Update on Mochida MND-2119 new formulation approval

Today I noticed "Stage = Approved" for MND-2119 on Mochida Pharmaceutical Co., Ltd.'s Research & Development Pipeline page "As of August 1, 2022"
https://www.mochida.co.jp/english/business/rd.html
Have not seen any press release, and to my best recollection, last time I checked it was just listed as "filed".

https://pj.jiho.jp/article/244669
"Mochida Pharmaceutical said on June 22, [2021] that it has filed for the Japan approval of MND-2119, a once-daily soft capsule version of its high-purity ethyl icosapentate (EPA) agent Epadel (ethyl icosapentate).This is an upgraded formulation of Epadel that is intended…

From May 13, 2022 document The Mochida Pharmaceutical Group's "22=24 Medium-Term Management Plan", p. 6: "2.3. Business Strategies... ii) Development ...- To obtain approval during the 22-24 Medium-term Management Plan period for MND-2119, a
new highly purified EPA drug" and p. 7 ...iii) Marketing ... "- In the cardiovascular area, to promote propagation of the value of Urece, a treatment for
hyperuricemia in gout; Also, to focus on early maximization of sales of MND-2119, a highly purified EPA drug, by leveraging our experience as a leading manufacturer of highly purified EPA drug;"

Recall recent publication (June 24, 2022): "Efficacy and safety of self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (MND-2119) versus highly purified eicosapentaenoic acid ethyl ester in patients with hypertriglyceridemia: Results from a 12-week randomized, double-blind, active-controlled, phase 3 study"
https://pubmed.ncbi.nlm.nih.gov/35871058/
https://www.sciencedirect.com/science/article/pii/S1933287422001817?via%3Dihub
concluding from trial:

Happy Birthday, Monk.

I agree with you re TA limitations here, too.

dogn

I have a healthy respect for technicals, look often at resistance/support levels, RSI, short & long term moving averages, MACD. But let's not use them on a message board where there appears to be an agenda to spread FUD. Let's put into context when some technical upthrust breaking some average and falling occurs on an unusual day, that of the earnings report. I may be wrong, but don't think there's much more downside to be had (except perhaps on short time frame). I prefer long term buy and hold with minimal trading around core position, and have added 4000 at today's lows (now 24K shares), believing with Birdbrain Ideas post #385070 (below) that all the negative news and very few upcoming positives are baked in. Today is shorts attempt to drive down price after rally as market digests rather negative past quarter without looking forward to revenues ramping up in multiple countries over year ahead.

I also take issue with FFS excessive use of "LOL" as he mocks and belittles others... that particularly makes it hard to respect his practices and habits lurking on this board when things look most dire, spreading FUD to help him catch his next swing trade. Why is this the only iHub stock he ever posts about? What boiler room is he working for? He may now add me to his S list.

dogn

Something else for your TA toolkit
https://www.tradingview.com/blog/en/new-product-launch-trader-tarot-cards-23658/

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Stay tuned for more releases, including trading desk crystal balls, coming very soon.

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Perhaps an update or announcement tomorrow on BP partnership for ROW (outside EU) as hinted at twice in the May 25 H. C. Wainwright Global Investment Conference interview:

“And that's what's attracting many of the third-party Big Pharma partners with whom we are negotiating at the moment because we do not intend to go ourselves to any of these international markets outside of Europe, right?

It's 20 additional markets, we believe we need to focus on what we can do, which is Europe, we are having an agile, efficient model by which we can be very efficient and commercializing in Europe but once you go to those international markets, it is very difficult to stay efficient because you cannot centralize business. We're doing so many things out of Zug in Switzerland which you cannot do. You can do then a hub in Asia, a hub in Latin America, but you multiply your costs. So that's not the way to go. And we are very actively engaged with a number of big pharma potential partner at least for Asia, which are the markets that are going to get regulatory approval by end this year.”

Amarin Corporation Plc (AMRN) CEO Karim Mikhail on H.C. Wainwright Global Investment Conference (Transcript) https://seekingalpha.com/article/4514526-amarin-corporation-plc-amrn-ceo-karim-mikhail-on-h-c-wainwright-global-investment-conference

Thank you for this explanation, Dukesking

Dr. Reddy’s antitrust case mentioned in this WINSTON & STRAWN LLP “Monitoring the Vitals of Health Care and Pharmaceutical Antitrust Enforcement” interview Jul 26, 2022

COMPETITION CORNER

What do companies operating in the health care and pharmaceutical sectors need to know about antitrust enforcement? In this Women in Antitrust episode, Host Kerry Donovan sits down with Partners Neely Agin and Heather Lamberg to talk about current trends. Neely covers the latest developments in hospital mergers as well as recent moves to enhance scrutiny of pharmaceutical deals. Heather discusses some of the key class actions and competitor lawsuits facing health systems, as well as the pharmaceutical antitrust cases everyone is watching.

