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Did he answer your question :)
You can't get good researchers to say something more than the data and science allow them to say. This study doesn't have the power to differentiate the progression reversal vs. regression. Hence we won't have a definitive answer on this.
But the results will incentivize and guide the company to design and conduct a bigger study to address this question more definitively. Just have to wait.
I bet that Singer's contract is very sweet even if the case is affirmed (it'll be much sweeter if it's remanded or reversed).
Really hope that Amarin doesn't pay Singer just to do a more thorough research. Otherwise some folks on this board can do a much better job at a more reasonable rate. Singer is paid for his legal experience, strategic thinking, coming up with a winning approach on convincing the court to give Amarin a different ruling, and finding a way to change the course of Amarin's commercial path in the US. His intelligence and articulation should be what Amarin is paying for. It seems that he is top notch for those.
My money is on Singer, period. That said the result is nothing but a coin toss.
sts - how they want to report the results is a decision between Amarin and IRB or FDA. I have neither problem nor opinion on it. I only stated that fact in my posts btw. However how the data are interpreted is something that anyone with a relevant scientific knowledge can objectively opine on. Isn't this the center of all the discussions of Mori or Kura on this board since March 30?
How can this statement in its PR be correct?
VASCEPA® (icosapent ethyl) demonstrated significant, 17% regression of low attenuation plaque (LAP) volume on multidetector computed tomography (MDCT) compared with placebo over 18 months.
Chem - based on the changes from the baseline, I believe it's okay to claim both regression (within V's arm) and progression halt (btw arms).
The whole confusion started with the fact that they didn't report the primary endpoint as a percentage. There may be a good reason for it. They somehow reported the % changes within each arm even though it's not part of either primary or secondary endpoints. Readers tend to gravitate to a single number better than a set of values. Hence the 17% misinterpretation.
Regardless it's neither correct nor professional for Amarin to make such a mistake in the PR. These kinda of stuff typically need to be reviewed and approved by regulatory affairs before hitting the wire. It seems that they really rushed it, probably because they wanted to disclose this before its appeal hearing or to meet the conference's timeline. Or it can be as simple as the PR person wanted to get it out quickly so that he or she can go back to enjoy the weekend.
Their first statement in the PR is erroneous (below). I think you contacted them. So they should correct it.
"VASCEPA® (icosapent ethyl) demonstrated significant, 17% regression of low attenuation plaque (LAP) volume on multidetector computed tomography (MDCT) compared with placebo over 18 months. "
Their second statement is nothing but confusing because they used a semicolon (;) instead of a period (.). The two sentences are independent statements and both are correct, but semicolon makes readers feel the second sentence is an elaboration of the first.
"The final results showed a significant reduction in the primary endpoint; icosapent ethyl reduced LAP plaque volume by 17% from baseline to the 18-month scan, whereas there was a progression of LAP plaque volume in the placebo group."
Amarin PR needs to word it more clearly.
Principal Findings:
The primary outcome, change in low attenuation plaque volume, for icosapent ethyl vs. placebo, was -0.3 vs. 0.9 mm3 (p = 0.006).
Secondary outcomes for icosapent ethyl vs. placebo:
Change in total plaque volume: -9% vs. 11% (p = 0.002)
Change in total noncalcified plaque: -19% vs. 9% (p = 0.0005)
Change in fibrofatty plaque: -34% vs. 32% (p = 0.0002)
Change in triglycerides: -89.3 vs. -92.1 mg/dl (p = 0.91)
https://www.acc.org/latest-in-cardiology/clinical-trials/2019/11/15/17/46/evaporate
Slim - thank you for the story. I appreciate it very much.
Sts - that's a good question. Epeleuton could act better than EPA through the same mechanism as EPA. Or it could achieve this through a better absorption profile. I haven't read the studies in details. If the authors didn't claim the absorption, then it's probably not the case.
Please indulge me on dwelling more on the mechanism of action (MoA) of EPA, which is largely a mystery so far. If I put my rusty researcher hat on, I imagine that there are two possible ways for EPA to function - 1) target a specific protein (typically enzyme) to change the protein's function (make it more active or less active), similarly to what statins do to HMGCoA Reductase; 2) being an alternative lipid substrate in the mix to modulate the overall lipid metabolism and hence shift a person's lipid profile to a more healthy one, similar to that if you put enough sugar, you can change any savory dish to a sweet one. In other word, a more passive role than that of enzymatic modifier.
I was on "autopilot" in my previous post suggesting the first possibility as that's most drugs do. However, thinking it more, I'm now leaning towards 2) because of the adjunct status of Vascepa (and Epadel).
