The 13 before DU decision reflected uncertainty about Du's decision or if you look at the progressive selling before decision a possible leak. Amarin's worth, in light of recent studies/evaporate/etc., is at least > 26 if we win patent in the short term. 31 is reasonable. I do not believe her 2 dollars is reasonable if we lose the case. ROW + europe + cash in hand should be worth at the very least 8+.

The 13 before DU decision reflected uncertainty about Du's decision or if you look at the progressive selling before decision a possible leak. Amarin's worth, in light of recent studies/evaporate/etc., is at least > 26 if we win patent in the short term. 31 is reasonable. I do not believe her 2 dollars is reasonable if we lose the case. ROW + europe should be worth at the very least 10+.

Not a lawyer, but I am a doctor and I have read a lot of research papers. In NO WAY does the MORI trial with such a small subject population, with specific BMI OF 25-30 (lipids act differently at different bmi - central obesity), TG < 500, and ONLY MEN would pass as a valid study to make ANYTHING obvious about a general population of men/women w/ TG>500 .

Reviewed and agree with your analysis. Her other flaw was that she selectively allowed studies that did not have the same inclusion criteria as MARINE and had a very different subject population statistics to invalidate MARINE's non obviousness (importantly triglycerides >500, all males, only overweight but not obese). Interestingly, she used a set of criteria to bar REDUCE IT data from being relevant to the MARINE indication. This set of criteria significantly focused on inclusion criteria of MARINE / REDUCE IT. IF she had used the same logic of comparing inclusion criteria the generics' studies should have ALSO been barred. To quote an analysis of her judgement on why REDUCE IT cannot be included:

"For five separate reasons, Judge Du found that the results of REDUCE-IT lack a nexus to the asserted patents in this case. According to the Judge Du’s opinion: (1) REDUCE-IT involved use of a statin, whereas the asserted patents do not require use of a statin; (2) REDUCE-IT was not directed to reducing TG levels, as required by the patents; (3) REDUCE-IT was not directed to not reducing LDL-C, which is required by most of the patents; (4) REDUCE-IT was directed to patients with certain cardiovascular risk factors, which are not required by the patents; (5) REDUCE-IT was directed to patients with TG levels below 500, whereas the patents are directed to patients above 500. Based on these five reasons, Judge Du held that REDUCE-IT was irrelevant to the patents actually asserted in this case."

At least 3 of her five stated reasons that REDUCE IT does not apply had to do with difference in inclusion criteria (patients on statin, with cardiovascular risk, and TG less than 500). There were huge differences in inclusion criteria in the MORI and other studies than the MARINE trial. Most pertinent been mentioned above of all males, fixed bmi between 25-30, and TG all <500.

I am not sure what AMARIN gains w/ expedited appeal and that may be why they would not pursue it.

1. It should in theory not change appeal outcome.
2. As long as appeal is in place generics are too scared to enter "at risk launch" given their potential penalties is from a brand cost perspective while they would only profit with generic margin from what they sell. This buys amarin 1-1.5 years to continue selling their product.
3. Even if they win the appeal decision sooner if expedited, now is not a good time to sell the company with the current COVID epidemic.

All these articles you are citing all stem from the Wainwright's comments. Look at this site:

https://www.plainsite.org/judges/nevada-district-court/miranda-m-du/

She had 1 case in 2019 and 3 cases in 2018. None were patent. Saw a few patent cases in 2017, but they were not an issue of generic trying to enter a market as far as I can tell.

Listen to the phone call. The patent lawyer's record is very impressive. Teaches at Harvard among other things. He was very clear that she had a great history as a bench judge, but this was her FIRST PATENT case as a bench judge.

This conference call was very reassuring about how Judge Du royally screwed up.

This is kinda crazy and I have literally already lost a nice house on this already, but this feels like a buy at this level.

1. 650 million cash in hand + possible value of tax loss carry forward (was it like 600-800 mills?)
2. The review from markman advisors basically illustrated it will make no sense for generic to try to launch before appeal win. It took TEVA 6 months from appeal win to launch. Appeal verdict will take at least 1 year from now, so effectively the earliest generic entry will be 1.5 years from now, but realistically 2 years. If AMARIN just scales down advertisement right now and cuts US sales staff w/ a profit margin of 70 percent and on track for 1 billion this year they could be up in 1.5 to 2 billion in cash in 2 years. That's already 4.5 dollars in value in the share price.
3. Some probability of success on appeal. Though probably small. Let's say 10-20 percent.
4. The rights to the European market and rest of the world should be at least a few billions.

Overall it looks like we already had the worse risk take place and value of company is at least 8-9 dollars. Sounds like a buy. Am I missing anything ?

