Tatsumaki
12 hours ago
by detaching the EPA from the huge glycerol portion of the triglyceride molecule
Glycerol is not huge... it's a 3 carbon chain with hydroxyls on each carbon. A triglyceride is a glycerol backbone with a fatty acid (3) linked to each carbon. Thus a tri-glyceride. Trying to get rid of a bulky glycerol isnt why ethylation is done.
The actual reason they separate the 3 fatty acids from the glycerol and ethylate the individual fa's is in unrefined fish oil there can be any combination of fatty acids found on the glycerol backbone. It's not all EPA on one trig molecule, all DHA on another etc... cant purify trigs as it's variable combos on each plus some other stuff like DPA, ALA, and shorter chain stuff. So they have to break it all down into individual free fatty acids in order to fractionate and purify those individual fatty acids into separate products. Ethylation stabilizes the molecule during and after the process. It's the only way any refined fish oil supplement or drug can hit the higher purities needed and exclude DHA and others trace fa's. Legally, the supplement makers should re attach the purified EPA back on to a glycerol to form an EPA only triglyceride that they label as rTG... but the intermediate step in doing that is still the same E-EPA process driven to the desired purity taken one more step.
Incidentally the MAG-EPA discussed a few times is just the glycerol backbone one EPA stuck to it... the other 2 carbons just have the hydroxyl group. DAG-EPA would have 2 EPA, and one hydroxyl. Seems like lots of ways for people to get "its the EPA stupid" in the US that don't funnel into Amarin's bottom line and stock price.
The question you should all be asking is why isn't the FDA addressing supplements containing E-EPA as it's an actual registered drug product. Normally they go nuts if a supplement contains an API and pursue action aggressively. They have to protect their drug approval racket or people wont pay for the mafia protection and exclusivity if there is none. They went after and banned red rice yeast supplements cause they had the og statin in trace levels after statins hit the market. Yet they're pretty quiet with multiple supplements using ethylated EPA. Everyone sweating generics when many like Jroon aregetting off the chart blood levels delivered right to their door with no Rx needed.
dogn
16 hours ago
High on Lipoprotein-
https://www.jacc.org/jacc-edge/current
You know you are at a cardiology conference when the busiest booth isn’t the one providing free ice cream, but the one offering complimentary Lp(a) screenings. Likely the greatest concentration of lipid-obsessed people in one room, ACC.24 was constantly buzzing with discussion of Lp(a) and its ramifications for patient care. Elevated Lp(a) levels confer greater cardiovascular risk even when LDL levels are optimal and are not affected by current therapeutic options. The REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) trial aimed to assess the benefit of icosapent ethyl (IPE) across a range of Lp(a) levels. Nearly 7,000 patients on statin therapy with CV disease were randomized to receive IPE or placebo, had a baseline Lp(a) level assessed, and followed for any major adverse CV events. While IPE did not directly lower Lp(a) levels, the study demonstrated that IPE consistently decreased the occurrence of major CV events, irrespective of the actual Lp(a) level. Additional studies will be needed to better understand how to best address this risk factor.
rosemountbomber
16 hours ago
When the FDA checks the Generics for bioavailability, they are checking for EPA not the ethyl ester form. It is absorbed as EPA. Active moiety as Sleven said, but you seem to disregard this.
Think of say, the blood pressure drug, Metoprolol. It is available as Metoprolol tartrate and metoprolol succinate, with the succinate form having greater liposolubility.
https://pubmed.ncbi.nlm.nih.gov/20638827/
"The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations - ethyl esters, free fatty acids and re-esterified triglycerides - with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA."
Mr Stockboy
17 hours ago
I think this discussion is necessary, but I disagree with the suggestion "EPA is the active moiety" and could not be affected negatively or positively by turning it into an ethyl ester. Amarin had clear reasons for turning it into an ethyl ester and every patent going back to the beginning, states E-EPA.