Regardless, 15-hydroxy group changes the 3D structure of EPA quite a bit. It could make Epeleuton a better substrate than EPA for the metabolic pathway that EPA is involved, and hence more efficient in modulating the lipid profile shift.
The biggest difference between the two MoA possibilities is whether we can get off the fish/algae supply chain. If it's 1), researchers may be able to design a synthetic molecule (hopefully with simpler structure) to achieve the same or better result. Once it's done, we will no longer need the current EPA supply chain. If it's 2), then we will be hooked on fish oil forever. If that's the case, I believe the value of the EPA ecosystem actually resides in the pure EPA supply, not Amarin. Now you know how flabbergasted I am by Amarin's determination to GIA.
Duke - in the Epeleuton patent link someone just posted here, the inventors disclosed how they produced the molecule. They used EPA and it only takes one reaction.
http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=10,570,083.PN.&OS=PN/10,570,083&RS=PN/10,570,083
In Step 1, EPA (1) is converted to its corresponding 15(S)-hydroxy compound (Compound 2) (15-(S)-HEPE) using reagents oxygen, borax, L-cysteine and specific enzyme LPX1 of appropriate concentration. In Step 2, the 15-(S)-HEPE (Compound 2) obtained from Step 1 undergoes oxidation with MnO.sub.2 in dichloromethane (DCM) to obtain 15-oxo-EPA.
Duke - I've not looked into how it's made, but I don't remember hearing it when I was in the O3 business. So I believe Epeleuton is produced through chemically modifying EPA, mostly like ethyl EPA, not free carboxyl EPA or O3. So yes, Epeleuton is a "first cousin" of EPA, from fish or algae (plant).
It's well known that lipid molecules are notoriously difficult to handle and modify as they're not water soluble. One has to use very nasty solvent to dissolve them so that they can be used in reactions. If you show the chemical structure of EPA or Epeleuton to any chemist or biochemist, they will tell you that it's not possible to synthesize this structure from "scratch" in a test tube.
If I were Afimmune, I would only run a minimal size trial in US to show the MACE rate, which may only cost 1/2 of that of RIT.
I am behind the posts on the Epeleuton topic. Never heard it before. But I took a quick look at the molecule and company. It's a derivative of EPA, but the 15-hydroxy addition does change the tail end 2D & 3D structure of Vascepa or the original EPA. If it has similar activities as EPA in lab and trials so far, then it means at the molecular level that Epeleuton is acting on the same protein target as EPA. In short, EPeleuton has a great deal of scientific value - help researchers track down the protein target which is the holy grail in this case, just like HMGCoA reductase for statins.
That said, I am not sure it has much better commercial value than Vascepa because I imagine Epeleuton likely has a higher manufacturing cost than EPA due to the extra steps for making the 15-hydroxy group. Unless it can deliver much better results in a comparable outcome trial, it doesn't make sense to make it into a commercial product. That's probably why Amarin is not worried. Bhatt can do his research and trials as he is a scientist who lives on research and publications, not revenue and profit.
September 2 is still the fateful date for Amarin.
Good to know. Thanks for sharing. It still has a long way to go.
sts - good to know the EV subsidy dwindles with sales increase. I thought a big chunk of Tesla's revenue is from subsidy in its Q2 earnings. That's why WS is not impressed.
North - talking about speculative. SunHydrogen is still a R&D company. Let's see how its demo project works.
North, sorry I don't have private reply.
I am intrigued by hydrogen fuel cell (HFC) technology. I looked into Nikola for investment recently but decided it's still too speculative at the moment. HFC makes a lot of sense from consumption point of view. But the production and distribution costs are still very high. That can change with technology improvement in the next few years. If Nikola can 1) live up to its promise of its HFC technology, 2)is able to get its freight truck built (not the pickup truck), and 3) sign delivery contracts with some big CPG guys, then it will be golden.
"take advantage"? I hope you meant that Musk just simply knows how to build a product or technology that works better than others.
EV subsidy is for every EV, not just Tesla. NASA contract is open to every space company, not just Space X. All the Big 3 in Detroit, Japan and Germany have been making EVs for years. Blue Origin, Virgin Atlantic, Lockheed Martin, Boeing, Airbus are in the business of making spacecraft, also for years. It's a fair game. The first runner in business typically takes the lion share of the market. It's true for all the markets.
I had questions about the "cleanness" of EV initially. But I think it really depends on your local utility provider. In California, we use PGE mostly. PGE here discloses its energy sources in one of its monthly mailers - 33% renewable (biomass, geothermal, wind, solar), 0% coal, 12% hydro, 17% natural gas, 24% nuclear, 14% others. Hence EV is very popular in CA.
