Amarin Corp Plc (AMRN)

[IgnoranceIsBliss]

They should run a 12-week trial in Europe for this indication -- from design to publication that ought to take a year

[Whalatane]

Here are some examples of real-world evidence (RWE) studies that supported the approval of drugs in the EU:

The European Medicines Agency (EMA) has published several case examples of how RWE was used to support marketing authorization applications for new products and extensions of indications submitted to the Agency in 2018 and 2019:
40% of initial marketing authorization applications contained RWE to support the applications.
18% of applications for extension of indication for products currently on the market contained RWE.

The report describes the characteristics of the RWE included in these applications, such as using electronic health records, claims data, and post-marketing safety reports to support clinical efficacy and safety in new patient populations.
Additionally, the EMA has conducted various pilot studies to explore the use of RWE to support regulatory decisions across its scientific committees and working parties.

Some examples of these RWE studies include:
Safety studies
Drug utilization studies
Disease epidemiology studies
Studies to inform the design and feasibility of clinical trials
Studies to support health technology assessment and payer decision-making

These EMA-led RWE studies have covered a range of therapeutic areas, with a focus on conditions diagnosed or medicines used in the primary care setting. The learnings from these pilots are helping to establish the value of RWE and identify the regulatory use cases where it can add the most value alongside traditional randomized clinical trials.

EMA has initiated 30 RWD studies since September 2021, with 27 of them completed by February 2023. These studies covered topics such as safety, drug utilization, disease epidemiology, and informing the design and feasibility of clinical trials.

The studies were conducted through three main pathways: 25 studies led by EMA, 4 studies initiated via the DARWIN EU® network, and 1 study commissioned to one of EMA's research organizations.
The RWE generated from these studies was used to complement evidence from other sources, such as clinical trials, to support regulatory decisions by EMA's scientific committees, working parties, and national competent authorities.

Examples of how the RWE studies were useful include: filling knowledge gaps, validating evidence submitted by companies, providing additional information like recent data or data from different regions, and conducting sensitivity analyses.
While most studies focused on conditions and medicines used in primary care, about a third of the research topics were not considered feasible due to limitations in the available data sources or procedural time constraints.
In summary, the search results indicate that EMA has actively leveraged RWE from its own studies and the DARWIN EU® network to support regulatory decision-making across various use cases, though some challenges remain in terms of data availability and timeliness.

Kiwi

[Snd101]

Definitely not run another trial for CVD indication (re establish reduce-it outcome), if that is what you want to know.

[biofalcon]

When selling a new drug, you don't signal a loss of confidence in your research, the results, or the product by doing another trial. If you show weakness in your convictions and product, it will only create further doubt in the minds of the people you are trying to convince. When selling, conviction, persistence must prevail.

[IgnoranceIsBliss]

Anybody know if Amarin holds any European patents on this indication (headaches)?

[ORBAPU]

Do you know if CNC GELCAPS produces branded EPADEL or a generic?

[IgnoranceIsBliss]

No surprise that a systemic anti-inflammatory would help with migraines

Add joint pain, gastrointestinal issues, maybe gout, who knows…

[IgnoranceIsBliss]

Huge market (obvs)

https://www.nature.com/articles/d41573-023-00182-x

[Jasbg]

JR, If you say the same thing 5 times each month - year in and year out - you can still call 'debating' !

If you repeat it 2.000 times a year - it is like Coke adds - deliberate 'Brainwashing' atemth.
---------------------------

Over the years ? - You been here since early 2022. You missed like 17.000 post: "Amarin need more trials" - because Whala says so !

[DMC8]

The science is very clear, Vascepa does wonder for heart and brain, the 2 most important organs of human body.

[CorkGilly]

We need a scientist to comment ….but looks like primary endpoint is a 5x increase in fatty acid post-use….which I believe is positive as the higher level is better wrt cancer…..🤔

[Triple88]

Capt
Thanks for sharing !!
Looks like this would be worthy of a Press Release if our partnership with Mochida covers Epadel & patents for this potential indication ??

[JRoon71]

Interesting that they have not updated ClinicalTrials.gov for the outcomes.