Good review of the loss and potential future challenge by AMARIN.

https://www.markmanadvisors.com/blog/2020/3/31/can-amarin-win-on-appeal-in-the-vascepa-patent-litigation

The bond should only cover potential profit loss from MARINE indication right ? So it would be negligible.

That looks like the right article. I understand I may be bias, but as a physician who reads a lot of different clinical studies this does NOT constitute enough evidence for obviousness. It is small (n=50s), ONLY included MEN, did NOT exclusively target >500 Trig (marine label), and patients had a fixed BMI between 25-30. It also had no mention of EPA lowering LDL (one of Vascepa's patents under contention I believe). My interpretation of "obviousness" is can a company submit this study to the FDA and expect them to give approval for that indication and will doctors read the study and feel keen to prescribe the drug for that indication. The answer is a resounding NO on both accounts. There are many studies of other drugs w/ small trials and with the number of patients in 50s that would at most raise an eyebrow and prompt additional larger studies. The reason is results from singular, small, and very focused studies are often contradicted by other small, focused studies. This literally happens all the time. I think in appeal this can easily be shown and demonstrated.

The seeking alpha article did bring up a really good point. The REDUCE IT label approval by the FDA gave us new clinical investigation 3 years exclusivity, which would limit new ANDA approval. What is less clear is that can the ANDA be approved for MARINE label if it will obviously induce infringement for the REDUCE IT label ? Can anyone answer this ?

Cherry showed regression w/ just EPA/statin I believe. There's a good chance when the full longer duration evaporate data comes out this will be reaffirmed.

Difficult to say. But titrating up your statin as tolerated is a good idea.

It is not about working around the label. I can't imagine any doctors who are decent not prescribing statin on purpose when a patient needs it just so they can work towards prescribing Vascepa. But there is a sizable population of patients who either psychologically (more so) or biologically cannot tolerate statin and that label makes it easy to keep adding Vascepa if indicated. As the label states "maximally tolerated statin". I see that and it means to me I should go to statin first and attempt to titrate up as high as I can. Vascepa is available regardless of what dose the statin goes up to. Even if the statin dose is 0. It is not that the patient has to BE on a statin before Vascepa, but the patient should have been TRIALED on statins. I can guarantee you all of the cardiovascular patients I come across in the hospital are on statin or have had multiple attempts at statin trial.

I almost don't want to respond, because I doubt it will change your view and for some weird reason you are fixed on this one intrepretation of the label. But take it from "Cardiologymd", bfost, and myself (also a physician) that the label makes it easy from a medical standpoint to prescribe Vascepa without statin. The key phrase is "maximally tolerated". If it is not tolerated then maximally tolerated is 0. What the label is really saying is go to statin and try for highest tolerated dose then go to Vascepa. Very broad label. As I am sure you know the reason the study was conducted w/ statin as baseline is because the benefits from statins are very clear and it would be unethical not to prescribe statin. This combined with the relatively small number of people with true statin intolerance makes it near impossible to conduct a study that evaluates vascepa without statin.

Okay everyone. We need to sell so Steven can cover on Monday.

I have to thank Oppenheimer. Didn't think I get a chance to add again at these prices, but now I do :). Bought more at 20.50.

This second trial just confirmed an earlier smaller trial. Practice in academic centers are already moving away from catherization. In private/rural areas catherization probably more prevalent. This study will further advance the shift from catherization. Overall favorable towards Vascepa :)

Always agreed that he is intelligent. My interpretation of his motivation is different. He misjudged the reduce it outcome. Had short equity. Realized it was too late to go long given limited gain in short term and that he can create a niche as a "biotech analyst" based on his bear thesis on Amarin. So he is just a calculating capitalist.

Counted 5-6 votes on yes to primary. One of them was tough to interpret their answer.

Funny enough Konstam comes out in support of primary + secondary prevention. He appears to just be skeptical and like to challenge all sides. At the end he follows the logic and his logic tells him primary + secondary. Definitely not fixed. The primary appears a coin flip still.

Funny enough Konstam comes out in support of primary + secondary prevention. He appears to just be skeptical and like to challenge all sides. At the end he follows the logic and his logic tells him primary + secondary.

I don't think primary label is completely out. A strong case was made at the end by two physicians.

The biggest detractor Dr. Konstam said he thinks mineral oil can be dismissed and he supports final data! Done deal.

Budoff coming through! Plaque progression in mineral oil (from evaporate) vs. cellulose (from another study) placebos are the exact same. Points to just natural change in body withtime + sick patients. Also the way he was talking - EVAPORATE IS A SLAM DUNK and will have the data of the mineral oil placebo vs. cellulose placebo plaque progression presented.

