I think that is the part that is tripping her up. Amarin only wants to give truthful information about Anchor results whereas she is extrapolating that into the idea that it would permit BP reps to say whatever they wanted - truthful or not.

STS, you are right about the genetics because it has been shown that breast cancer in Japanes women increases if they move to the U.S. and adopt our dietary habits, etc.

HD Thanks for the link. Since the trial is almost 6 years old it makes sense to add up CV events.

Let's hope we hear news soon. This might really be the ticket to get the sp moving prior to and leading into interim.

BC. I was just looking at another link - Journal of Cardiology concerning the CHERRY study and it seems to indicate the subjects will be followed for 6 to 8 months. How is it possible to really delineate anything about CV events in such a short time frame??? There is also no mention of CV events.


http://www.journal-of-cardiology.com/article/S0914-5087(14)00011-2/abstract

BC, thanks for the correction. What I was looking at did NOT mention CV events:

http://www.ncbi.nlm.nih.gov/pubmed/24503140

Did you copy your list from some link???

I understand the CHERRY study uses 1,800 mg of EPA so hopefully whatever result comes out of that study we can possibly improve upon with the 4 gm EPA.

The study measures markers and things like plaque volume, etc. but is not designed to measure CV events.

Vascepa is not a cholesterol drug. Not sure if your post is tongue in cheek?

One thing that stands out to me in the PR is how Vascepa is described. Very carefully described as:

"a significant and novel treatment option in the management of severely high triglycerides".

Not pushing any limits there for sure. Maybe still don't want to piss of the FDA any more than the punch in the nose they got today!!

Some may be disappointed with the muted stock price response to this, but that is probably because NCE right now does not much for Amarin for the very instant but sets the stage for the future.
So many short sighted traders but this should clear the decks and let the focus be on Reduce-It.

Been busy all day but overjoyed with the court decision. Have not been able to check out all the posts but does the FDA have the ability to appeal this judgement??

Agree with you on the fact that LDL generally becomes a problem when it is small and dense and oxidized, however, what I was referring to is that I have seen both of you write the words: "statins useful for some and not all patients"

Inflammation is the key mechanism though for sure, but there are a number of other factors as well.

BC, sounds to me like Kiwi and you agree. Both are saying statins for some but not everyone.

Good discussion of Jupiter trial (back and forth) and other CV trials and evidence:

http://www.medpagetoday.com/Cardiology/Prevention/20948

No question I am too (EPA/AA).

We know that the Japanese have a long life expectancy than the U.S. and I suppose possibly less cardiovascular disease but it seems to be a great difference in the expected event ratios (2.2 vs 5.2 or whatever) so I wonder if there is anything besides the EPA/AA ratio that can explain that?

One thing that explains part of it is that Reduce-It is comprised of not only Americans but Eastern Europeans and others that may demonstrate to have CV to an even larger extent than Americans.

Also another thought I forgot to put down is that I don't believe there is ONE single all encompassing parameter that determines outcomes for Everyone. Our bodies are complex systems and there are innumerable number of variables at play -- some of which I am sure we haven't even the foggiest idea about yet.

Well, it matters if one group has heart disease and the other does not but obviously the differences between the two groups would not be that stark but JL has referenced secondary intervention so one group could be more seriously ill than the other. But I am not familiar with the exact differences between the two groups so I am asking.

I think you guys definitively highlight an important point about event rates and LDL levels.

The only question I have is how similar were the subjects (referring to their health conditions) when comparing the Jelis and Reduce-It populations???

AND we know that almost half of all people who have a heart attack have normal cholesterols levels so this is not out in left field. So many other factors including genetics make zeroing in on cholesterol levels only the wrong thing to do.

Thanks HD. You have given us something to think (and maybe worry) about. Namely, how statins may interfere with some of the beneficial effects of EPA.

I did not really like the take from your third link concerning Jelis:

"The first one, named JELIS (for the Japan EPA Lipid Intervention Study), is a very large open-label trial published in 2007 that tested the effect of 1.8 g/day of EPA associated with a statin in patients with or without (74% of the cohort) ischemic heart disease [40]. The control group was receiving a statin only (no placebo). The authors report a significant effect of EPA on the primary endpoint. In a secondary analysis, among the patients with ischemic heart disease (n = 4,848), 197 events occurred in the control group after a mean follow-up of 4.6 years against 158 in the EPA group (hazard ratio 0.81, 95% CI 0.66 to 1.00). This non-significant difference between the two groups was not confirmed when only comparing the hard endpoints (cardiac death and nonfatal myocardial infarction) in the two groups. In fact, there were major design issues in this trial (the trial was neither double-blinded nor placebo-controlled) and it is prudent to conclude that high dose EPA had no significant effect in secondary prevention in JELIS [40]. Whether the lack of significant effect resulted from the high consumption of marine n-3 from fish, as expected in these Japanese patients, or from the use of statins or both is not clear."

STS, agreed on the Listerine. If I am putting something with alcohol in my mouth I want something I am going to swallow and not spit out!

JL and HD, I have had a hard time trying to find information concerning AA levels in the Japanese and American populations but came across this:

http://ajcn.nutrition.org/content/85/6/1457/T1.expansion.html

Quantities in human breast milk. Interestingly in a study done in 1998 France had the lowest AA values. Also very interesting if you look at a study on Japan in 2006 the DHA levels are extremely high. There was no identification of EPA levels but the assumption is that they would be high as well since it correlates to some degree with DHA.

Also there does not seem to be a very big difference in AA levels between USA and Japan - at least not in these breast milk studies.

