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I was tempted to swap out my statin for the better tasting Oreos, but they are a bunch more expensive.
Joe, I am eating more of those homemade BLT sandwiches since I moved to the NW. To tie in with Nuke's question, there are a number of highly acclaimed restaurants around the Portland area - kind of a foodie town where people will wait in line for hours in the rain to get a table. Unfortunately for me, after a few visits, I'm broke. Expensive as hell compared to what I was used to in Florida. Take care of yourself.
Thanks. I was just looking at daily volumes. I mean the drug should work, but like you say will the Side effects be acceptable enough.
As Capt pointed out, EE forms of EPA are poorest at absorption, but it has to be stated that that comparison with other forms of EPA happens at a fasted state. When taken with fat the absorptions of the various forms of EPA become quite similar:
"Fasted State versus Fed State
An important finding in the majority of studies trying to understand the absorption behavior of omega-3 ethyl ester (EE) was that it is of utmost importance to take the omega-3-EE medication after a fatty meal (fed state) and not on empty stomach (fasted state). Unfortunately this fact is not detectable from the data shown in Table 2 because the Relative Bioavailability Index for the EE-form was always set to 100, even if the bioavailability with respect to absorbed absolute quantity of omega-3 (in mg) was very poor. A good illustration of this food effect can be seen in the absorption charts from the ECLIPSE study [18] where the bioavailability between an omega-3-ethyl ester drug (EE) and a omega-3-free-fatty-acid drug (FFA) was compared. The total EPA and DHA content of both drugs are comparable. From Figure 5a can be seen that the EE formulation (green line) in the fasted state (low fat diet) is only very poorly absorbed. Whereas the FFA form gets well absorbed with a typical Cmax at approx. 5 hours after intake. Taking the same formulations after a high fat diet (fed state) the absorption behavior of the EE improves dramatically and shows a similar curve-shape than the FFA-form (Figure 5b). However, looking at the total EPA+DHA plasma concentrations of the two charts (Y-Axis), it also becomes clear that the absolute quantity of absorbed EPA-FFA and DHA-FAA (in mmol/ml blood) improves almost twofold when the drug is taken after a fatty meal.
Therefore, in order to maximize the absolute quantity of EPA+DHA absorbed into the blood one should always ingest the omega-3 nutritional supplement or pharmaceutical drugs together or shortly after a fatty meal. Our digestive system, in particular the pancreatic enzymes and bile acids need to be triggered and released by a minimum amount of fat in our diet. This is especially important for the omega-3 EE form. Taking such a supplement or drug before or after a light breakfast (for example only fruit and coffee) will not release any pancreatic lipase that can split the EE into the absorbable FFA form. The majority of the ingested omega-3-EE will thus not be able to be absorbed and are lost with the feces. On the other hand, products offered as TG or rTG start to provoke a pancreatic response even in a fasted state and thus can be absorbed after being converted to the FFA and monoglyceride form. The efficiency of this “lipid digestion” can be even more improved by taking the TG/rTG omega-3 together with a fatty meal. In this case a maximum pancreatic lipase activity can be achieved which maximizes the efficiency of transforming EPA/DHA-rTG into the bioabsorbable FFA and MG esters. However, many people taking omega-3 products suffer from hyperlipidemia and thus should avoid a too fatty diet. In this case the omega-3 supplement/drug should be ideally in the FFA-, TG- or rTG-form.
As general rule can be said, that all EPA and/or DHA chemical forms are far better absorbed and thus more bioavailable, if taken together with or shortly after a fatty meal (Figure 6). Thus, bioavailability is directly influenced by (i) the chemical form of the omega-3 fatty acid and (ii) whether this omega-3 fatty acid was ingested in the fasted or fed state."
https://vitalremedymd.com/blogs/professionals/omega-3-bioavailability-dependson-the-chemical-form-concentration-and-fed-state
Also take it with some fat.
I think I see that higher volume if your avg volume is over the last 52 weeks, but it doesn’t look like higher volume compared to the last 3mo avg?? Am I looking correctly?
North this along with HSCS has taken a beating. Are they going kaput?
Well you used the word purify, which of course you need to do if you want to concentrate it.
Thanks for catching that and correcting the "huge". You discuss the need for separating from the glycerol in order to purify the EPA, but neglect to mention that the other reason is that it is almost impossible to significantly concentrate the EPA as long as the fatty acid is still bound to the glycerol. Good explanation on the purification.
You raise a good point about why the FDA has not gone after some of the supplement manufacturers. Of course the supplement manufacturers were selling omega-3 products long before any approved drugs came out, BUT although I am not sure, those products were confined to simply fish oil and were limited by the fact that they comprised no more than 18% EPA and 12% DHA. I remember after Lovaza was on the market that suddenly we began seeing higher concentration omega-3 products come on the supplement market. So I don't really know the timing of when supplement manufacturers started using the ethylated products - before or after FDA approval of Lovaza. But that timing might be an explanation as to why the FDA is not clamping down.
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."
I like your tenacity but I have to agree with Sleven on this. The reason for ethyl ester being in the patents, is that it is the way they can concentrate enough EPA to get 1,000mg into a swallowable pill, by detaching the EPA from the huge glycerol portion of the triglyceride molecule.
Zip, I think you summarize the situation pretty well. I mostly agree even with your comment about the buyback, with one caveat. Namely, if the buyback jogs the market into changing its negative view of Amarin and begin to realize the potential V and Amarin have, then it might be a good thing.
