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Chinese exclusivity timelines are very short vs US and EU. Especially for a drug not 1st developed in China like V where there's an actual penalty to exclusivity. I had a post about that on here a while ago. Clock is already ticking on it since the product is on the market there. Mochida and Meiji could be timing that.
Kiwi, No.
Sleven,
Exclusivity ? Epadel is not chemically the same as Vascepa . Vascepa is DEVOID of DHA where as Epadel has 2-10% DHA . One of the reasons AMRN was able to patent Vascepa .
Mochida isn't trying to sell their exact version of Vascepa .
Kiwi
Whala, Always guessing - guessing - and then guissing again on top of your latest spin !!
And always - ALWAYS - with the optimal negative angle for future of Amarin !!
---------------------------------
You could be Nissen - as several posters have suggested !!
Kiwi, This is silly conversation. I'm not sure if Mochida can even apply for an approval. Amarin has an exclusivity period.
Sleven,
It does in China . China will restrict access until Mochida comes up with the lowest price they can make money on ...in exchange for as you say ...access to a " vast " market .
Its buying market access
Kiwi
Kiwi, Opening a new market, and launching a generic, makes no sense.
Sleven,
Kiwi, No. When I have more time I will list their suppliers.
Sleven,
Yes but the problem is many of the things you say are years away. I thought Germany approval would not even come for at least another year minimum if it actually gets approved. We are looking at 2026 at the very earliest for Europe revenue to probably be any good. So a sale maybe by 2027 at the earliest which is kind of depressing given this has been nothing but dead money for years now. The buyback offers a small glimmer of hope but who knows when that will get approved.
My guess is that its the cheapest way for them to enter the Chinese market .
The raw material ( API ) has to come from somewhere . The Chinese can't just create it in a lab somewhere .
You follow this more then I but isn't Mochida a large supplier of API ?
Kiwi
Kiwi, Why would Mochida de selling a generic version of their product?
Sleven,
Kiwi, If Amarin was selling the product, I would agree.
Sleven,
N7. Do you know anyone with personal experience who has done business in China or even with business people in Hong Kong ?
If you did they IMHO would tell you your view is naive .
If you think the generics have stolen the market from AMRN in the US ...thats are warm up for what you'll see in China .
Kiwi
I just looked her up. She's now Sr. Clinical Scientist at Merck. i'll try to reach out to her.
https://www.linkedin.com/in/angie-torres-adorno/
Nice find. Perhaps we should contact the author about a follow up and if her employer (MD Anderson, Cancer Center) is interested in performing an RCT.
interesting study on EPA and breast cancer in 2018, published in oncogene...never followed up with clinical studies
Eicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux
Angie M. Torres-Adorno,1,2 Heidi Vitrac,3 Yuan Qi,4 Lin Tan,5 Kandice R. Levental,6 Yang-Yi Fan,7 Peiying Yang,5 Robert S. Chapkin,7 Bedrich L. Eckhardt,2,* and Naoto T. Ueno2,*
The publisher's final edited version of this article is available at Oncogene
Abstract
Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, currently lacks effective targeted therapy options. Eicosapentaenoic acid (EPA), an omega-3 fatty acid and constituent of fish oil, is a common supplement with anti-inflammatory properties. Although it is not a mainstream treatment, several preclinical studies have demonstrated that EPA exerts anti-tumor activity in breast cancer. However, against solid tumors, EPA as a monotherapy is clinically ineffective; thus, we sought to develop a novel targeted drug combination to bolster its therapeutic action against TNBC. Using a high-throughput functional siRNA screen, we identified Ephrin type-A receptor 2 (EPHA2), an oncogenic cell-surface receptor tyrosine kinase, as a therapeutic target that sensitizes TNBC cells to EPA. EPHA2 expression was uniquely elevated in TNBC cell lines and patient tumors. In independent functional expression studies in TNBC models, EPHA2 gene-silencing combined with EPA significantly reduced cell growth and enhanced apoptosis compared with monotherapies, both in vitro and in vivo. EPHA2 specific inhibitors similarly enhanced the therapeutic action of EPA. Finally, we identified that therapy-mediated apoptosis was attributed to a lethal increase in cancer cell membrane polarity due to ABCA1 inhibition and subsequent dysregulation of cholesterol homeostasis. This study provides new molecular and pre-clinical evidence to support a clinical evaluation of EPA combined with EPHA2 inhibition in patients with TNBC.
