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Millions of people, year after year, waste their money by buying fish oil, in the mistaken idea that it reduces CVD...Vascepa's only hope to avoid this confusion was to advertise to the public and to Docs that Vascepa is purified EPA from fish oil, but is NOT the same as fish oil...and Vascepa ACTUALLY DOES reduce CVD.
Amarin was sucker punched by judge Du who caused Amarin to lose the revenues that it needed to get this message out...Now That job will have to go to a BP that buys Amarin.
Kiwi...DME Rx has mainly been done by retina specialists due to potentially serious complications from serial intra-ocular injections of anti-VEGF meds...oral Rx for DME would present a landmark improvement in the Rx of DME... if it is proven successful.
DMC...Thank you for posting on these studies on IPE
One study, you linked ,especially caught my interest...It showed the beneficial effects that Icosapent ethyl can have on cardiovascular outcomes in cigarette smokers...Smoking and CVD's is a world wide problem,which can be ameliorated with IPE...
"In REDUCE-IT, IPE treatment was associated with a reduced risk of CV events in current and former smokers to levels observed in never smokers. While smoking cessation should always be recommended, these data raise the possibility that IPE treatment may attenuate CV hazards attributable to smoking"
Its difficult for Amarin to sue individual Docs for patent infringement...but pharmacy chains and pharmacy benefit managers(PBM's) and insurance companies are not immune from infringement suits.
Nuke...Docs hate wasting time, writing Rx's...Perhaps it would be a worthwhile trial for Amarin to distribute free Rx pads to Docs...inscribed, among the writings..."Vasepa 1 gram Q.I.D. P.O....along with the letters DAW".
Pharmacies would still ignore the Rx pads' DAW in some cases, but not in all.
At the very least, it would provide Docs with some inexpensive exposure to Vascepa, even if many Docs eventually throw the Rx pads away, as many of them would.
Capt....Nice U.K. growth in Vascepa usage....What stood out for me in your charts is that there were 185 MILLION Lipitor doses and only 189 THOUSAND doses of Vaskepa
Since most of the patients presently on Lipitor would be able to benefit by being on Vascepa, in addition to a statin...these figures point out the potential for outstanding growth in future Vaskepa sales volumes in the U.K.!
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.
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.
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!
Capt...The study on cervical cancer indicates..."a high level of plasma EPA was independently correlated with an increased incidence of CR(i.e.complete response after CCRT(i.e.concurrent chemoradiotherapy (odds ratio (OR), 0.980; 95% CI(i.e.confidence interval), 0.962-0.999, P=0.038). With a median follow-up of 41.3 months.
For us non GYN docs, who may be puzzled by the abbreviations in this important article ...The complete response is AMAZING and further emphasizes the fact that many cancer patients need EPA as a part of their treatment.
Tats...Let's refrain from making unnecessary, unproductive comments about Denner's personal life.
Amarin has the patent on its superior encapsulation, which affords better lab and clinical results than the encapsulation that generics are using.
This introduces the question of whether generic V is really "biosimilar" to Vascepa!...It is something that Amarin or a BP that acquires should explore.
If PFE were the potential prospective buyer, there would be no reason for HLS to end its Vascepa partnership with Amarin...It would need to be another BP that has expressed significant interest in buying Amarin.
Of course, we retail shareholders would be last to know.
J.T. had intentions of making Amarin into a BP by using Vascepa revenues to develop new indications for EPA meds and to acquire additional meds...Now Denner has intentions of selling Amarin to a BP with more assets
In retrospect, I believe that Amarin could actually have become a BP if everything hadn't came crashing down, due to the judge DU decision and the lack of U.S. courts' enforcement of infringement laws...I hope that Denner is more successful than J.T. was and I look forward to holding shares in the fortunate acquiring BP.
Here is a summary of Amarin's patents on LR-EtEPA
Abstract of patents WO2023146984
"Lymph-releasing compositions of fatty acids and uses thereof for lymphatic incorporation and systemic disease treatment
Abstract
Provided are compositions comprising one or more polyunsaturated fatty acids or derivatives thereof, a source of phospholipid, and optionally one or more additional emulsifiers, as well as methods of using the same to treat various diseases. In some embodiments, provided is a lymph-releasing composition of eicosapentaenoic acid ethyl ester (LR-EtEPA) and methods of using the same to increase EPA uptake in tissues and to treat various diseases including cardiopulmonary diseases, renal diseases, neurological diseases, and CANCER."