Konstam is obviously slanted. We need amarin to focus on the fact that the changes on the placebo arm is being attributed to placebo effects when it likely is simply time with a sick population + regression to the mean. They need to pull out all the PCSK9 data. They are letting Konstam / FDA statistical team define the analysis/causation.

I think it would be fair if FDA force a DDI on Vascepa it should force a DDI on all the related studies placebos.

Higher risk for rhabdomyolysis.

Re mineral oil
Just summarizing the scientific refutations of the mineral oil hypothesis.
1. Regression to mean. If your inclusion criteria for your study is very abnormal (low) for that population of patients (high cad risk w higher lipid/inflammation) then over time there is significant chance your patients with abnormally low initial numbers will show more normal numbers. Example in point is that you cannot take a track athlete's fastest time on a course as his expected future time. He will very likely run slower. This was also seen in pcsk9 studies given similar patient population /inclusion criteria.
2. Ldl differences in change from start to end of study was not linked w different cardiovascular risks in the placebo patients by post hoc analysis of reduce it data. If you say statin was depressed by mineral oil and this led to worse lipid profiles/decreased statin effect in some placebo patients, then you would expect these patients to have worse outcome than other placebo patients without worsening ldl. This was not seen.
3. If placebo nullified statin, then we would see more statin related side effects in the vascepa arm than the placebo arm. Which was not seen.
4. Assuming it is true that mineral oil affected statins' effects. Then the rise in ldl /reduced statin effect can only explain 2-3 percent rrr. There is a known calculable relationship per bhat.
5. There are many japanese studies showing epa is beneficial (jelis/cherry). Including many that definitively showed improved plaque reductiom beyond statin with epa (cherry). No mineral oil were in those studies.
6. The amount of mineral oil is neglible in context of surface area of intestinal tract and is much lower than normal dose used for constipation.
7. The adverse event rate in the placebo group was actually within expected range (slightly less than expected) for that patient population. They did this estimation prior to study start in order to determine how to adequately power their study. This is in line w inert placebo.

Any other scientific refutations? Let's avoid SPA talks. They apparently don't mean anything to the fda.

I also agree that the ADCOM is more likely 2/2 to the expected wide label. I said this in a previous post. But the post I responded to was asking what was the purpose of the FOIA and the FOIA is in no way related to wide label. It isn't just Pyrh, but all detractors. This is just Amarin covering their bases, which I think is a pretty smart. I called the offering too. Suspected it was hedge.

RE FOIA requests.


I understand some of you guys believe the requests are aimed at discovering collusion/conspiracy. Honestly, it will be unlikely for us to find anything of that sort, because it probably doesn't exist. Even if it did exist, I don't think in the event there is collusion (w/ implied illegal benefit to FDA members in some form or other) the parties involved would communicate it blatantly via official channels. So even if there is real collusion it will likely not be discoverable.

With that said I think the FOIA serves a different and still very important purpose. It is simply a brilliant move by Amarin. Specifically, to understand the playbook/agenda of the FDA ahead of time. Officially, the FDA will only release the agendas of the ADCOM 48 hours prior to the meeting. The FOIA will be able to directly pin down exactly what discussions were had between those parties. If you had analyze Pyr's posts, which I have when I started researching AMARIN in 2018, it would become apparent that he subtly manipulates/distorts truth and cherry picks different aspects of studies to serve his agenda, while purposely dismissing other aspects that run counter to his argument. If AMARIN is able to get a hold of how the detractors were able to distort the interpretation of the REDUCE IT data and specifically what angle/form of attacks they were using, then they would literally have months in advance to build scientifically sound counters to it. Then rehearse that with their representative who will present at adcom.

It is like going to into a match and you already know your opponents' playbook. With the science/truth on their side Amarin will easily dismantle it.

With that said we should compile a scientific refutation of the mineral oil hypothesis.

I sent the following email to Amarin about potential questions for tonight's conference call:

"

1. Would the results of the EVAPORATE study be available in time for the adcom? Can it be introduced during the ADCOM ?
2. Would Amarin be able to bring up the Japanese JELIS and CHERRY studies during the adcom?
3. I am sure Amarin has thought of this, but besides defending the integrity of the REDUCE IT study, would Amarin also be pushing for a wider label ? Hopefully, a label that doesn't necessitate statin (understanding that it does not replace statin) and without triglyceride cut offs given the sub group analysis showed no difference in benefit based on starting triglyceride levels. "

Any additional questions do you think will be relevant ?

Can someone contact Amarin and ask them to correct the spelling of Nissen's name in the FOIA? The other members are negligible, but Nissen has some degree of clout.