[Is everyone really watching this? -dogn]

https://www.winston.com/en/competition-corner/monitoring-the-vitals-of-health-care-and-pharmaceutical-antitrust-enforcement.html

From near the very end:

Kerry Donovan: That’s really interesting. And so, Heather, what about on the litigation side? Have any sort of these novel approaches been advanced in the world of antitrust litigation in the pharmaceutical space?

Heather Lamberg: There’s a variety of different issues that percolate in the pharma litigation area. I thought I would just highlight a couple of cases that everybody’s watching on some of these issues.

For example, there is a case that was brought by Dr. Reddy’s against Amarin. And the allegation there is that Amarin entered into a whole host of exclusive dealing arrangements with the API—the active pharmaceutical ingredient—suppliers, and in doing so, they basically made it impossible for Dr. Reddy’s to get the key ingredient to make a generic version and delayed entry. That case is still in early stages, pending. It’ll be very interesting, because from an antitrust perspective, it raises all sorts of interesting questions as to whether they’ve substantially foreclosed an API market, whether there is an API market, etc. Most of the cases that have raised these types of allegations have ended up settling. So, we don’t have a lot of decisions in the space.

Similarly, you have a case that Teva has brought, which is quite similar but different. There is new legislation out there that basically gives a generic company a private right of action to sue the branded if the branded company refuses to give them a product sample. So, in order to sell a generic, you need to have a product sample from the branded to test that your generic is bioequivalent to it and get FDA approval. If they won’t give you a sample, you can’t show you’re bioequivalent to it. And that has been a tactic of some branded companies to say, “I have no obligation to help my competitor. I’m not giving you a sample. Figure it out yourself.” And it hasn’t been successful prior, but now we have this legislation, and Teva has filed a lawsuit under it for the first time. So we will see how that plays out as well, which is an interesting development.

Kerry Donovan: Thank you so much, Heather. This has been a very interesting conversation. I really enjoyed getting to talk to both of you, hear both of your points of views about these issues.

[interesting comment above that “in order to sell a generic, you need to have a product sample from the branded to test that your generic is bioequivalent to it and get FDA approval. If they won’t give you a sample, you can’t show you’re bioequivalent to it.” Many here have assumed FDA didn’t evaluate generic Vascepa… certainly they didn’t require a cardiovascular outcomes trial, but it would be interesting to know more about what testing they did for bioequivalence.]

Banned in Europe effectively Aug 7, but only from food. Pharma manufacturers have 3 years to transition to safer alternatives.

https://blog.capscanada.com/titanium-dioxide-why-your-capsules-should-be-tio2-free

Posted by CapsCanada on 16-May-2022
“The European Food Safety Authority (EFSA) has now classified titanium dioxide (TiO2) as an unsafe food additive. As a result, TiO2 is being banned in Europe in products meant for human consumption, with some of the bans going into effect in Summer 2022:

“Titanium dioxide as a food additive – Following a six-month transitional period that began on February 7, 2022, a ban on the use of TiO2 as a food additive in food and food supplements sold in the EU will go into effect on August 7, 2022.

“Titanium dioxide in medicines – The pharmaceutical industry has been given a bit of a reprieve. Right now, the ban only applies to food. The European Commission has stated that pharmaceutical makers can continue to sell medicines in the European market that contain titanium dioxide for at least another three years. After that you must either find alternatives or justify why titanium dioxide should continue to be used.”

However, it seems the more widespread use of TiO2 in drug capsules is as a pigment to make the capsules opaque. As Vascepa/Vazkepa uses a CLEAR capsule, I assume the quantity of TiO2 (apparently used only to print the brand name) is extremely & incomparably small and not hazardous as it might be in opaque capsules using much more of it.

https://www.drugs.com/inactive/titanium-dioxide-70.html

The lettering on Vascepa/Vazkepa capsules may be printed via UV laser, in which case the capsules could eg contain ~3.5% TiO2 as reported in https://pubmed.ncbi.nlm.nih.gov/23786207/

Imprinting on empty hard gelatin capsule shells containing titanium dioxide by application of the UV laser printing technique
Akihiro Hosokawa et al. Drug Dev Ind Pharm. 2014 Aug.