EPA is a med that needs development ASAP, not only for the CVD indication, but also for several other indications...If Amarin is unable to perform this task, Amarin should be sold to a BP that has the necessary assets to do it.
I am still awaiting more news from Amarin, fleshing out any new developments in the patenting of LR-Et-EPA or any future plans to market it.
Lymphoma is an all too common, potentially deadly cancer...and this disease could benefit from a treatment with an EPA drug... LR-Et-EPA could be a safe and relatively inexpensive treatment for Lymphoma...along with current treatments...such as Chemo, Antibody drug conjugates and Car-T therapies, which are all not only very toxic, but also very expensive.
IMO the BP that acquires Amarin..will have Vascepa PLUS new EPA meds and new indications to pursue and the time to pursue them.
Jasbg...Thank you for this self aggrandizing video of Nissen...My main take away from it is...that he thinks that badly needing a shave makes him look more like a medical expert.
ramfan...from the C.C...."we are genuinely ready to pivot to an authorized generic strategy and plans should we need to. And that's really simply a matter of us doing that with the partner we have selected."...... guesses as to the partner is?"
My guess is that CVS could supply enough shelves for Amarin to adequately display Generic Vascepa...
Amarin does not need a partner to produce their product, but only to display it for public consumption...if the patient still prefers prescription Vascepa, CVS can fill that request also....(although I assume they would be the same product, possibly with a different name...such as ecosapentethyl and perhaps a different price.
JR..."I would like to see Sarissa buy more shares alongside the buyback (or before it)"....I agree
If Denner's purpose for Sarrissa buying back shares is to to increase its share price, as we must assume it is....then it makes sense for him to be buying Amarin shares NOW or in the near future at these ridiculously low bargain basement prices.
Even Denner's additional purchases will give more credence to the success of Amarin for the future.
The market is NOT taking kindly to the C.C. and that is NOT unexpected...No news on any plans for LR-Et-EPA or comments on the relationship with Mochida...No news on the potential time line for mainland China approval of Vascepa for the CVD indication....
The market is unimpressed with the Amarin $50 million buy back, which we all knew about previously anyway....Amarin price is down over 10% as of the time of this post
Come on Amarin...How about a C.C. or a PR with some REALLY good news!...instead of sad news, which we already knew about.
-pfizer-genmab-cervical-cancer-therapy-wins-full-fda-approval
https://seekingalpha.com/news/4096045-pfizer-genmab-cervical-cancer-therapy-wins-full-fda-approval
I was seated next to my daughter, who lives in D.C. and who was at the meeting, sitting beside me...When we heard the 16 to 0 verdict of the FDA, IN FAVOR of Vascepa, we embraced.
I flew to Washington in 2019,at my expense, to attend the FDA hearing, which lead to the FDA approval of Vascepa for CVD... During the meeting, I noted what seemed to me to be an unusual conservatism on the part of the FDA...possibly because Vascepa was a med, which the FDA apparently realized, had the potential for very wide use and which had not been that widely used, up until that time.
I think that is why the FDA insisted on Vascepa having an indication for patients, who have 150 mgs/dcl. or more...They also suggested that Vascepa have on its label...a "black box warning" due to potential side effects..Thankfully, this idea was dropped by the participants at the FDA meeting and they did not require the label to mention it.
Now that Vascepa has been used by millions of patients, we have greater knowledge of its superior efficacy and its placebo like side effects....so the 150 mgms/dcl. of TG imperative is not as necessary as it was in 2019.
My own TG has been in the range of 50mgs/dcl I and was eventually able to convince my cardiologist to prescribe Vascepa for me.
CAPT... When the FDA, in 2019, approved Vascepa for treating patients for the CVD indication, the approval, at that time, was....ONLY for patients with TG's of 150 mgs/dcl or more...(plus diabetes or other risk factors for CVD).