ILT - "One last damn hurdle."
If that's really true, I will stick around. But there is no guarantee that lawsuit like this won't happen.
Me too. Appeal may change strategy around.
I've been a shareholder for exact ten years by now. My return is pathetic. I feel trapped in this stock. So for me, it's more about opportunity cost - if I parlay this money elsewhere, I may have more return. I figure I can be on the sideline for Amarin for a year or two, and see how it performs at the launch. If the market is not as competitive as I thought and the company is able to pull off the GIA (two biggest risks I see), I can always come back.
Of course, if they get sold or bought, I would miss the premium if it's substantial.
Thanks. Case in point. It depends on the insurance reimbursement and the out of pocket fee for each patient. I've seen people posting $9/m (?) on this board.
European market is more universal healthcare or social healthcare. Folks from Europe can comment on this. I gather it's just one contract or price per country, is that right?
My question is - if a market is flooded with cheap EPA supplements (legally or even illegally), are insurances still motivated to reimburse a more costly pharma product. In the US, private insurances are very calculated. Don't know about the EU market.
Not a big fan of GIA. I do not believe Amarin can defend its market even with IPs in place. It only owns labeling not supply. It can't follow a traditional pharma's path. Based on my understanding of the O3 supply chain and EPA biology, I think there will be a lot of market erosion by various unofficial EPA products (not counterfeit, but bona fide purified EPA capsules). In the end, it will be a price war to the bottom as consumers/patients always opt for the lowest price especially for something with pretty low risk profile.
If Amarin keeps this GIA charade which seems it will, I will wait out on the appeal to get off this Amarin train. My goal is to invest in innovation which typically has the highest return and is more exciting (think about Reduce It). This kind of sales marketing game and quarterly earning reports are not exciting to me. Plus I don't even think Amarin is very good at marketing based on their current website and ads.
Hiring a person with a European sounding name and 22-yr relevant experience is a good start. But the risk lies in if this guy can build an experienced team to execute in Europe as I believe he was given an experienced team at Merck. There are just too many cases that a flashy CEO or executive was brought in to do something but failed spectacularly in the end.
The whole EU GIA plan also sounds to me is a hedge for an appeal loss - they will convert to an European company. I guess this is again JT going along with investors or BoD. He is a good fighter. But I want to invest in a general who is in control, not the lieutenants who just follow the order.
JT will likely stay till at least appeal's ruling is out. The way I see it is that Amarin will either be bought or sold after appeal. If it wins appeal, it will be bought out as investors, shareholders and company may not have the stomach to continue riding its rollercoaster. If it loses, it will be sold as what's the point of being stuck with a cost of a pharma but getting a revenue similar to generic's.
Is JT a good CEO? You may have seen this before, an article comparing the returns of investment in Amarin vs. Intuit over the last 27 years. It's graphically disturbing. With or without JT, the company barely delivered anything. JT got an A for scoring ReduceIt and FDA approval, but C for not managing investors and BoD well to sell the company early and hence delivering little shareholder return.
https://www.fool.com/investing/2020/05/09/if-you-invested-10000-in-amarins-ipo-this-is-how-m.aspx
Jasbg - all good :)
Just a tidbit story - the company I worked for in 2010 wanted to hire Adam Ismail, but he declined. If he were hired, he would be my boss, and I'd love to work with him. He is a really good guy.
Jasbg and Rose -
"largely" to me (and you) means the standard deviation is big. It's understandable because DS products don't have as a stringent quality check and assurance process as drugs.
I don't want to spend more time on the oxidation discussion than what I have already done. As an investor, I am happy that you all think Amarin has a better capsule. Amarin needs every bit of differentiation they need. Kudos to the company. However as a scientist (or at least used to be), I will take whichever is cheaper - Vascepa or a 98% EPA drug in a non-Amarin capsule (before the expiration date). To me, they're essentially the same.
One last comment on this - Vascepa needs a lot of marketing dollars and efforts to truly stand out because the differentiation is elusive. Hence it needs to be sold by a party with deep pocket and a companion drug (i.e., statin) so it can sell one at low margin to improve the sales and margin of the other.
I won't comment on oxidation anymore. Have fun.
Jasbg - have you read the article before making the comments?
Cut & Paste below the funding and authors of this article. I met Adam Ismail personally in 2010. He is a very respectable person and I have high regards to him. I remember he was the chairman of GOED back then, a well respected governing body of O3 industry (a non-profit one).