Triple-negative breast cancer (TNBC) is an aggressive disease that comprises 10–20% of all breast cancers. It is a heterogeneous disease that is often characterized by its strong metastatic potential and poor prognosis compared to estrogen receptor (ER)/progesterone receptor (PgR)-positive and HER2-positive breast cancers 1. While conventional chemotherapy is effective in the short term, TNBC often becomes refractory, and the lack of targeted therapy hampers a clinical solution for this disease 2.
Inflammation, a biological process designed to fight infections and heal wounds, can inadvertently support tumor formation and growth by supplying bioactive molecules that facilitate tumor progression and metastasis 3. Pathological assessment of TNBC has identified increased expression of molecular mediators of inflammation, such as prostaglandin G/H synthase 2 (COX2), and prostaglandin E2 (PGE2), representing potential therapeutic targets 4. Recent finding by our laboratory have observed that inhibition of inflammatory pathways through administration of celecoxib (a COX2 inhibitor) 5, or as observed by other using Lovaza (a highly purified, prescription-strength form of the omega-3 acid ethyl esters [O3AEE]: docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) 6, can impair the growth of TNBC cells in vitro. Supporting our results, omega-3 fatty acid supplementation has been shown to reduce the growth of rat sarcoma tumors and DMBA-induced mammary tumors in vivo 7–9. Collectively, these studies suggest that the anti-inflammatory action of O3AEE have therapeutic potential. However, the translation of these compounds has been hindered by: 1) inconsistencies in sources, routes of administration and O3AEE composition 9, 2) absence of an established biomarker for therapeutic action, and 3) no definitive subpopulation of breast cancer patients that would benefit from therapy. As a result, there is a critical and unmet need to develop a rational, targeted-approach for the clinical testing of O3AEE in TNBC.
Towards greater clarity regarding the use of O3AEE as a therapeutic, we sought to investigate the anti-tumor effect of highly purified EPA (Vascepa, icosapent ethyl; Amarin Pharma Inc), which was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of hypertriglyceridemia 10. We demonstrate that EPA has potent tumor suppressive activity in preclinical models of TNBC. However, with no established therapeutic role for EPA in the TNBC patient population, translation of an EPA-based therapy through combination with conventional cancer therapy requires justification.
The main goal of this study was to identify a molecular target that could be targeted in combination with EPA for the effective clinical treatment of TNBC. To this end, we detail a functional genomics-based screen that identified the receptor tyrosine kinase EPHA2 as a therapeutically druggable target that enhances EPA-based therapy in TNBC, and present relevant preclinical studies that ESTABLISH THE RATIONAL FOR A PHASE 1 CLINICAL TRIAL the rationale for patients with TNBC....(however, phase 1 testing has never been done, to my knowledge)
Results
EPA inhibits the growth of TNBC tumor xenografts
While O3AEE demonstrate anti-tumor effects 8, EPA as a monotherapy in TNBC has not yet been tested. Thus, we initially assessed the anti-tumorigenic potential of EPA in a preclinical xenograft tumor model of TNBC (SUM149PT). EPA therapy was well tolerated at both 0.4 g/kg and 0.8 g/kg doses (equivalent to the human FDA-approved EPA dose; Supplementary Figure S1), with no change in body weight noted (data not shown). EPA levels were readily detectable in the sera obtained from mice undergoing therapy (Figure 1A) and, importantly, were significantly elevated in the cell membrane (phospholipid) fraction of TNBC tumor xenografts (Figure 1B). EPA therapy dose-dependently inhibited the growth of SUM149PT xenografts (Figure 1C), which led to a significant extension in survival (designated as the time required to obtain a 1 500 mm3 tumor) (Figure 1D). These data suggest that EPA is THERAPEUTICALLY ACTIVE active in VIVO and can reduce the growth of aggressive TNBC xenografts.
CBB, I tend to think it does not work like that. First, I'm not sure Bayer or anyone else has a much better shot at working with the German government than Amarin. And to be honest, I think the issue is more of an economic/budgetary issue in Germany. Plus, I don't think any "gravitas" would extend over to Italy and France. It's just too much risk for a BP right now. Too many unsettled questions. I think once we get something done with these three countries (and by that time, the litigation may be more in focus), then Denner would likely start shopping the company. BP's just don't like risk, and they don't like uncertain revenue. And unfortunately, Amarin has given them a lot of both the past 4 years. Right now, time is our ally.