Amarin now needs to contact the FDA about this NEW information, published after 2019, and petition for a NEW LABEL hearing, which reflects the new information, published after that time...and, for the FDA,to issue their updated approval for Vascepa for the treatment of CVD patients....which does NOT have the over 150 mgms/dcl TG criterion, previously mandated in their decision five years ago.
The Generics mandate for over 500 mgms/dcl of TG for THEIR indication can stay
A simple, but critical question for Holt to answer at the upcoming 5/1/24 C.C....Is Amarin (or a successor Pharma Co. which buys Amarin) committed or NOT committed,by the Amarin 2018 collaboration agreement with Mochida...to pay milestone or royalty fees to Mochida for its patented product, LR-Et-EPA sales in the U.S. or in Europe?
IMHO everything else that Holt discusses at this conference pales in importance as compared with this question...Unless some unexpected bombshell announcement is released.
Tal..." Holt’s narrative is the BOD’s focus on immediate, short-term, execution. To put it in his words: “the focus in the immediate term is really on executing what we have in our hands.”
i.e. In plain English Holt seems to be saying...Do what we can now to get the stock price up..and the sell the company and let the buyer take over and do the rest...e.g. developing LR-Et-EPA...This seems like a risk averse strategy that I'm not sure I'm happy with...Its a little disappointing...It isn't why I got into Amarin over 14 years ago
I could have bought Pfizer instead and benefited from a nice dividend all these years.
Tal Shu...I re-read your post #423521 and I will be interested in seeing what Amarin is able to divulge, affording clarity on some of the issues raised in your post...at the C.C. on 5/1/24.
MA5..."Fenofibrate is available in several formulations and is sold under several brand names, including: Tricor by AbbVie. Lipofen by Kowa Pharmaceuticals America Inc. Lofibra by Teva."...The FDA needs to replace these products with meds that are proven effective at reducing CVD.
Thank you for that most informative post.
I agree...judges, especially younger ones, like many human beings, have their eye on the next potential step in their careers...They don't want to make a misstep, that might mitigate against them in the future....This includes possible advancement to a higher position within the court or even to a higher court.
Even on the Supreme Court, it is not unheard of, to have a justice entertain still higher ambitions.
Tats Mochida agreed, in 2018, to COLLABORATE in the devlopment of new and better EPA meds
Amarin and Mochida Announce Collaboration on Future Development of EPA-based Drug Products and Indications...
June 12, 2018 05:00 ET | Source: Amarin Corporation plc
"BEDMINSTER, N.J. and DUBLIN, Ireland, June 12, 2018 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN), a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, announced today that it has entered into a multi-faceted collaboration with Mochida Pharmaceutical Co., Ltd., an integrated Japanese pharmaceutical company. The collaboration is focused on the development and commercialization of early-stage drug products and indications based on the omega-3 acid, EPA (eicosapentaenoic acid)."
Amarin paid Mochida $2 million,up front, upon completion of this COLLABORATION agreement....The time has come, after the passage of six long years since this agreement was signed...to have Amarin now begin work to bring to the market patented LrR-Et EPA, a med,even superior to their current Vascepa.
I would rather see Amarin spend $50 million on this project rather than on buying back Amarin stock.
DMC8...."In Hikma’s press release Hikma refered to multiple uses of generic Vascepa....Amarin's lawyer emphasized that physicians observed Hikma’s press release and saw that its drug was the generic equivalent of Amarin’s drug. This, the lawyer argued, creates a question for the jury of inducement of infringement."
Why would Hikma NOT disclose on their generic meds' label that "this med is ONLY to be used for treatment of patients with triglycerides of over 500 mgs/dcl"?...The obvious answer is that Hikma would NEVER do this because...if they informed patients and Docs of that uncomfortable but legal fact, they would then lose 97% of the generic EPA's market share for the U.S.,which they now pull in by infringing on Amarin's CVD patents and which 97% of market share should, by law, be going to Vascepa.