I believe encapsulation technology has drastically improved over the last ten years. Oxidation is a concern, but far from a show-stopper from taking O3 or Vascepa. Unless you show me the side-by-side comparison data of O3 vs Vascepa oxidation over time, I wouldn't think Vascepa capsule is that superior to O3's especially those of the high-end ones by Nordic Naturals, etc. That said, capsule is often used by marketing folks to make audience think it's different and better, but rarely substantiated by solid scientific data. After all, encapsulation is all outsourced to third party encapsulators and there are only a handful of them out there. I believe Amarin uses Banner which has contracts with many other O3 brands.
5. Conclusion
This study has found that the 48 EPA/DHA omega-3 dietary supplements with the largest market penetration in the U.S. largely complied with the industry limits for oxidative quality of EPA/DHA oils set voluntarily by producers and finished products manufacturers. Most products adhere to the FDA requirement that natural ingredients should contain at least 80 % of the labeled content. It is nevertheless challenging to evaluate the compliance for products sold in the U.S. given the lack of government regulations on oxidative quality specific to dietary supplements, and content labeling requirements that are currently not clear. This study highlights the variety of omega-3 LCPUFA products available to consumers, some methodological limitations associated with currently available products and formulations, and the importance of taking into account analytical variability when reporting on compliance. Good product storage conditions are suggested based on absence of correlation between the chemical markers and the product expiration. Room for continued improvement in quality of EPA/DHA finished products in the U.S. is however suggested since nearly half of 17 tested products for which all quality parameters could be tested did not meet at least one of the oxidative quality criteria or the label claim for EPA + DHA content.
Funding
The purchase of products and shipping costs were financed by GOED. Laboratory services and materials were provided by each of the participating laboratories. G.B., H.R. and A.B. are employees of GOED. A.F., C.M., L.N., R.H., J.I., K.P., L.L. and A.I. are employees of companies that are members of GOED. A.I. was an employee of GOED at the time the study was conducted. S.W. is an employee of UC Davis, and A.P. was a M.Sc. student at UC Davis supported by funding from the Department of Chemistry at UC Davis and GOED.
Author contributions
A.B. and A.F. analyzed U.S. market data. A.I. collected finished products and organized sample distribution to the different laboratories. A.I. and G.B. coordinated the study. C.M., L.N., R.H., J.I., K.P., L.L., A.P. and S.W. performed chemical analysis and data analysis. G.B. and A.I. analyzed results and wrote the manuscript. H.R. provided input on regulatory aspects. A.B. provided input on statistical analysis. All authors revised the manuscript.
Declaration of Competing Interest
G.B., A.B. and H.R. are employees of the Global Organization for EPA and DHA Omega-3s (GOED), a 501(c)6 not-for profit trade association. A.F, C.M., L.N., R.H., J.I., L.P., L.L., and A.I. are employees of manufacturers of ingredients and supplements, and are members of GOED.
Acknowledgements
The authors thank the analytical laboratories for their collaboration and independent analyses. Vangie Lund is acknowledged for helping with sample organization.
North, Eight and Marjac - second Handmanw's, really appreciate your sharing your knowledge and experience of the legal system with us!
Eight - thank you so much for the elaboration! The process is now clearer to me. All make sense.
Hope I am not too presumptuous to say this - sounds like judge's opinion of a case is already formed before oral argument (naturally). The hearing, deliberation and opinion write-up are just firming up that opinion.
It'll be fascinating to see/hear the dynamics among different parties in that fateful hour!
Marjac - Thank you so much for explaining the appellate process! It's fascinating.
Marjac, Eight - Question regarding the appeal process. Apologize if these have been asked before.
You commented that the ruling can be released anytime after the oral argument is done, i.e., from Sept 3 to Q1, 2021.
My curiosity is why it can take so "long", i.e., four months or longer? Do the assigned judges only work on this one case all this time (unlikely)? or they all juggle multiple cases at the same time (most likely). If so, I gather the time is subjected to how judges prioritize their case load. Also, do the three judges review the case collaboratively, i.e., discuss or debate the points together? or completely independently and each will give his/her vote in the end? Is there a deadline for them to send their vote in? or they can take however long they need, and the court will just wait till all three votes are in to reveal the final ruling.
This is all new and interesting to me. I'd like to learn more. Thank you very much for helping me understand it! If these questions have been asked before, please let me know and I will search the board.
Interesting. If he reads this board, then he may post on this board too. Wondering under which alias, hmmmm... Shall I rule you out? LoL.
Just kidding. It's a Sunday joke. Thanks for sharing this, BB.
BB - I assume the "he" in your post refers to JT. If so, are you sure he/JT reads this board? Did he imply this in your two's email correspondence?