[CaptBeer]

Thanks for the post. Here's a recap + ClinicalTrials.gov website:
$AMRN More info on the Taiwan RCT to reduce migraine frequency & severity with high dose EPA (EPADEL):
Here is the Peer Reviewed Publication:

https://www.sciencedirect.com/science/article/pii/S0889159124003003?via%3Dihub
Here’s the ClinicalTrials website:

https://classic.clinicaltrials.gov/ct2/show/NCT04572789

The primary outcome was the decrease in migraine attacks over a 12-week period & the severity. Several Secondary Outcomes are listed in the publication.
It appears that many Outcome measures were met with significance including the Primary:
Comparing baseline values to those at week 12, the EPA group displayed significant improvements in various parameters within the group, including a marked reduction in monthly migraine frequency (7.4 ± 5.0 days vs. 3.0 ± 2.0 days, p < 0.0001), decreased usage of acute headache medication (2.9 ± 3.2 days vs. 1.6 ± 1.7 days, p = 0.013), lowered headache severity (VAS score: 5.5 ± 2.0 vs. 4.2 ± 2.6, p = 0.004),

[newman2021]

They took only 2gm daily; half of the Vascepa dose for the heart problems. And it still helped the migraine patients. Interesting.

[Birdbrain Ideas]

Seems like a study that might give doctors favoring fish oil supplements even more ammunition to support their bad choices since the study used a product, "crafted by CNC GELCAPS CORPORATION—an entity accredited with ISO 22000, HACCP, and GMP standards—(which) incorporates an orange flavoring agent to conceal the taste of EPA."

[DMC8]

Amarin to Present at H.C. Wainwright 2nd Annual BioConnect Investor Conference
Date/Time: May 20, 2024, 4:30 p.m. ET

Webcast: https://journey.ct.events/view/a719062a-400f-406f-82d4-2463ef546624

https://www.marketscreener.com/quote/stock/AMARIN-CORPORATION-PLC-1658813/news/Amarin-to-Present-at-H-C-Wainwright-2nd-Annual-BioConnect-Investor-Conference-46636316/

[DMC8]

A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine
May 2024
https://www.sciencedirect.com/science/article/pii/S0889159124003003

[CaptBeer]

The 1.8g capsules described in this article tells me that the drug used in this trial was EPADEL. I also assume Mochida has a MOU patent on this indication? Would this indication fall under our IP sharing contract with Mochida in the US or other territories? I’ll do some homework on this today.

[CaptBeer]

That’s a new one. Thanks for sharing.

[DMC8]

EPA in fish oil prevents migraines
By: Dr. Mauskop
05-05-2024
https://www.nyheadache.com/blog/epa-in-fish-oil-prevents-migraines/

[Nukemtiltheyglow]

No problem, I guess I wasn’t following all of your posts. IMHO, I think Denner & Holt are working hard to wright the ship.

[Number sleven]

JRoon, Good advice. I doubt he takes it.
Sleven,

[Whalatane]

Based on the search results provided, it does not appear that tax loss credits for a company registered in Ireland can be directly used by a company registered in the US. The key points are:
Irish resident companies are generally taxable in Ireland on their worldwide income and capital gains, with a credit available for foreign taxes paid.
Foreign taxes borne by an Irish resident company may be creditable in Ireland, with a system of onshore pooling of excess foreign tax credits available.
However, the search results do not indicate that tax loss credits from an Irish company can be directly utilized by a US-registered company. The tax systems operate independently.
The search results suggest that the tax treatment and ability to utilize tax credits is specific to the company's tax residency. There is no mention of a mechanism to transfer tax loss credits between an Irish company and a US company. The tax systems appear to be separate, with each company subject to the tax rules of their respective jurisdictions.

Do U use Perplexity ?

Kiwi

[JRoon71]

Is anyone familiar with how this would be handled with a potential acquirer from another tax jurisdiction (country)?

"This excluded the unused $1.6B tax loss credits" .I'm sure a BP would know how to recover this money.This alone gives a value of about $4 per share.

[JRoon71]

Jasbg, just because people disagree or don't get on board with whatever you believe, or don't worship at the feet of Denner, does not necessarily mean they are shorts or have nefarious motives.

I don't necessarily agree with everything Kiwi says. I also don't agree with some things that a lot of posters say (And i know plenty of people don't like what I say). But sometimes you can learn something from people you don't agree with. Even if it's just small nuggets of wisdom. I have learned quite a bit from Kiwi over the years, despite not necessarily being on board with all that he says.

I don't believe that more trials are the answer right now (for EU). Kiwi does. But it doesn't mean I ignore him or bash him.

If you don't agree with what someone says, either give your constructive feedback, seek more explanation, or simply don't respond.

[Whalatane]

Chromosome And I completely agree with your analysis , assuming they mine the data Kaiser etc are accumulating .
Make the economic argument in the EU for the reasons you mentioned.
The RR in select subgroups such as Revasc doesn't have to be as high as R-IT in the RWE study ...it just needs to be clinically relevant and a cost effective use of the Health Dept funds. ...( ie The Health Dept will save Euros by reimbursing for the sub group studied )

Kiwi

[Snd101]

Sure Kiwi,
Amarin will conduct/fund trial to get the so called real world data (same data acquired via reduce-it trial), just because it is your fantasy.

