Not only that Raf, but he needs to be told that the ones he is highlighting as HIGH in mercury are also relatively very low in omega oils compared to salmon or mackerel.

Thanks Zu, good post.

As they point out the fact that statins appear to lower inflammation and the best outcomes are in those who start out with high inflammatory marker levels, the question then becomes is there a law of diminishing returns by adding another anti-inflammatory ( Vascepa in R-I) to the statin.

As we ponder that though, we must remember that Jelis showed no such diminishment.

Yes HD thanks for correction but my point is that in Anchor we were basically talking about measured markers and now with Reduce-It we are looking at outcomes and events. How many prior studies of various drugs looking at outcomes had mineral oil as part of placebo? Don't know the answer to that so someone can shed light on this possibly.

HD - a good post. Thanks for the quotes.

To summarize, they looked for any prior data to show whether mineral oil had biological activity and found nothing significant and then concluded that the differences between the active and placebo groups should be attributed to Vascepa.

Kind of wondering about the reference of it being addressed to the DMC for Reduce-It. In Anchor the concern was any possible effect from the mineral oil affecting TG numbers, but in Reduce-It the primary focus is MACE so if anything should be discovered in relation to the mineral oil, I would think it would have greater implications than strictly V and the Reduce-It trial.

EPI, I think you have to subtract the 2.7 million share trade (some kind of arranged sale) which would then yield a normal volume.

Only logical explanation.

STS well aware than many researchers were paid to not divulge negative results in various studies. However the story made reference to a change in policy or law in Europe in 2004 which did away with that there, and I was wondering if the same thing happened here.

This what I don't understand.. Suppose a company studies a substance and makes application to FDA for approval. Would not all the data in the trial be made available to the FDA including anything negative?? I could see where a company finds something negative in a study and hence decides not to apply for approval to the FDA hence being able to hide the problem.

BC, I don't understand that either. One trade almost double the average daily volume and no price movment????

So what are the regulations here?? Can negative findings be hidden?? Some statin studies must have been done here Stateside.

Same thing with coumadin, it is an antagonist to vitamin K and causes calcification of the arteries.

This morning someone posted a story about statins and their negative impact on CV problems. My question would be why did those not show up in outcome studies for statins? Studies too short of a duration?

STS, if we have a quarterly report after 967 is hit but before any DMC decision, will the company at the CC let us know that 967 was hit and that they are in the data collection/review stage?

Zu,

AND I would think that continuing the trial would hopefully only encompass your last two options. Wouldn't the DMC recommend stopping the trial for futility? Or report futility to the company and they would decide at that point.

Hence hopefully if the trial proceeds past interim that the market realizes that a positive outcome could be highly anticipated.

Don't worry they will get to see the results before approval.

Very good post Zu to combat some of the irrational thoughts in relation to the FDA.

NO doubt they screwed Amarin for sure, but as you say stellar results will not permit the FDA to repeat what they did to us in the past.

Kiwi,

It is interesting too that this stock price drop has moderated some of the euphoric enthusiasm regarding the success of R-I. I do believe that people adding EPA to their diet or medications will on the whole reduce their risk of CVD and a host of other conditions, however, I am not overly confident that Reduce-It will show such a huge reduction in risk that it will be stopped at interim. Now with this stock drop we see posters using terms such as: "R-I has risk" and "pending R-IT results (which are no slam dunk)".

I kind of view Vascepa and the Reduce-It trial kind of like having the last shot in a tied basketball game. Worst thing that happens if I miss the shot ( if Reduce-It not stopped at interim) is I go to overtime. With Vascepa the great thing is there is no way that the active group should do worse than the control group. No information that I have ever seen shows people do worse on EPA. Question will be how much of an improvement will the active group show over the statin only group. From what I have seen the longer someone is on EPA the greater the benefits so if not stopped at interim, for me that does not mean it is not working. It should show greater efficacy over time.

Interesting posting comparing various drug agencies around the world. Sent to me by a pharmacy I use occasionally:

How Do Other Drug Regulators Compare to the FDA?

30th Jan, 2015 by admin.

The United States Food and Drug Administration (FDA) is a regulatory body vetted by the US Federal Government. It is responsible for securing the safety of its citizens and livestock in the realm of consumables like food, medicines, chemicals and all of their biological delivery methods. The FDA charter, by default, makes it intimately tied to various industrial and economic entities within the United States.

Since the United States is the principal world leader in economics, the FDA is often viewed as the most efficient, thorough, and authoritative food and drug organization in the world. While the US FDA oversees the majority of food and medical innovation internationally, it is not the only world class regulatory department actively engaged in the safety of the world’s population. Comparable government committees throughout the industrialized world have matching, if not higher, standards than the US FDA. Without the “red tape” associated with overseeing an astronomically-huge country, many other regulatory bodies enjoy similar safety records, but have more streamlined processes.