Vazkepa uses titanium dioxide for the printing ink. From EU data sheet p. 10. No generic in Europe. Relax folks, this is not an issue.

https://ec.europa.eu/health/documents/community-register/2021/20210326150935/anx_150935_en.pdf

Average cost basis of institutional owners of AMRN stock

From https://whalewisdom.com/stock/amrn, downloaded spreadsheet of Q1 2022 institutional holdings (latest available with Q2 2022 "not compiled yet), showing 217 funds holding total of 127.49 Million shares (32.1% shares outstanding), in close agreement with Fidelity's reported 33.1% institutional stock & mutual fund ownership.

Using Whalewisdom's "Estimated Avg. Price Paid" (and Sarissa Capital cost basis of $4.455 from post #367308 (data omitted by Whalewisdom when last 13D amendment filed), calculated average cost basis for all institutional holders of $6.10 per share, 4.59X above todays asking price. On average, institutional holders are down -78.2%.

For Top 10 institutional holders (holding 22.2% of outstanding shares), average cost basis is $6.19 per share).

About 60 of these institutions list a Source Date of 2022-06-30 (Q2) and "Date Reported" in July 2022... updates for Q2 22 still rolling in (3 today).

Also note that SCP Investment, LP dropped from 4th largest institutional investor with 6.75M shares to 12th largest with 2.75M shares after selling 4M shares (not sure when – Source Date 2022-06-30, Date Reported 2022-07-28).

Above numbers provide me some perspective on my current breakeven cost of $4.44 (20K shares).

dogn

Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements
Michael Miller et al. Expert Rev Cardiovasc Ther. 2022.

Expert Rev Cardiovasc Ther. 2022 Jul 28;1-17.
doi:10.1080/14779072.2022.2103541. Online ahead of print.

https://pubmed.ncbi.nlm.nih.gov/35876118/

Abstract

Introduction: REDUCE-IT demonstrated that adding 4 g/day of icosapent ethyl (IPE; purified ethyl ester of eicosapentaenoic acid [EPA]) to statins substantially reduced cardiovascular disease (CVD) events, with few adverse effects. These data prompted numerous leading medical societies across five continents, including the American College of Cardiology, the European Society of Cardiology, and the Japanese Circulation Society, to update their guidelines or scientific/consensus statements to recommend use of IPE for primary and secondary prevention of CVD events.

Areas covered: This review discusses the incorporation of IPE into international guidelines and scientific statements, noting areas of consensus and distinction. As background, this review also describes the CVD benefits and risks of IPE as a statin adjunct, and outlines current data regarding the potential mechanisms of CVD risk reduction by EPA (as IPE) beyond triglyceride reduction.

Expert opinion/commentary: IPE is unique among 'triglyceride-lowering' treatments in having strong CVD outcomes data and, therefore, a broad international consensus among professional medical society guidelines and statements endorsing its use for CVD risk reduction in patients generally meeting REDUCE-IT inclusion criteria. IPE should be considered for CVD prevention as a statin adjunct in all such patients.

Plain Language Summary: Cardiovascular disease (CVD) remains the leading cause of death worldwide. Statin monotherapy is conventionally used first-line to reduce the risk of CV events, such as heart attacks and strokes, in patients with elevated cholesterol. However, considerable risk remains despite appropriate control of cholesterol levels with a statin. Consequently, research has focused on treatment of additional therapeutic targets to reduce this remaining CV risk. One such target is elevated blood triglyceride levels. Unfortunately, most drugs that lower triglyceride levels, such as niacin, fibrates, and mixed omega-3 fatty acids, have not reduced the risk of cardiovascular events in clinical trials when added to statin therapy. However, the omega-3 fatty acid eicosapentaenoic acid ('EPA') administered in highly purified form as icosapent ethyl (IPE) has emerged as the first omega-3 fatty acid, and the first triglyceride-lowering agent to prevent CV events when added to statins. This was demonstrated most notably in the pivotal REDUCE-IT trial, in which IPE reduced the risk of major CV events by 25% in high-risk patients with mildly to moderately elevated triglyceride levels despite statin-controlled cholesterol levels. The mechanisms responsible for this reduction in CV events appear to go far beyond lowering triglyceride levels alone. In light of the positive results from the REDUCE-IT trial, IPE was approved for CV disease risk reduction globally, including in the United States, Canada, European Union, and the United Kingdom, and its use is being increasingly endorsed in United States and international statements and guidelines for managing CV risk. Despite minor differences among guidelines, there is strong consensus that IPE should be considered for use in CVD prevention in all patients who meet the proposed criteria.