IHUB friends: Any change in the chemical chain is the basis for the patent Amarin claimed. Amarin claimed E-EPA, not EPA. For some patented reason, Amarin determined adding the Ester Ethyl was necessary, and every since has cited it in every claim section of patents. The fact is turning EPA into E-EPA is not a mote "moiety" point. There are efficacy issues, safety issues, a lot of issues!!!!
In court, Amarin is there to defend E-EPA.
Mr Stockboy
18 hours ago
I entirely disagree (respectfully).
Amarin altered in the lab EPA into E-EPA for a valid, patented reason. They in the patents even cite other possible indications. Keep in mind number sleven, E-EPA, a chemical composition could have negatively or positively affected the EPA moiety. Amarin clearly did early studies which led them to the Ethyl Ester version, and for a REAL reason.
In a court of law, a lawyer, an astute lawyer would have argued EPA is not E-EPA, as the chemistry is not the same, and it's not the same. If you cannot see how a lawyer cannot argue EPA is not E-EPA, then I wonder in due respect. A Lincoln is not a Mercury though made by the same firm.
Hikma lawyers focused on the prior art of EPA, not E-EPA. I think Marjac would side with me, as would other lawyers. But let's keep the discussion going. All the best!
Mr Stockboy
18 hours ago
Amarin Needs to Defend the Right Molecule in Court: E-EPA (C22H34O2).
All of Amarin's patents claim E-EPA.
In Nevada, Amarin argued with Hikma over EPA (prior art). Big glaring mistake!
E-EPA is a novel, lab created, molecule, not found in fish oil.
Hopefully, there is time and opportunity for Amarin to return to court and defend E-EPA, not EPA.
Mr Stockboy
19 hours ago
Patent 11690820 "4. The composition of any one of claim 1, 2, or 3 wherein the ethyl-eicosapentaenoic acid is present in the composition in an amount of 250 mg to 1000 mg. 5. A pharmaceutical composition comprising 250 mg to 1000 mg of fatty acids at least 95% of which are in the form of ethyl eicosapentaenoic acid, wherein the composition contains no docosahexaenoic acid, and the composition is present in a capsule. 6. A pharmaceutical composition comprising 250 mg to 1000 mg of fatty acids at least 95% of which are in the form of ethyl-eicosapentaenoic acid, wherein the composition contains (a) less than 5% in aggregate of arachidonic acid and n-3 docosapentaenoic acid, and (b) no docosahexaenoic acid; and wherein the composition is present in a capsule."
Patent 8557280 "1. A method of reducing triglycerides in a subject in need thereof who is on statin therapy comprising, administering to the subject 2500 mg to 5000 mg per day of ethyl eicosapentaenoate for a period effective to reduce triglycerides in the subject. 2. The method of claim 1 wherein the ethyl eicosapentaenoate is administered to the subject in dosage units each comprising about 500 mg to about 1.5 g of ethyl eicosapentaenoate 4. The method of claim 1 wherein the ethyl eicosapentaenoate is administered to the subject in dosage units each comprising about 900 mg to about 1 g of ethyl eicosapentaenoate. 6. The method of claim 1 wherein the ethyl eicosapentaenoate is administered to the subject in dosage units each comprising about 1 g of ethyl eicosapentaenoate. . The method of claim 1 wherein the ethyl eicosapentaenoate is present in a pharmaceutical composition comprising other fatty acids or esters thereof and said ethyl eicosapentaenoate comprises at least about 90%, by weight, of the fatty acids present in the composition."