DAR, I don't know if institutional ownership percentage matters. I follow the quarterly activity report in order to monitor sentiment. I assume they have research staff with some skill.
As far as the lawsuit goes, I believe the judges expressed their opinions with a degree of clarity. I think we are going to see a remand. We need to wait for the order. Section 8 carve outs are the target of the suit. Hikma is the easiest target. Advertising for HTG instead of SHTG was a major blunder. The wording in the order could open up other generic companies to litigation. In the arguments, the chief judge said that generic companies should be required to make clear, what their product is generic for. At the moment that is not part of the law.
Sleven,
MK, I'm not concerned about competition from Mochida. The Chinese market is enormous. Vascepa should receive a CVD indication, that Epadol probably won't get. That will effect reimbursement.
Sleven,
Thanks for that link. What is a good number for % of institutional ownership that we need to see? Is 50% a good number or do we need it higher? We do need a catalyst to drive confidence in the market and hopefully we begin to see that soon with the Cantor presentation next week and the impending buyback.
A positive response back from the judges from the Hikma proceedings should instill some fear in Hikma, DRL and other generics to back out of sellling GV in the states. I know that is a long shot but it is a possibility.
Thanks for all your contributions to this board.
wow! 21% institutional holdings. I figured we were in the low 30's- looking rather moribund at the moment. Looks like Denner's original investment is more than all current institutional value.
Thank NS. Your research is invaluable! My concern is if Epadel delivery of EPA is more effective then AMRN's and we don't have a partnership with Mochida it will really hurt AMRN.
JRoon71, What I would like to know is this. Are there any Eurocentric BP that believe they
could get Vazkepa reimbursements from Germany, Italy, & France. For example, if Bayer
owned AMRN would they have the gravitas to get reimbursements for Germany? If so, why
wouldn't one of these make their move? Then there is the question of Vazkepa being studied
as an adjunct drug for use with any other cancer therapy and/or drug. Would not a BP like Merck
which has Keytruda want to do some trials with Vazkepa? My hope is that Denner is working
on this.
John...After the FDA approved Vascepa for the CVD indication, J.T. was not interested in selling Amarin...This was based on JT's expectations that Vascepa would become a blockbuster drug, globally...Post the Judge Du debacle, selling came more into focus....After J.T.'s departure, and with Amarin now in the hands of new management, selling the company became an even better strategy...since Amarin now realized that it would lack sufficient assets to achieve it's original goal of worldwide sales.
Jim re your comment ,
MK,
https://clinicaltrials.gov/study/NCT04239950?term=Vascepa&page=2&rank=12
This is the study that is being conducted in China. It looks like Mochida is interested in selling Epadol in China. Both Amarin and Mochida have their own partners in China.
Sleven,
I am confused, is Mochida a Partner with AMRN in China or is this Epadel formula separate from AMRN? Would appreciate anyone who can clarify, please. Thx.