Spain reimbursement decision soon? Position for new Regional Business Manager for Madrid posted yesterday. To oversee 8-10 sales reps.

Check out this job at Amarin Corporation: https://www.linkedin.com/jobs/view/3190928520

Similar position posted today for Seville, Andalusia region

Check out this job at Amarin Corporation: https://www.linkedin.com/jobs/view/3192817986

Recent Updates in Hypertriglyceridemia Management for Cardiovascular Disease Prevention

Published: 27 July 2022

https://link.springer.com/article/10.1007/s11883-022-01052-4

Good & fair summary of Omega-3s

“In sum, not all omega-3 FA are the same — the dose, type of preparation, and achieved EPA levels likely matter. No established benefit has been established for the dietary supplements of omega-3 FA, which should not be used for prevention. However, IPE can be considered for high risk patients with established ASCVD or diabetes plus additional risk factor who have residual TG elevation despite statin therapy.”

This was discussed in the past and pharmacist PharmacyDude noted it’s not a solution as generics don’t substitute based on brand name but rather chemical name, icosapent ethyl

NS, I have not been tracking API supply so I have no opinion on that.

dogn

Consider also letter to the WSJ editor:

https://www.wsj.com/articles/letter-to-the-editor-wsj-how-to-submit-wall-street-journal-guidelines-11647960749

Very nice note, North. Hope WSJ can fix their glaring omission.

dogn

The Icosapent Ethyl BRAVE-EPA Alzheimer’s trial is still ongoing.. completion Jan. 31, 2023:

https://www.clincosm.com/trial/alzheimers-disease-madison-icosapent-ethyl-ipe-gel-cap

https://clinicaltrials.gov/ct2/show/NCT02719327

Multimodality Imaging Trials Evaluating the Impact of Omega-3 Fatty Acids on Coronary Artery Plaque Characteristics and Burden

Published Online: June 30th 2022
Heart International. 2022;16(1):2–11
Authors: Venkat S Manubolu, Matthew J Budoff, Suvasini Lakshmanan

https://www.touchcardio.com/atherosclerosis/journal-articles/multimodality-imaging-trials-evaluating-the-impact-of-omega-3-fatty-acids-on-coronary-artery-plaque-characteristics-and-burden/

“As research into the optimal management of dyslipidaemia develops, there is a need for additional therapy beyond statins to reduce the risk of atherosclerotic CVD. In large cardiovascular outcome trials, EPA has demonstrated cardiovascular benefit.49,50 Furthermore, multiple serial-imaging studies have shown benefits of OM3FAs on plaque progression and characteristics. IPE especially has favourable efficacy and safety, and is superior to other OM3FAs in reducing cardiovascular risk. Future research should compare EPA with EPA + DHA to account for the contradictory outcomes observed in some of the outcome trials with EPA + DHA.52 Additionally, we must acknowledge that the pleiotropic effects of IPE may have contributed to the disparities between trials. Current research and accumulating evidence support IPE as an adjunct therapy to statins to reduce residual cardiovascular risk.”

From Expert Review of Cardiovascular Therapy

Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements

https://www.tandfonline.com/doi/full/10.1080/14779072.2022.2103541

This paper was funded by Amarin Pharma, Inc.

Areas Covered

This review discusses the incorporation of IPE into international guidelines and scientific statements, noting areas of consensus and distinction. As background, this review also describes the CVD benefits and risks of IPE as a statin adjunct, and outlines current data regarding the potential mechanisms of CVD risk reduction by EPA (as IPE) beyond triglyceride reduction.

Expert Opinion/Commentary

IPE is unique among “triglyceride-lowering” treatments in having strong CVD outcomes data and, therefore, a broad international consensus among professional medical society guidelines and statements endorsing its use for CVD risk reduction in patients generally meeting REDUCE-IT inclusion criteria. IPE should be considered for CVD prevention as a statin adjunct in all such patients.