A functional, if not scientific, method of surveying a food and drug regulatory body is a tri-fold comparison of the amount of time it requires to approve a product for consumption, the volume of new products, and the number of approved products that are recalled because of complications.

The four-phase approval process of the US FDA results in an average of 12 years from inception to approval. Statistically, only 1 in 5000 new products make it to market. In 2014, there were nearly 40 FDA-approved products and devices recalled. 40 recalls represent thousands of affected lives, and billions of invested dollars. Does the US FDA have a corner on efficiency and efficacy?

The food and drug regulatory bodies of the world are divided into six categories according to location. Here are the ratios of approval time, volume and recalls for each region.

AFRO: Africa

- completely import dependent region
- 50/50 introduction to success rate of approved new drugs and devices
- nearly all approvals have market and human success

AMRO: The Americas

- outlined above

EMRO: The Eastern Mediterranean

- 80-90% approval rate
- few recalls because of youth complications

EURO: Europe

- 9% marked decrease in food and drug reports and notifications by hazard in 2013, meaning an extremely efficient rate of product approval

SEARO: South And East Asia

- food and drug approvals according to need, population and mortality issues largely controlled by local Health Services Departments (HSD)

WPRO: The Western Pacific

- dependency upon western food and drug regulatory bodies
- nearly all resources devoted to HIV and malnutrition issues

A complete survey of all major food and drug regulatory bodies in the world separated by region can be viewed here. Many of these national agencies are established to oversee the importation of products, foods and medicines that are approved by larger authorities like the US FDA.

The purpose of a food and drug regulatory body is to provide oversight of the many products innovated by companies and individuals before they are introduced to the public. The matter of safety and efficiency is not necessarily commensurate with the size, richness and influence of a particular body. The US FDA is responsible for approving many innovations that the world’s population can benefit from. It is however, mired in certain processes which make it less-than-ideal. There are many methods and protocols from each regional food and drug regulatory body, that the US FDA could learn from. Humans need the best food and medicine innovations without the interference of ridiculous governmental blockades. After all, lives are at stake!

Sources:

http://www.fda.gov/Drugs/drugsafety/DrugRecalls/default.htm

http://www.medicinenet.com/script/main/art.asp?articlekey=9877

http://www.aho.afro.who.int/en/atlas/health-system

http://www.emro.who.int/media/news/syrias-first-specialized-burns-unit.html

http://ec.europa.eu/food/safety/rasff/docs/040614_infographic.pdf

http://ec.europa.eu/food/safety/rasff/docs/040614_infographic.pdf

http://hiip.wpro.who.int/portal/default.aspx

http://www.who.int/medicines/areas/quality_safety/regulation_legislation/ListMRAWebsites.pdf

I believe the doc can indicate on the script no substitutions

Well was that one of listed criteria for entrance into the study?

Knowing the medical establishment they probably won't do a 180 but if they do anything they will simply ADD EPA/AA to their standard LDL treatment. Actually that is exactly what Reduce-It would show (if positive) that adding EPA to statin treatment affords some extra benefit.

I wonder if someone can explain this finding?

Apparently higher bilirubin levels equate with less atherosclerotic plaque in the carotid arteries in coronary artery disease patients. I thought however that higher bilirubin levels were indicative of problems with the liver.

http://www.ijcme-journal.com/article/S2214-7624(14)00028-0/abstract

EPA to Oleic Acid ratio associated with MACE. Another brick in the wall.

http://www.ijcme-journal.com/article/S2214-7624(15)30014-1/abstract?cc=y=

On the downside, of course this is a Japanese study.

Satire

Your logic seems to make sense that the negotiation is concerning something else, however, it could still be part of the negotiations as a bargaining chip where the company might be willing to permit some kind of limitation on it in return for something else. Unfortunately pure speculation and frustrating to think about so for me just easier to wait and see what comes of it rather than twisting myself into a knot.

Sounds like the medical equivalent of "paint by numbers" that we had as kids.

Having been in Elan a long time it kind of reminds me of the PML occurrence related to Tysabri.

Yes and that is why I suggested that even if not stopped at interim the word may get around enough to buoy the stock price even before results and mute any possible dilution.

Some of us long time holders do not have the luxury of bailing (on no or poor news from settlement) and then repurchasing after dilution. (Long term cap gains). (What cap gains? - only future possibilities).

But it is possible for events to transpire a little differently even if the trial is not stopped for efficacy.