Whal, I thought the original indication for Mevacor was for secondary prevention. I believe the West of Scotland study with Pravastatin was what gave way for the primary prevention indication. Lipitor, in my opinion has the worst SE profile. Rosuvastatin (Crestor) would be my choice. With an LDL of 160 (thanks mom) I began taking a statin. I had trouble with Lipitor and then moved to Pravachol. In the end, I quit altogether, feeling somewhat protected with an HDL of 70 (thanks mom). Mom's LDL was in the 160 range also, but with an HDL of 120! She's 92 now). Strangely (not really, I was drinking nothing but filtered water, using table salt, had a whole house water filter, not. getting minerals), in my mid 40's I developed proximal afib, then eventually permanent afib. While researching a cure, I found a liquid form of magnesium, I believe they refer to it as pico ionic. Anyway, I took the BID dosed magnesium, regardless of taste. It did not alleviate the Afib, so I went in for ablation. That was 7 years ago and no reoccurrence, which is typically 50%. With 70% of the country having magnesium deficiency, I continue to take a QD dose. But here's the kicker! After a few months, I went in for a Wellcheck. My LDL dropped from 160 to 129, no meds. Still there today. Back pain (which I'd struggled with for years, despite exercising/stretching 5 days/wk) is absolutely gone. Muscle strength, lung capacity too were much improved. Astounded, I read up on what exactly Mg does. Runs over 70 or so enzymatic processes in the body. It appears it is literally a natural (HMG-CoA) reductase inhibitor, but also huge for muscle repair and function, etc., etc. Read up on Magnesium, it's amazing. Lastly, even though your blood work will show normal Mg levels, you could be and probably are deficient. Why? The test just measures systemically, what's in the blood. Our organs, muscles, when deficient rely on our blood to rob from the areas of abundance, distributing the areas of need. The blood will show normal, even thought the heart, major muscle groups are deficient. I asked my CD "why the test if it isn't a true measure?" He said it just part of the panel. WTF. There is a legitimate test for Magnesium, but you'll end up paying for it. Corrupt medicine. Also figured out docs don't work through using Magnesium on patients. Too difficult, tastes bad, uncomfortable side effects in the beginning.....but the body adjusts! Good luck, you have to do your own research to make informed decisions WITH your MD regarding your health, because they'll do the quickest and easiest treatment.
Caddie ...After approval of the Marine indication mid 2012 the Ceo at the time floated 3 options ...sell the co , partner with a BP or GIA ( go it alone ) .
12 weeks went by as the Ceo ( Z ) explored these options and when no buyer or partner emerged they announced GIA and the stock tanked.
Kiwi
There were BO rumors in October of ‘12 (that’s when I first bought in) and it went from $11 to $14 but was “Z” really trying to sell 12 years ago? How does anyone really know or verify M&A until it actually happens
zip…again, why no credible offer (credible offer would have to be taken to shareholders and disclosed) in 10 years…..Z was trying to sell, his successor was open to offer, the prior Board was motivated to sell during proxy contest (to save embarrassment of getting voted out)…not even credible low ball offer……why?
RMB, I believe Meiji Seika Pharma has the marketing rights for Epadel in China. That was announced in April.
Not sure about approvals and reimbursement yet.
RMB, Mochida was apparently required to conduct a clinical trial in China. Same as Amarin. That trial has not been updated for some time. I haven't seen any information about a commercial launch.
Sleven,
Sleven, I did dig up that link as well showing the start of clinical trials. But no info about results or if it is being reimbursed in China. This is what Tats posted:
https://pj.jiho.jp/article/250727
I guess to Kiwi's point, the Generics don't have a CVD indication here in the States but are still getting a bunch of sales.
It's China ...it doesn't matter . They will rip it off anyway
Kiwi
Kiwi, No CVD indication.
Sleven,
Yep and it'll be a lot less expensive than Vascepa .
Meanwhile we await Denner/ Holts grand plan for cracking the remaining big 3 EU market ...where they at least have patent protection .
Kiwi
JRoon, Zip, a question about China. A couple of days ago I believe Tats posted a link that described where Epadel was going to be marketed in China. There was a paywall and I also could not find more info about it elsewhere. My question is whether Epadel already has reimbursement, or is just an over the counter there? Would it be competition for V?
zip, I hope the Denner, Holt team - makes themself visible (knocks the door) at Novo Nordisk - the European Pharma Company that is absolutely flying for the moment.
Some poster here - a few weeks back argued brilliantly 'why Amarin CDV fighting drug Vascepa / Vazkepa' - will fit perfectly into an area were NOVO right now can improve in their sortiment of successful drugs 🙂
Great points, Zip.
I think these are the most critical for a buyer:
No worries, Jasbg. I appreciate the post.
Thanks Sleven. I've used that site before (I think when snooping around for MITIGATE results), and one thing I noticed is that some trials still miss their reporting deadlines. But assuming all is well with the study, it seems that they should be reporting prior to CTAD.
Amarin is definitely for sale...some of the reasons the sale is being delayed are...
-The current price tag is presently too high
-Potential buyers are waiting to see more European approvals for the sale of Vascepa
-Buyers want to know about what European National Health Services will be willing to pay for Vascepa
-The same holds true for China
-Buyers want to see increased revenues before they agree to the prices being asked, which are far above the present market price
-Buyers are still awaiting more good news about other potential new indications for Vascepa
IMO the sale will occur...It's not if, but when!
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