HIGHLIGHTS

Icosapent ethyl (IPE) is approved for reducing persistent cardiovascular disease (CVD) risk in Canada, EU, US, UK, Hong Kong, and parts of the Middle East

IPE is widely recommended for CVD prevention by several leading US and non-US medical societies (in their guidelines and/or scientific statements)

These approvals and endorsements are based on strong evidence of CVD reduction with IPE in high-risk patients with mild to moderate triglyceride (TG) elevation despite control of low-density lipoprotein cholesterol (LDL-C) by statins

Most of these recommendations endorse IPE for patients with TG levels in the range studied in REDUCE-IT (1.5–5.6 mmol/L [135–499 mg/dL])

Most of these recommendations explicitly exclude other omega-3 products, which have not demonstrated CVD benefits in contemporary trials

Some guidelines recommend statin treatment sufficient to “control” LDL-C levels, whereas others recommend “maximally tolerated statin” therapy

The Japanese, the National Institute for Health and Care Excellence, and the US Department of Veterans Affairs/US Department of Defense guidelines recommend IPE use only for secondary prevention

The CVD risk reduction in REDUCE-IT appears unrelated to on-treatment TG levels, but instead may be due to anti-inflammatory, anti-oxidant, membrane-stabilizing, and/or endothelial function effects

IPE should be considered for use in CVD prevention in all patients meeting relevant guideline and/or regulatory criteria

https://www.newswire.ca/news-releases/hls-announces-that-vascepa-r-is-now-reimbursed-by-ontario-s-provincial-drug-plan-894499118.html

Deepak Bhatt presenting part of CME course at EBAC-accredited symposium at ESC Congress 2022

AGENDA - AUG. 26, 2022 - BARCELONA, SPAIN

https://pace-cme.org/2022/07/11/new-frontiers-in-ascvd-risk-reduction-integrating-icosapent-ethyl-in-clinical-practice/

Educational Objectives

Understand the key findings of large-scale omega-3 fatty acids clinical trials and how this information relates to reducing ASCVD events in clinical practice

Apply recent clinical trial evidence of icosapent ethyl on a case-by-case basis for patients with established CVD who are on statins and at risk of further CV events
Identify barriers to the implementation of effective, long-term management of ASCVD

Agenda

Introduction - Lina Badimon, MD - Barcelona, Spain
ASCVD & residual risk: recent clinical insights with icosapent ethyl? - Deepak Bhatt, MD – Boston, MA, USA
A continuum of multifactorial benefits of icosapent ethyl? - Magnus Bäck, MD, PhD – Stockholm, Sweden
Integrating icosapent ethyl in clinical practice: which patients will benefit? Subodh Verma, MD - Toronto, ON, Canada

4. Discussion
This study demonstrates that a substantial percentage of patients who have undergone CABG surgery at a tertiary Australian hospital may be eligible for icosapent ethyl therapy in the real-world setting, which is important as residual CV risk remains high in this cohort despite LDL-C lowering [8]. Although hypertriglyceridaemia can contribute to residual CV risk, the benefits of icosapent ethyl in the REDUCE-IT trial appear to be similar across baseline triglyceride levels [3]. The mechanisms by which icosapent ethyl reduces CV risk are likely multi-factorial and has been reviewed elsewhere [9].

Our data confirm the only other published real-world study with a similar research question, which utilised a Canadian database and demonstrated a similar estimate of 21.9% eligibility for icosapent ethyl in patients who have undergone CABG surgery [7]. The study also found that the percentage of statin-treated patients eligible for the therapy based on Health Canada and United States Food and Drug Administration (FDA) criteria were 33.6% and 26.4% respectively [7]. Given the high frequency of patients with coronary artery disease that are eligible for icosapent ethyl, and given that it is recommended by international guidelines, the addition of the medication to hospital formularies will have major implications [10]. The therapy has been shown to be cost-effective in the secondary prevention setting [11].

Awesome. Thanks, Laurent!
-dogn

Laurent,

For clarity and to avoid confusion I suggest adding in these posts summarizing your research “in placebo arm” when reporting a trial “annualized absolute” MACE rate. It would be great also to add what type of placebo was used.