JRoon, congrats on the good numbers. I sold and myself used the Carlson EPA Elite Gems. Carlson has, in my mind, has a bit of a confusing product naming situation (too many products) in that their Gems can be a combo of EPA and DHA and their Elite EPA Gems only EPA.
And, they use the ethyl ester form in the Elite EPA Gems, which need to be taken with food to make sure they are well absorbed.
Thanks. Didn't need all that other stuff after ".......active EPA is triglyceride form."
"active" EPA and EPA that I get from a sardine are the same.
Sleven, I was asking about the distinction between EPA and active EPA based on this portion of Orbapu's post:
"Icosapent ethyl is de-esterfied, converted into active EPA, and then absorbed in the small intestine."
What is the difference in either molecular formula or chemical structure between EPA and "active" EPA?
One or the other.
Have a safe trip.
Thanks Sleven. I realize what remand means. It could mean a new trial, new sentencing hearing/order, a correction of the trial court’s order or other actions. I guess where I was confused is that it sounds like the Appeals Court cannot simply reverse the lower court's decision and rule for the other party.
What I was referring to is that there is very small chance that the Appellate court reverses the lower court decision. But barring that remanding back is the next best thing. We get another bite at the apple
Sleven, not as good as an outright overturn but a lot better than where we stand.
Well sure as to what you say. However, you also say: "...future sales and marketing campaigns". That of course is the major reason for the lack of growth, the stopping of all marketing. And, that was because of the entrance of Generics. Until you can shake the Generics not much can be done.
Thanks JRoon. I used to have a subscription when I was in the business, but have been retired now for more than 5 years. They were rather superficial with what they tested for. Our biggest gripe was that they didn't test every product on the market and it seemed willy nilly as to what they selected to test. For instance, many times the best seller or the product with the best reputation was not tested. But it did have some value to us.
Interesting mention of Icosapent Ethyl. I am sure this is based on the Evaporate trial by Dr. Budoff. What caught my eye was the comment that it was only shown to reduce plaque in those with trigs above 150. So I did look up the Evaporate study and sure enough the median trig level was over 250. Of course this doesn't mean it couldn't help someone with lower trigs but just not proven in a trial:
Well stated.
Overall market has taken a drubbing the last few days and volume here is small so not Amarin specific. Steady as she goes. I am like the Dread Pirate Roberts, taking iocaine powder over time so I am now immune.
I think to Kiwi’s list I would add that curtailment of advertising, salespeople, etc can go a long way explaining the small market.
Do you know how to translate the 7693kg into dollar value to compare the quantity to what Amarin already has on hand?
Don’t see any news —- anyone know the reason for this morning’s drop?
Thanks Capt. Do you know what Vascepa's percentage of the market was before R-I results? Curious to know if it was even the 10% being bantered about as a supposed total portion of the O3 market.
For me, if GV was ONLY being prescribed for very high trigs (>500) I would think it should be even far less than that because Lovaza (GL) is far better at dropping trigs (I realize at the expense of raising LDL - but it is only supposed to be used for a very short time so I believe docs would make that tradeoff)
As long as you don’t hear….”Objection….Sustained”
Thanks Sleven.
So is this recent weakness an indication that the open label info is leaking out or is the volume way too low to jump to that conclusion? I would assume a much bigger drop in price if related to bad news from the trial rather than this consolidation as I might describe it.
And, if it was significantly different then I imagine a whole set of hoops to jump thru will be required by FDA
I am obviously quite dense when it comes to certain details concerning a possible new formulation. If you or anyone else wants to opine and educate us on these questions I would appreciate it and it may benefit all of us here:
1) What will the FDA require Amarin to do to be able to market a new formulation?
2) Will Amarin stop marketing the current formulation if permitted to market the new formulation?
3) Will Amarin be able to prevent Generics from selling this new formulation?
4) Will docs, pharmacies, insurance companies still divert scripts for the new formulation to whatever the Generics are selling?
I am postulating those questions as being for now strictly related to the U.S. market.
North I was a little surprised to see you say that your eye docs were happy. I had often heard that these drugs could be a negative wrt eyes because of the presence of receptors. But if you look there seems to be mixed research on this:
https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=6&contentid=1657098899
Wonder how much more benefit can be had by adding tadalafil to Vascepa?
https://www.medpagetoday.com/meetingcoverage/aua/104272
As far as the revenue stream in the U.S., I feel there is not much they can do without some court victories to dislodge the Generics. If they can’t stop the Generics then any action they take will be extremely muted and most likely not worth the money.
These studies highlighting the wonders of V are going to screw up trying to keep the stock price low for the buyback
Yes, Laurent, the chart clearly shows for total events, the lines separating well before 12 months. In trying to understand and explain these results and trying to mesh them with R-I results (particularly the fact that they seem better) two thoughts come to mind, both of which are probably not the answer but here goes:
1) I can see anything in that little abstract about the study whether all patients in the cohorts were on a statin? Most likely they were, but since it doesn't seem to be mentioned (or my aging eyes missed it) that might mean we shouldn't be able to totally compare this to R-I if many were not on a statin.
2) Could mineral oil be more protective than mixed omegas making IPE in R-I not look as effective? Well, we really don't believe that, just as we don't believe mineral oil was so detrimental to the placebo group to make IPE look so good.