Similarly Santa will deliver a unicorn 🦄 to me this Christmas, that I will ride to work every day. And yes, this unicorn will be very special as it poops pure gold.

All very practical.

[FlyFishingStocks]

He gets under your skin because he’s right on many counts and you know it. He remind you, monk, caddied, etc. of what a colossal mistake this investment has become.

To think honoring a down trendline could have avoided all this. Wow.

[Chromosome]

Kiwi yes I think you are making my point. It doesn’t have to be exactly the same outcome as the trial; this is an economic argument and works better in European countries because there is a single payer systems and people don’t change insurance. In the US, economic incentive is more focused on short term for insurance companies as people are switching insurance more of term (at least for the commercial insurance). You can argue Medicare is a single payer system for the elderly. They can easily compare two cohorts; one on V and one not on V and look at the last say 5 years and see how many CABG’s or PCI’s each cohort got (have to be pretty similar patient characteristics). I think with RWE mounting, even Germany will come on board, eventually. Just my opinion

[Whalatane]

So what would constitute a stronger dossier ...Real World Evidence studies that the previous mgt once floated ?

As you probably know ..Real World evidence studies rarely show the same degree of RR as the original trials.
This is well known and the reason is that in most CV trials the patients that enroll are often more health conscious than the general public and are more likely to adhere to the dosing schedule.

So knowing this you focus on that subgroup with the highest RR thats quantifiable and can easily translate into healthcare cost savings .
Even if the Revasc subgroup only showed a 20% RR vs the over 40% reported in R-IT ...its still a huge saving in healthcare cost .

Ask posters here who have had a PCI what they cost ?
My angiogram / angioplasty in 2016 was $18,000 ...no over night stay and no stents
This didn't include the ER costs ...just the Cath Lab costs
One of my business partners had several stents , in hospital for 2-3 days I think ...close to $100,000

Kiwi

[CaptBeer]

If my suggestions counted for anything I would be the CEO. They’re the experts and we pay them to move the ball forward. I won’t back-seat quarterback. They’ve resubmitted in Italy and France (which have already passed the technical assessment) and they continue to gather evidence for Germany.

[Chromosome]

I don’t think the answer is more trials…the answer is better promotion, stronger dossier for reimbursement and patience. Just my opinion.

[Whalatane]

Capt. The issue is how to obtain reimbursement in the remaining big 3 EU markets and spark an increase in script numbers in the existing EU / UK markets .
The current strategy ...same ol same ol ...isnt doing it ( Spain being the possible exception ...but still only 2,000 scripts IIRC )

So what's the boards ( and your ) suggestions for gaining reimbursements and increasing script number in these markets ?

Kiwi

[Jasbg]

Monk, He's been on ignore for years !

Problem is' that on iHub - he's posts still turns up on your screen - when answering other posters - you follow.
---------------------------------------------------------------------

I have pointed this out to iHub leadership (putting people on ignore - as of now - is an illusion) - something iHub hopefully will address, at some point !

[Monk4444]

Kiwi’s MO is to piss you off and get a response. Put him on ignore as I’ve done long ago and. Just don’t give him fuel
If he can’t piss anyone off anymore he’ll go away

[CaptBeer]

My comments were in the context of the previously posted article:

“Lipoproteins, Cholesterol, and Atherosclerotic Cardiovascular Disease in East Asians and Europeans.” https://www.jstage.jst.go.jp/article/jat/30/11/30_RV22013/_html/-char/en

The JELIS Trial has over two decades of Evidence and over a decade of Rx exposure in Japan. I’m pretty damn sure if EPA was a “false positive” and had no clinical benefit, as that numbskull Nissen said, it would have been removed from the market. When in fact after 10 years of generic competition it still enjoys 60% market share.

Yep! They’re convinced in Japan, and apparently in China too as they are not requiring another outcome trial for CVD. I don’t have any knowledge regarding what South Korea, Malaysia, or Thailand may require but I also doubt they would require another outcome trial.

[Jasbg]

caddiedad, And who other than Whala (+20.000 posts - trying to undermine Vascepa and the Reduce-It trial) !!!

What are his motives for using 'these endless hours on a subject - of 'officially' no personal economical interest to him ????
---------------------------------

And referring crap like this - is an insult to every honest and serious poster on this board:

Some experts, like Dr. Steve Nissen, felt the many limitations of the RESPECT-EPA trial made the results uninterpretable and that it should not be used to support the data from the REDUCE-IT trial.

[caddiedad]

Thanks Dr. Steve for your concern and bashing of V over the years. Scorned much?