Patent 8557799 "3. The method of claim 2 wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting VLDL-C compared to a fasting VLDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 4. The method of claim 3, wherein upon administering the composition to the subject daily for said period, the subject exhibits at least a 15% reduction in fasting triglycerides compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 5. The method of claim 4, wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting LDL-C compared to a fasting LDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. . A method of lowering triglycerides in a subject on stable statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl and a fasting LDL-C level of about 40 mg/dl to about 100 mg/dl comprising, orally administering to the subject daily for a period of at least about 4 weeks a pharmaceutical composition comprising about 4 g of ethyl-EPA and not more than about 4% DHA or its esters, by weight of all fatty acids present. 10. The method of claim 9 wherein upon administering the composition to the subject for said period, the subject exhibits a reduction in fasting non-LDL compared to a fasting non-LDL level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 11. The method of claim 9 wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting VLDL-C compared to a fasting VLDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 12. The method of claim 9 wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting non-HDL-C compared to a fasting non-HDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 13. The method of claim 9 wherein upon administering the composition to the subject daily for said period, the subject exhibits a reduction in fasting total cholesterol compared to a fasting total cholesterol level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. 14. A method of lowering triglycerides in a subject on stable statin therapy having fasting triglycerides of about 200 mg/dl to less than 500 mg/dl comprising, administering orally to the subject on statin therapy a pharmaceutical composition comprising about 4 g per day of ethyl-EPA and not more than about 4% DHA or its esters, by weight of all fatty acids present, for a period of at least about 4 weeks thereby to lower fasting triglycerides in the subject by at least 15% compared to a fasting triglyceride level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period, and wherein administration of the composition results in a statistically significant reduction in fasting LDL-C compared to a fasting LDL-C level in a subject maintained on stable statin therapy without concomitant ethyl-EPA for said period. "
It's E-EPA, Amarin has a clear path to reinstate the patents.
north40000
19 hours ago
Question to both Stockboy and BbI: Were all claims of Amarin’s 6 patents involved in the Nevada suit limited to IPE, icosapent ethyl, as opposed to defined amounts of highly pure EPA? Thanks to both of you for your analysis. Restoration of some claims of those patents, particularly the dependent claim you focus on, could still be waved in front of H’s face to force a possible settlement. The Supreme Court’s opinion in Hazel-Atlas remains in play, IMO. DRL and TEVA should also be concerned.
Mr Stockboy
19 hours ago
According to my read, Amarin lost to Hikma because Judge Du and the lawyers argued over the prior art issue of EPA (Mori, etc). Yet E-EPA is not in prior art and is a novel creation in the lab. In this case, this is clear fault of Amarin's lawyers not to point out the obvious: Hikma argued there was EPA prior art (debatable), but what would have ended the whole case is if Amarin's lawyers pointed out they were there to defend E-EPA of which there is no prior art. I also wish Captain and others on this board would grasp: "IT'S THE E-EPA STUPID!" on his many wonderful charts. 😃
For those still wrestling to grasp why E-EPA is important, is because Amarin's inventors would tell you the reason (safety, absorption without harm, many reasons, etc.) why they added the ethyl ester to the EPA chemical chain). I can already guarantee all of you there were clear reasons why Amarin's inventor added the Ethyl Esther. I hope this helps advance knowledge.
Mr Stockboy
20 hours ago
IMO the buy-back will cut into share supply and set the stage for a faster-rising share demand as if I remember Amarin has hefty percentage of long-investors (private and institutional). Furthermore, Amarin is selling E-EPA (C22H34O2), not EPA (C20H30O2), thanks for ORBAPU for clarification, just dig into patent 11690820 "Claim 5. The pharmaceutical composition of claim 1, wherein the eicosapentaenoic acid is ethyl eicosapentaenoate"... E-EPA is a novel creation in the lab; EPA is found in fish. I regret not one legal-beagle to date has yet to grasp what Amarin's lawyers were supposed to be defending in court: E-EPA, not EPA. There was definitely no prior "art" regarding E-EPA which meant the opposition's citing of prior art was EPA, not E-EPA created in the lab, not found in fish. Just look at the chemical chain; they are not the same. "Your honor Judge Du, we are here to defend E-EPA, not EPA, as there is no prior art for E-EPA. Our opponents Judge are talking about the wrong molecule. We rest our case."
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