d OM3-E offers no additional benefit to secondary or primary prevention patients already on extensive background therapy, even though it proved effective in the GISSI-P trial. The JELIS trial subjects and REDUCE-IT trial subjects are too different and were too differently treated to confer anything from the results of one trial to that of the other.
rosemountbomber,
Why do you think a company must divulge confidential discussions between the FDA and its board members? Of course they don't. It limits what they may say/do thereafter, and for that reason they may divulge it, but they do not have to. Only if someone that is not an insider and has not signed an NDA and may trade on the info had gotten hold of the info must it then be reported promptly. The urgency must match the level of leak. If precedent is to be your guide, many times the AdComm is not reported until they are given a set date for it, and that often happens a month after a priority review announcement. So about 90 days from submission.
rafunrafun,
There is a responsibility in posting on a public forum under a company handle, and it de facto requires you are speaking on behalf of the company, hence the "we". Some of these posts are vetted, some not. If depends on the content. Speaking on points contained in our report doesn't require internal compliance checking so long as certain topics aren't mentioned.
In essence, right now this is a form of advertising.
The exceptionally small p-value is expected if the groups are imbalanced and the study confounded. So, it hurts as much as helps.
dukesking,
These are exaggerations, especially on purity. In fact we found some interesting ties behind the studies testing off the shelf omega-3 supplements, and much evidence their methods were poor, which we elaborate on in our 226-page report. In actuality, certain concentrated omega-3, including EPA-only supplements, pass more stringent standards (GOED) than the USP-NF.
But to help you a little, here you can see just how pure many of todays EPA/DHA supplements are:
https://www.nordicnaturals.com/en/Retailers/Third-Party_Test_Results/860
You may also look up these COAs here:
https://www.nordicnaturals.com/cofa/
Whether or not DHA is good or bad is something you do not know. There are obvious and well-documented benefits to DHA consumption (decrease heart rate and blood pressure, as well as anti-oxidant properties), and there is one potential detraction in increased LDL-C, but this is limited to those with very high triglycerides at baseline (> 500 mg/dL), which is a vast minority. And there is much evidence eating more fish = less risk of ASCVD, and all fish have DHA, with many genus having more DHA than EPA. So, I wouldn't be too rash in dismissing DHA, or worse, labeling it "bad".
Also, you may not be aware, but it all comes to API regarding bioequivalence and what FDA considers effective. 505(b)(2) approvals do not require outcomes studies of their own, they simply must prove an equivalent API and potency as their reference listed drug counterparts. Although these off the shelf supplements are not considered generics (and will not be considered them, unless EPA-E becomes switch-OTC someday, and it might), they in essence are. Thus, they need no outcomes studies to be used. And with so much third party testing data out there, docs can rely on that to advise their patients to use them in place of Vascepa. We even found a medical institution that carries and recommends them (they actually say "prescribe") in its in-house pharmacy.
"boozeman",
We think the ADA recommendation was prudent given the safety profile of ethyl ester EPA (something you can get OTC), and given the apparent efficacy. But, it does not prove anything, and does not portend the direction FDA will go, who will have access to the entire data, and will scrutinize all aspects of the study, including any evidence suggesting the malabsorption of cardiac medications in the placebo group. Such a pleasure the ADA does not have.
There was a time when the AHA recommended 1 g/d omega-3s for secondary prevention patients. That went away as new evidence came to light.
Biobillionaire,
Again, they are all fatty acids. As far as the Amarin v. AZN action, it had no merit, but neither did it merit the loss of capital and time defending. AZN will easily win whatever action comes their way regarding IP over Epanova in the future. We cover this extensively in our report.
Amarin, however, will not be so lucky, and we are confident they will lose in January.