Great research… thanks for sharing.
dogn

Inducing Infringement with the Skinny Label
July 17, 2022
Dennis Crouch

https://patentlyo.com/patent/2022/07/inducing-infringement-skinny.html

Eddingpharm-funded IPE safety and tolerability study in Chinese population published July 3 2022

Pharmacokinetics of Icosapent Ethyl: An Open-Label, Multiple Oral Dose, Parallel Design Study in Healthy Chinese Subjects
https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.1130

The majority of the EPA in plasma is bound to phospholipids, TGs, and cholesterol esters, with only 1% present as nonesterified fatty acids. More than 99% of nonesterified EPA is bound to plasma proteins.11, 12 EPA is not only found in plasma but is also widely distributed in red blood cells (RBCs) and other tissue types. The pharmacokinetic (PK) profile of EPA in healthy Western people is well known.13 The PK profile of oral omega-3 carboxylic acid 4 g—a mixture of the free fatty acid forms of EPA and docosahexaenoic acid—after single and multiple dosing in healthy Chinese subjects was consistent with that observed in other ethnic populations.14-16 However, there were no PK data of EPA in Chinese individuals after taking IPE capsules before the current study. The objective of this study was to evaluate the PK, safety, and tolerability of EPA after multiple doses of IPE in healthy Chinese subjects.

Healthy Chinese men or women 18 to 55 years of age with body mass index between 18 and 26 kg/m2 were enrolled in the study.

The study was divided into 3 parts: a 14-day screening period, a 28-day treatment period, and an 18-day posttreatment PK sampling period. Twenty-four eligible subjects were randomly divided into 2 groups of 6 males and 6 females in each group. Group A received IPE 2.0 g/day; group B received IPE 4.0 g/day. Subjects in both groups received IPE capsules orally with a meal in the morning and evening (twice daily) during days 1 through 27 and received only the morning dose (once daily) on day 28. At the study site, all meals were consumed within 30 minutes. Subjects were admitted to the study center on day –1 and discharged on day 31 after blood sampling. Similarly, they were confined for 1 overnight before blood sampling and safety assessments on days 33, 36, 41, and 46.

The results from this study were also compared to another pharmacokinetic study conducted with IPE 4 g/day and 2 g/day in a Western population.13 The result of plasma total EPA reaching steady state and RBC EPA not reaching steady state was consistent with the Western results at doses of 2.0 g/day (twice daily) and 4.0 g/day (twice daily). The median tmax of plasma total EPA, RBC EPA, and plasma unesterified EPA were 5 hours, 5 hours; 6 hours, 5 hours; and 3 hours, 5 hours vs 5 hours, 5 hours; 12 hours, 8 hours; and 5 hours, 5 hours in the Western population. Except for RBC EPA, the other 2 were consistent. The results of mean exposure to EPA, especially plasma total EPA, appeared to be dose-proportional and consist of 2 studies. These findings suggested that the PK of EPA in Chinese and Western subjects were comparable.

The results of safety evaluation indicators such as adverse events, clinical laboratory tests (blood routine, blood biochemistry, urine routine, coagulation function), vital signs, 12-lead ECG, and physical examination revealed that Chinese healthy subjects after receiving IPE capsules orally for 28 days in the dose range of 2.0 to 4.0 g/day were safe and tolerable.

Conflicts of Interest
Y.L. and H.L. are employees of Eddingpharm (Suzhou) Co Ltd. Other authors report no conflicts of interest in this work. The study was also registered on http://www.chinadrugtrials.org.cn (CTR20180597). Funds were used for medications and pharmacy administration, investigators, institutional review board fees, and statistical analysis. Editorial assistance was provided by Jin Yan, Eddingpharm (Suzhou) Co., Ltd.

Funding
This study was funded by Eddingpharm (Suzhou) Co., Ltd.

HDG… thanks for your lost sleep to produce this detailed, valuable analysis. Sorry if my morning post made you promise a same day post that kept you up very late! Appreciate it.

dogn

“ps.: I am working on a full (long) explanation / details ... will be posted later 2day”

Thanks HDG - Looking forward to seeing your post.

dogn

Some portion of declining revenue in last quarter was due to decreased wholesaler inventory while at same time Amarin inventory increased ~$55M.

https://investor.amarincorp.com/node/21876/html

From 10-Q p.32: “Further, while still remaining within normal industry ranges, the wholesalers decreased their branded VASCEPA inventory levels as of March 31, 2022 by 40% in terms of bottles from the beginning of the quarter. By comparison, wholesaler inventory balances decreased by 10% during the first quarter of 2021. The inventory balances for the first quarter of 2022, as calculated based on days of sales on hand, were near the high-end of the range at the beginning of the quarter and reduced to the low-end of the range at the end of the first quarter of 2022 compared to a slight increase at the end of the first quarter of 2021 compared to the beginning of the first quarter of 2021.”