"Amarin has secured a worldwide patent priority claim to a LYMPH-RELEASING composition of eicosapentaenoic acid ethyl ester (LR-EtEPA) technology/invention and methods of using the same to increase EPA uptake in tissues to treat and/or prevent the onset of a number of diseases including:
- Cardiopulmonary, cardiovascular, and cerebrovascular diseases
- Pulmonary disease including sepsis, SIRS, and/or ARDS
- Neurological diseases
- Cancer...including cancers associated with the lymphatic system"(e.g. LYMPHOMAS)
I would hope that some mention of this product will be made by CEO Holt at the Amarin upcoming Q4 2023 results C.C. on 5/2/24
From SA article..."The actual launch of the product took place in Q4 2023. However, the issue of reimbursement of the drug by the government remains open and on this point, it is expected that the process will not be defined before the end of 2025."...
I disagree...The Chinese national health system has had Vascepa under study since before Q4 2023...Medical journals have been reporting on the superior efficacy and safety benefits of Vascepa...The data on Vascepa has been under review since Q4 2023 and probably even prior to that time...Recent articles have informed scientists and doctors the about the positive effects of Vascepa for patients...I would not be surprised to see a report of the approval of Vascepa for patients in mainland China released any time soon...followed by negotiations to be conducted by the Government health system and by Eddingpharm over reimbursements.
After being invested in Amarin for close to 15 years, my current conclusions are that...the main upside for Amarin now depends on catalysts such as...
-reimbursement for Vascepa in mainland China
-reimbursement for Vascepa in major European countries
-court decisions discouraging further infringement on Vascepa CVD patents by generics
-a patented new EPA product being introduced into U.S. market
-new evidence of effectiveness of Vascepa in other diseases in addition to CVD...such as in Alzheimers or cancers
Waiting for these catalysts to materialize, it would be well for Amarin to preserve its cash, in order to withstand any negative catalysts that might arise....and, if the opportunity arises, to spend the cash on something that might increase its revenues
for those reasons, I am not eager for Amarin to spend $50 million on the buy back of its stock.
One of the good things about Amarin's current situation is that it has plenty of cash and no debt.
Colchicine has many serious side effects and would be dangerous to pair with Vascepa for long term use.
Amarin to Report First Quarter 2024 Financial Results and Host Conference Call on May 1, 2024
DUBLIN, Ireland and BRIDGEWATER, N.J., April 15, 2024 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced that it will host a conference call with Patrick Holt, President & CEO, and members of Amarin’s senior management team to discuss its first quarter 2024 results followed by Q&A on Wednesday, May 1st, 2024, at 8:00 a.m. ET.
The conference call with management will follow the release of the Company’s first quarter 2024 financial results in the pre-market hours.
To enhance engagement with the company’s shareholder base and facilitate connections with its investors, Amarin is partnering with Say Technologies to allow retail and institutional shareholders to submit and upvote questions, a selection of which will be answered by Amarin management during the earnings call.
Starting on April 15th at 8:00 am ET, all shareholders are encouraged to submit questions by visiting: https://app.saytechnologies.com/amarin-2024-q1. This Q&A platform will remain open until 48 hours prior to the start of the earnings call. Shareholders can email support@saytechnologies.com for any support inquiries.
Conference Call and Webcast Information:
Access to the live call:
Go to the investor relations section of the Company's website at?www.amarincorp.com
Dial in within the United States: 888-506-0062
International dial in: 973-528-0011
Access Code: 207947
Access to replay:
Dial in within the United States: 877-481-4010
International dial in: 919-882-2331
Access Code: 50260
A replay of the call will also be available through the Company's website shortly after the call
A problem for Vascepa is that , in the eyes of the public, it is just another healthy supplement, much like fish oil...Oncology drugs have massive price tickets and are still in demand because patients understand that they make the difference between life and death(or at least can extend life).
Amarin needs to make clear that Vascepa makes a difference between life and death, not just CVD.
Studies of Vascepa discuss reduction of CVD in patients, but they usually don't emphasize the difference that Vascepa can make in long term survival...By now, world figures on years of survival with Vascepa, as opposed to no Vascepa, must be available.
I personally believe that Vascepa has helped me to live to the advanced age that I have attained...I think about Vascepa in terms of my mortality instead of solely dwelling on my reduction of CVD rate.