[Whalatane]

Based on the search results, here are the key things Amarin would need to do to get reimbursement for Vazkepa (icosapent ethyl) in Germany:

Reach a viable agreement with the National Association of Statutory Health Insurance Funds (GKV-SV) on the reimbursement price for Vazkepa:
The search results indicate that after four rounds of negotiations, Amarin and the GKV-SV were unable to reach an agreement on the reimbursement price.
The matter was escalated to the Arbitration Board for a final decision, as the two parties could not come to terms.

Potentially use real-world evidence and data to support the clinical benefits of Vazkepa:
The search results mention that there is a precedent in Germany where a product that received a negative reimbursement decision was able to get it reversed by using real-world evidence and data to demonstrate the clinical benefits.
Amarin indicated they may explore a similar path to resubmit the file in Germany.

etc
Kiwi

[Whalatane]

The key criticisms of the RESPECT-EPA trial were:

The trial was underpowered and failed to meet its primary endpoint of a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina requiring hospitalization, and coronary revascularization. The reduction in this endpoint was of borderline statistical significance (p=0.055).

The trial had a high number of patient withdrawals or protocol deviations, which added uncertainty to the conclusions.

The open-label design, without a placebo control, was a limitation that could have introduced bias.
While the trial showed a signal of benefit consistent with previous trials like JELIS and REDUCE-IT, the magnitude of the potential cardiovascular benefit was uncertain.

There were concerns about the increased risk of atrial fibrillation seen with icosapent ethyl, which could offset any potential cardiovascular benefits.

Some experts, like Dr. Steve Nissen, felt the many limitations of the RESPECT-EPA trial made the results uninterpretable and that it should not be used to support the data from the REDUCE-IT trial.

In summary, the RESPECT-EPA trial was criticized for being underpowered, having design limitations, and failing to provide definitive evidence on the cardiovascular benefits of icosapent ethyl, despite showing a signal of potential benefit.

Kiwi

[CaptBeer]

See my previous comment. There's no sense in re-beating that Dead Horse.

[Whalatane]

EPA not EPA+DHA could be beneficial ;however, further investigations are needed

,,,where have we heard that before and what would they be ?
Kiwi

[CaptBeer]

As an additional comment to this conclusion by the authors, I don't believe that additional RCT's are needed to prove the efficacy of IPE. They didn't mention the results from RESPECT-EPA another Japanese RCT that showed a 26.6% RRR in secondary prevention (p=0.03), and a 21.1% RRR in Primary Prevention (p=0.054). Furthermore, there's been a bunch of recent studies to support that it's not Just about LDL-c, ApoB, Lp(a), TG's, or the placebo.

It's the EPA Stupid!

[CaptBeer]

RCT's in East Asian Populations have shown a "causal association of elevated remnant cholesterol with increased risk of ASCVD."

"In the East Asian context, in the JELIS trial with 18,645 Japanese individuals with hypercholesterolemia, EPA on top of statins showed a 19% relative reduction of major coronary events. From these results as well as the results from the REDUCE-IT trial, EPA not EPA+DHA could be beneficial; however, further investigations are needed to conclude the efficacy of omega-3 fatty acids."

[MA52TA]

"This excluded the unused $1.6B tax loss credits" .I'm sure a BP would know how to recover this money.This alone gives a value of about $4 per share.

[DMC8]

https://www.jstage.jst.go.jp/article/jat/30/11/30_RV22013/_html/-char/en

[DMC8]

Extract from latest Q1 2024 10Q.
Sum up accounts receivables, current & long term inventories, AMRN has additional about $445m total assets on the balance sheet, on top of the cash on hand $308m.
This excluded the unused $1.6B tax loss credits.

With 410m shares float, AMRN’s intrinsic value is way much higher.

Not forgetting China’s rapid TG uptake of 100% growth on debut quarter. China will be the largest big bang for AMRN, both in terms of supply clearing and BO valuation.

[Snd101]

Dear Kiwi,
Every one agrees with all the concerns that you mentioned here in this post. No one is ignoring them.

What I don’t agree is you saying management is not doing anything to address it. And that they are just waiting and watching and in the interim their only plan is to use the $50Mil buy back to support the SP. That acquisition is as naive as it can get.

And of course you also know it very well that Amarin is not going to spend money to run another trial to revalidate reduce-it outcome, which you keep pushing for. Because that would be the most ridiculous thing for Amarin to do.

[Number sleven]

Nuke, I think you misunderstand my post. Kiwi is criticizing our current management for not running more clinical trials. I am actually defending both current and past management. I think it would be a waste of money to run any more trials to prove the value of icosapent ethyl for cardiovascular risk reduction.
Do you disagree?
You made your decision about who you think should be running the company, and your not whining about what they are doing. I have no problem with what I have seen current management do to date.
Sleven,