Amarin’s revenues are booked at time of sales to wholesalers.
P.31 “Product revenue, net. All of our product revenue is derived from product sales of 1-gram and 0.5-gram size capsules of VASCEPA, net of allowances, discounts, incentives, rebates, chargebacks and returns. In the United States, we sell product to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, our distributors or our customers, most of whom resell the product to retail pharmacies for purposes of their reselling the product to fill patient prescriptions. Revenues from product sales are recognized when the customer obtains control of our product, which occurs at a point in time, typically upon delivery to the customer. Timing of shipments to wholesalers, as used for revenue recognition, and timing of prescriptions as estimated by third-party sources such as Symphony Health and IQVIA may differ from period to period.”

While RX have deceased, IMO revenue may positively surprise relative to 1st Q if wholesaler purchases increase to restock their inventory.

dogn

Kiwi,
Various fair value estimations may indeed be WAGS without knowing what goes into them, but point is there are a collection of these out there showing optimistic projections that shouldn't be "discounted" for their help in confirming we're far underwater.

As to MITIGATE, I notice that at the trial site https://clinicaltrials.gov/ct2/show/NCT04505098
when click to see definition of Estimated Primary Completion Date : February 28, 2022 it shows:

Here's another DCF estimate:
https://valueinvesting.io/AMRN/valuation/intrinsic-value
Intrinsic Value $3.74/share

Another current valuation indicator is comparison of current Price/Sales and Price/Book ratios to both AMRN 3-YR averages and those of market indices:
From https://marketchameleon.com/Overview/AMRN/Fair-Value-Price/
(+5-Yr averages from Morningstar link below)

AMRN vs. SPY Historical Price/Sales Ratio & Premium/Discount
AMRN Current Price/Sales 1.0 vs. 3-Yr Avg 6.3 vs. 5-Yr Avg 8.99
SPY Current Price/Sales 2.4 vs. 3-Yr Avg 2.7
AMRN -57% Discount relative to SPY

AMRN vs. SPY Historical Price/Book Value Ratio Premium/Discount
AMRN Current Price/Book 0.8 vs. 3-Yr Avg 4.2 vs. 5-Yr Avg 13.95
SPY Current Price/Book 11.7 vs. 3-Yr Avg 12.9
AMRN -93% Discount relative to SPY

From https://www.morningstar.com/stocks/xnas/amrn/valuation, "Index" (assume but can't confirm they mean the Biotech index) has current Price/Sales of 2.22 and Price/Book of 3.32 (and Price/Earnings of 17.79, Price/Cash Flow of 14.05).

As they say, garbage in, garbage out when it comes to modeling. It's impossible to know to what extent any of these models include pending EU and ROW sales expansion, recent changes in exclusivity in formularies, let alone impact of Healthnet lawsuit or combo pill on regaining US Market.

Found this online "Biotech Valuation Calculator" allowing anyone to use their own inputs to crunch numbers:
https://bioboyscout.com/amrn/

Have also been adding shares at these levels. GLTA

dogn

Denner used DCF modeling to conclude AMRN was significantly undervalued when establishing Sarissa Capital's ~6% stake, with cost basis ~$4.46
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167621357

Apart from possible hedging profits, they're down ~71% at today's $1.29 close.

I trust they have confidence in their numbers to invest $107M and hold while current stake valuation now ~$31M. Would like to know their calculated true value estimate.

Your $3B~$7.56/share.

Some other DCF valuations, FWIW:
https://www.alphaspread.com/security/nasdaq/amrn/dcf-valuation/base-case
Base Case $3.29 per share ($1.31B market cap; undervalued by 59%)
https://www.alphaspread.com/security/nasdaq/amrn/dcf-valuation/bull-case
Bull Case $12.26 per share ($4.87B market cap; undervalued by 89%)

https://www.macroaxis.com/valuation/AMRN/Amarin-Corp-ADR
"Prevailing Real Value" of $3.45 per share ($1.37B market cap; undervalued by 63%); Estimated Upside to $11.81 ($4.69B market cap; undervalued by 89%)

https://simplywall.st/stocks/us/pharmaceuticals-biotech/nasdaq-amrn/amarin
"Trading at 88.6% below our estimate of its fair value" (based on yesterday's $1.35 close), implies $11.84 per share fair value ($4.7B market cap)

Current average analyst 12 month target price $3.57 ($1.42B market cap).
https://www.marketwatch.com/investing/stock/amrn/analystestimates?mod=mw_quote_tab