I never doubt the identity of that email. It reads like JT's style too, to me.
CEOs do reply emails from retail investors and users/patients on their own without their IR team's filtering unless they're Elon Musk. They don't reply all emails, but do to some that caught their attention. Steve Jobs did it, Jeff Bezos did it. Musk is very active on Twitter communicating with users and followers even after the SEC's "ban".
It's nothing out of ordinary. I think it's nice that JT replied to that poster and it's also nice that the poster shared it on this board, though it sounds that he probably should get JT's permission first. Still I thank him for sharing.
Postes - those are good questions. But I am not sure we will get to know the answers soon or ever.
Obviously, there are things that exec's cannot legally say in public. A good friend of mine used to work in investor relation of a large tech company whose CFO is a very well respected executive among WS analysts because he likes to break down the true message which he is not allowed to say directly, into puzzle pieces and hand over piece by piece at different times during the earning calls. Smart analysts can then piece those together on their own and get the message. We all know JT's communication style. If he can share, he will share. If he can't, he won't. Since articulation is not his strength, he just stays away from it.
Since you mentioned the 2019 events, it makes me think if he anticipated such risks back then and hedged them using the last secondary. He was definitely quite proud of having $600M in the bank on the investor call in April.
Enough speculation for a day from me!
sts66 - in these three key sentences, investors are mentioned three/four times and in every sentence. Unless JT is trying to point fingers, it seems clear at least to me that investors have a say here.
We listened to input from many investors over the past several years. Such input included suggestions on what would be settlement terms that they (investors) would accept. The settlement terms that were suggested by investors were not available and we emphasized (implying "to investors") for many years that the courts can be unpredictable in such matters ...
Postes - so what do folks on this board want to hear from JT assuming that JT can speak freely?
What kind of settlement terms H&R want? or if there is any BO offers? and terms?
It will be really nice to have this info. But we know that he can't share any of these.
What he wrote in that email seems harmless to me. But I am pleasantly surprised that he took the time to reply a retail investor (I assume jwjones62 is one of us, not a major shareholder). I gather he must be just as frustrated as us.
Postes, my interpretation of JT's words (FWIW):
assumes that a settlement was available on terms that you would not have been similarly disappointing
The settlement terms that were suggested by investors were not available and we emphasized for many years that the courts can be unpredictable in such matters
JT's email didn't provide much new info to us, IMO. It just confirms what many of us have already suspected or expected:
- yes, there was settlement discussion(s). Why not, Amarin settled with Teva and Apotex; isn't it a common practice for a brand to at least have one settlement conversation with generic challenger before taking them to court. That's why JT felt comfortable to imply it in the email.
- yes H&R's terms were not acceptable to Amarin; Of course, if they were, we wouldn't be in Nevada court.
- yes, Amarin knew the legal risk but still rolled the dice.
The only info that we didn't expect so much is "not settling but suing generic" was a decision made and agreed upon by all - the management, major investors and board, and it sounds to me that JT may not be in full agreement with investors on not settling based on his comment "we emphasized for many years that the courts can be unpredictable in such matters". But he went along with the investors, and now is dealing with the consequences. That's probably why he is still the CEO.
Yes, TSLA does direct distribution without middleman/dealers. Mainly through web orders and delivered to your door. They do pre-order and then manufacture for the order and then delivery. So build-to-order, similar to the Dell production model in the early days. No inventory holding cost, ...
I believe they have some kind of arrangement to connect a potential buyer with an existing owner nearby to showcase the car. Pre-COVID I think they may have even opened a few showrooms for folks to drop by and see, test drive the vehicles, similar to dealership but mainly for showing purpose, not selling.
They're the only cars that are still selling in the COVID time. That's precisely the reason catapulting its sp.
Plus, its China factory was only shut down for a month or so. The demand in AsiaPac is very high.
Ranked by US News as #1 in the luxury & EV category. Not surprised by the quality issue identified by JD Power as their production is racing to catch up with the demand - just part of the growth pain - a good problem for company, but not so good for users.
The risk I see is Musk's over-confidence in autonomous driving, which could lead to big problems, legal problems.
OT. My estimate for TSLA is $2000 year end. And I am more confident on this than on AMRN winning appeal :) China is the driver.
What's happening tomorrow AM?
TSLA Q2 numbers should be good based on their delivery numbers. Still it's probably baked in the sp already.
The company is on fire. Growing market + 5-year ahead of competition + great products + strong brand + smart CEO + software + data + SolarCity + charging network + global factories & distribution channels
Where else can you find such a package? Nowhere.