If the trial is not stopped for futility or safety concerns, and the date of the 967th event is divulged, assuming it is somewhat down the road, some market observers may astutely figure out that unless the placebo event rate is some ridiculously low figure, that V is working. Stock price may actually lift somewhat and the dilution may not cause such a big ripple.

FWIW, we really don't know how this will turn out.

Obviously V would not be a cause of dropout but ALL patients in Reduce-It are on a statin and that is notorious for having people develop side effects and seek to stop treatment.

Good post and article amr456. I don't guess our Reduce-It patients were screened for APOC3 mutations?

BB, obviously if done at the pharmacy level it is a totally inappropriate practice since generic L or L for that matter is not the same product as V.

Now do you think once NCE is granted then there would be no way a pharmacist would be able to switch the script? (since that status signifies a new chemical entity - hence nothing like it).

Zip that would be good news indeed if Kowa invested in Amarin.

Careful, STS, you are providing non-blinded (think Jelis) anecdotal evidence which the FDA will not accept! I am in the same boat, with retirement account suffering on all positions except AMRN!

Kiwi thanks for taking the time for your reasoned response. Your answer demonstrates the complexity because of a number of variables, including diet, exercise, medications, family history, genetics, particular population group, etc.

I asked that question because ultimately I have been trying to mesh the growing belief here on this board that Vascepa will show a positive RRR (if not enough to stop at interim then when trial completes) with the market's indifference.

So if you have statins to start with only a piece of the puzzle with many other things to consider, then I wonder if docs will just consider Vascepa as part of the mix. I think some of the detailed analysis of Reduce-It may be very important to see how wide or narrow Vascepa's application can be.

Once euphoria for a drug wears off, (I believe we have already had that at least once with V) then I believe the old saying: "Now the heavy lifting starts" is applicable at the time of drug approval. So many stocks actually fall upon approval because the only thing approval gives you is the right to market to that indication.

So not sure if the market does not believe V will be successful in Reduce-It or whether the market is taking a show me stance assuming that even upon Reduce-It success that not all docs will automatically prescribe V to every one of their statin patients.

Sitting here thinking and waiting for Reduce-It results a question popped into my head that I wonder if anyone knows the answer to??

We are all thinking about the RRR of Vascepa vs control (control being on a statin), but does someone know what is considered to be the RRR for people taking statins vs people not taking statins??

TIA

Dancing,

Interesting info. Telomere length has been speculated by some as being a key but sure looks like inflammation could be a big key. Interesting also because I understand that there will be a clinical trial organized for sometime late next year to study metformin.

It has apparently convinced some researchers that metformin extends life in certain animals (or worms) that they have studied and they feel excited about the possibility of metformin extending life in humans as much as 50%. But this ties in nicely with your story because it appears metformin helps to reduce chronic inflammation. So another brick in the wall.

FWIW - How the Bulls are playing Amarin:

http://finance.yahoo.com/news/bulls-playing-amarin-202531381.html

How the bulls are playing Amarin



Traders are looking for Amarin to rally in coming weeks.

optionMONSTER's Heat Seeker monitoring system detected the purchase of more than 7,000 December 2.50 calls for $0.03 to $0.06 today. Volume surpassed open interest of 1,530 contracts, an indication that new money was put to work.

Long calls lock in the price where investors can buy stock, allowing them to profit from a rally with limited capital at risk. Their cheap cost can also generate significant leverage on a percentage basis if shares move in the right direction. (See our Coaching section)

AMRN is down 1.18 percent to $2.09 in afternoon trading but is up 8 percent in the last month. The heart-drug maker has missed revenue forecasts for the last several quarters, most recently on Nov. 4. The next set of numbers are estimated for pre-market hours on March 3.

Overall option volume was 15 times greater than average, according to Heat Seeker. Calls outnumbered puts by a bullish 7-to-1 ratio.

Raf, I too believe that all that cumulative evidence should buoy our confidence that V will be ultimately successfully in R-I.

However, remember that all the information and data that say for instance Zu has provided encompasses all kinds of aspects of EPA's biological activity. A portion of that information includes strictly chemical activity in vitro and covers all kinds of various aspects of EPA that may or may not be applicable to the question at hand in Reduce-It (for instance dry-eye syndrome).

Reduce-It involves strictly one specific question about whether EPA reduces cardio events in people taking a statin vs people taking a statin alone and to what degree does it do it.

Especially when things are toning down for the holiday the volume is telling us something. But what?

Zu, good post. The conclusion:

"On the basis of this profile and EPA's biologic plausibility, the results of REDUCE-IT are eagerly anticipated as they will clarify the potential role of EPA in reducing CV events in statin-treated patients."


Well ain't that the truth!!!!! The anticipation on this board is palpable.