Greater certainty with projections will come with MITIGATE & RESPECT-EPA results, additional country approvals/reimbursement data, combo pill, with wildcards like BRAVE Alzheimers trial. Going to be a long slog, but I'm optimistic for long term investment success. Latest MO noise completely disregards JELIS/CHERRY/EVAPORATE non-MO placebo trial successes, clear anti-inflammatory action of EPA, that biomarker changes were small on absolute level, etc. Sure seems AF/MH STAT team has an agenda to so persistently attack. Very one-sided story IMO. Would like to see their conflict of interest disclosures.
dogn

Waiting for the red flags to come out

Wondering if 425K is derived from number currently taking statins, or number eligible to take statins. Or otherwise estimated. If it’s the number already taking statins, could easily capture >10% IMO as they’re already compliant and thus proactively concerned about their health and likely willing to embrace adding Vascepa for proven further RRR benefit. Guess that this 425K is based on analysis of those currently fitting description:

“The just-published final technology appraisal document recommends that Vazkepa (icosapent ethyl) can be prescribed to people in England and Wales for adult patients with high-risk cardiovascular disease and elevated levels of triglycerides (1.7 mmol/litre or above) in their blood who are already taking statins.”

Haven’t researched details of this 425K, but suspect Vascepa can exceed 10% (will take time and depend on physician education, and maybe not happen GIA but I assume BP watching believe they can achieve better).
dogn

NICE unlocks use of Amarin’s Vazkepa in 425k NHS patients
July 15, 2022
Health technology assessment (HTA) agency NICE has finalised its guidance on Amarin’s Vazkepa, clearing the path for GPs to start prescribing the drug in up to 425,000 NHS patients at high cardiovascular risk because of raised triglyceride levels.
https://pharmaphorum.com/news/nice-unlocks-use-of-amarins-vazkepa-in-425k-nhs-patients/

The just-published final technology appraisal document recommends that Vazkepa (icosapent ethyl) can be prescribed to people in England and Wales for adult patients with high-risk cardiovascular disease and elevated levels of triglycerides (1.7 mmol/litre or above) in their blood who are already taking statins.

That includes people who have suffered a prior stroke or heart attack, or who have other conditions like unstable angina or peripheral artery disease. They should also have LDL-cholesterol (LDL-C) levels above 1.04 mmol/litre and below or equal to 2.60 mmol/litre.

All local NHS formularies in England and Wales will now need to make Vazkepa available within 90 and 60 days, respectively.

NICE notes that there are currently no treatment options to reduce the risk of cardiovascular events in people taking statins who have controlled levels of LDL-C but raised levels of triglycerides.

Vazkepa is a highly purified omega-3 fatty acid formulation that was approved for this indication by the Medicines and Healthcare products Regulatory Agency (MHRA) last year.

In the REDUCE-IT study, which enrolled 8,179 statin-treated adult patients with moderately elevated triglyceride levels who were followed for a median duration of 4.9 years, Vazkepa hit its objectives with a 25% relative risk reduction and a 4.8% absolute risk reduction in the first occurrence of major adverse cardiovascular events (MACE) versus placebo.

The drug has also been approved for primary prevention of MACE in people with diabetes and cardiovascular risk factors, but NICE said the data suggest that Vazkepa is “unlikely to be cost effective for primary prevention” so is not recommended for these patients.

Vazkepa is taken as two tablets twice daily, and has a list price of £144.21 per pack of 120 capsules, although NICE notes that its cost “may vary in different settings because of negotiated procurement discounts.”

NHS England has estimated that between 25% and 35% of people having statin therapy have elevated triglycerides.

Amarin first introduced its drug in the US as Vascepa in 2012, but only made it available in Europe last year, starting with a German launch last September. It plans to launch the product in up to six European countries this year.

Vascepa has started to face generic competition in the US, and saw its first-quarter revenues – which come almost entirely from Vascepa – fall to $95 million from $142 million in the same period of 2021.

“We have a once in a generation opportunity to transform the lives of cardiovascular patients across Europe, and today’s announcement regarding NICE’s final guidance will help us realise that mission in one of our key markets,” said Laurent Abuaf, head of Amarin Europe.

“Following the successful completion of the HTA assessment in the UK, and the positive reimbursement guidance, our local teams in every country in Europe will be inspired by how the UK will be prioritising access to local health economies.”

I thought you were posting like wildfire today because you knew you had unlimited free posts during iHub Happy Hour 4-5 pm

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