I don't think pyrrh needs to be right. His modus operandus at this point probably stems from thinking that he stands to gain more from being contrarian /going against the mass by subtle and not so subtle misinformation. Given amarin future track has such high chance of being very positive he stands to gain significantly from a reputation and then directly/indirectly monetary standpoint if he derails it. Guy has no moral compass.

They aren't looking at mace. Their "base case" is only at mi + cva + maybe chd death with modeled post first events cost. That said they allowed "first events" to stack in the same person in their modelling. It appears they may not be looking at the reduce it events total but based on their own population statistics based on the inclusion parameters of the study. It appears they will apply the hr to this population. This was one of the things amarin tried to get them to change. As an aside they made a very interesting comment. The event rate of afib /bleed was low for both vascepa /placebo. Long story short i have a theory that mineral oil is actually a cardiovascular helpful control and if vascepa was compared to air the rrr would be even better. Won't go into details. I think pyrrh is lurking and will twist it around.

Good summary.

On page 9 of the ICER model outline, right beneath the observation that there is an 18.7 percent discontinuation rate prior to first event in the initial 2 year period for Vascepa arm during the study, they wrote " The observed trial-based hazard ratios will be assigned for all patients in the first two or five years of the model(no matter the discontinuation status, i.e.,consistent with intention to treat analysis)for rivaroxaban and icosapent ethyl, respectively:" Would interpret this to mean that they would not count the discontinuation rate prior to first event against Vascepa since this is "intent to treat analysis". This was also stated last row on page 4's table. Their real rate of discontinuation / drop off will only occur after 5 years (same paragraph) and will be assigned an annual rate of 2.2 percent consistent w/ "serious adverse event related discontinuation". This is a generous approach to analysis.

With that said I read through the ICER modeling for Vascepa:

They will analyse vascepa via a "base case" route and then a separate "scenario" route. Base route to include: MI + CVA + MAYBE (CVD / total death) as first events. CV death is a maybe because their diagram did not include this third variable as first events, but parts of their written description did as first events. After first events they will include costs associated afterwards from these events. Their "scenario" analysis will include "base case" + unstable angina + revascularization.

I then compared to the Odyssey study (alirocumab PCSK9) and ICER analysis for Alirocumab to try to get a sense of likely outcome of this ICER eval of Vascepa.

For Alirocumab ICER analysis first events are: Major CHD (HR of 0.8) + fatal/nonfatal cva (HR 0.73) as first events. Their cardiovascular death was not statistically significant.
For Vascepa ICER analysis our first events are: non fatal MI (0.7) + CVA (0.71) + Maybe cardiovascular death (0.8). As you can tell we will have a clear win w/ our HR of MI / CVA better than Alirocumab Major CHD + CVA. If cardiovascular death is included as first event we will have an even more resounding win.

The analysis will also include the cost of the Serious Adverse Effects.
Afib – 3.1 (vascepa) to 2.1 percent (placebo)
Bleeding – 2.7 (vascepa) to 2.1 (placebo) percent not statistically significant. We lose in this regard to alirocumab, but the good news is that the event rate is small so the additional cost will likely have limited impact in final cost analysis.

Alirocumab costs around 5850 annually per ICER analysis. ICER is assigning us a cost of 1600. The ICER analysis concluded that Alirocumab may be cost effective at 2300 - 3500. We will likely be at Alirocumab level or even higher given our first event HR significantly better than Alirocumab w/ likely negligible small event rates for adverse afib/bleed. We will likely be cost effective. We will certainly be cost effective in "scenario" analysis given addition of unstable angina / cardiac catherization (which both have low HR).

I don't think the offer is for a lukewarm reason like anticipating expanded commercial activities/marketing. That doesn't make sense to me. They were net positive in funds this past quarter despite increase sales force/ ongoing ad campaign. The reason for the offering, especially prior to fda approval is either for a really positive or a really negative reason.

Possibilities:
1. They need hundreds of mills to settle generic lawsuits. This makes sense since it will be cheaper to settle before fda approval hence offering now. I put this under very positive. Guaranteed control of market for 10 years /time to expand position.
2. They are expecting a bad outcome with fda or generics lawsuit. Or they are hedging in case of one in order to ensure long term maneuverability w cash in had. Hedging for the risk is a reasonable possibility.
3. They want the money in hand to better negotiate with bp. Lower probability. Could better get the money post fda approval.
4. They want the money to obtain greater supply in anticipation of increase demand. Lower probability. Don't understand why not wait 2 months max. They already have guaranteed capacity for 1 billion for this year.
5. They want to start a new study related to vascepa (statin/vascepa combo?). Or obtain a different company/med w synergistic effect or synergistic sales (pivastatin?) with vascepa. Reasonable.