HD good post. Your post highlights the fact that as sure as many posters here are about the outcome of Reduce-IT, we need to be not quite as euphoric about it and come down to Earth.

A previous poster posted a link to a small study showing a statin lowered AA by 11% but your second link shows the opposite. Your third link questions whether EPA is possibly inhibited by statins.

So a lot of things that can go wrong. The third link (about the interaction between EPA and statins) if I read it correctly is discussing dosages of EPA strictly enough to prevent deficiency of the nutrient and not really optimal therapeutic doses so not really sure of its application to Reduce-It

Nonetheless good to be exposed to everything that could impact our results not just the positive stuff.

BC, it appears that proper treatment of patients with EPA should include blood tests to determine the blood levels achieved and dosage adjusted to achieve optimum levels.

Zu, my doc sends me to Quest for routine blood work. Do you know if they already do either EPA/AA or EPA blood analysis??? Would like to request it.

BC you are right but the docs will have to be informed about the benefits of Vascepa as I constantly keep hearing stories from people that their doc was not aware of the drug.

Yes but didn't they have higher levels to start with? Thought Amarin stated that 4 gm EPA per day would get people to the same level of EPA as in Jelis.

HD, yeah but it is mostly math and you have it right on.

Good news really even if only in vitro. Would have been interesting to see EPA alone and how it would compare with statin alone and combo.

I tend to agree with your remark about the vengeful FDA - especially in light of the 2 lawsuits against them by Amarin - must really be pissing them off.

So I believe in light of this and other logistical problems if Reduce-It results are good that either some partnership or outright might be down the road. Never really know the size of the egos in the heads of the officers of the company though.

I realize your question is for Zu, but here are my thoughts. Doubtful in my mind that insurance would cover V for any indication NOT approved by the FDA.

After having put that thought down it made me wonder what if we won the first amendment case and then released great Reduce-It study results. Would we then be able to inform the docs even though FDA approval might be 6 months or more away?

Yes Zu. I am curious as which of the two factors contributes more to atherosclerosis - high blood pressure or high cholesterol?? AND if one had their LDL cholesterol <100 (like the non aggressively treated group) but without needing statins to do it whether atherosclerotic regression would match those receiving the standard dose of statin (again assuming both were on bp meds to the same level.

Zip, short answer my guess is NO.

HD you outline a potential scenario that may be difficult to deal with or get through.

Namely >20% efficacy but less than <30% and not enough to stop at interim.

Theoretically that efficacy level would still be great, but if the trial proceeds after interim, we
will never know the efficacy at interim and there will be some speculation all over the map including the idea of no efficacy. Stock price would get hurt albeit not as much as Kiwi speculates depending on where the stock price is at the time.

No question it is something everyone needs to find out about themselves.

Of course a good diet like the Mediterranean diet, should be good for everyone.

Kiwi, for some, not all obviously it might be. There have been concerns about the Pritikin Diet (which may have been addressed and diet altered somewhat) originally in terms about not enough good fats in the diet. Nathan Pritikin died of a suicide back in the 70's or 80's.

This is from Dr. Barry Sears discussing the evolution of our human diet and cholesterol in the body:

http://www.askdrsears.com/topics/feeding-eating/family-nutrition/cholesterol/cholesterol-facts-you-should-know

"For most people, about 80 percent of the cholesterol in their blood is made by their own body, with the rest coming from their diet. In fact, your body needs cholesterol so much that it makes around 3,000 milligrams per day that’s ten times the maximum recommendation for daily dietary cholesterol. It is estimated that around thirty percent of people are sensitive to the cholesterol-raising effects of dietary cholesterol. Normally, when a healthy person eats high cholesterol foods, the liver reduces its own cholesterol production to keep blood cholesterol at a healthy level. In cholesterol-sensitive individuals, this internal monitoring mechanism doesn’t operate, so that their blood cholesterol level goes up when they eat high-cholesterol foods.

One theory that explains cholesterol sensitivity is humans are by nature vegetarians. Originally, human bodies were not genetically equipped to metabolize dietary cholesterol, since plants are cholesterol-free. As the human diet began to include animal products, some people’s bodies developed metabolic ways to dispose of excess cholesterol and some didn’t. People who descended from the ones that didn’t adapt are the cholesterol-sensitive ones."

So no question as cholesterol is one of the number of things that float around in the blood stream they play some role in CAD (oxidized LDL for instance) but there are a number of other factors - not the least of which is genetics. Inflammation is important. The problem in regards to focusing on the cholesterol number exclusively is that upwards of half of all heart attacks occur in people who doctors would deem have normal cholesterol.

Most on this board are very well versed on AA/EPA but I thought this was a succinct piece by Dr. Sears on the subject. Short and sweet:

http://www.drsears.com/resources/cellular-inflammation-testing/

For sure. How many doctors out there are still only zeroing in on cholesterol. I have seen their routine blood work they order for their patients usually never calls for measurements of CRP, EPA/AA or other measures of inflammation.

Of course the vast majority of cholesterol in the body is endogenously manufactured by the liver. As you reduced it in your diet you body went into making more of it. Catch 22.

Bio, I see you touched on a point I have been wondering and posting about.

Namely, you said:

"As far as reversal as disease, it may in some patients others, it may be too late..........................................This treatment and diet change should take place at an early age! "

I think Reduce-It will provide the answer to what percentage of older patients (don't believe there are any young ones in the trial) get enough of a reversal of their disease to stave off an event for the duration of the trial and give the V arm a lower event % and from that the efficacy.

I know JL has talked about how quickly the EPA/AA ratio can be righted with the addition of 4 gm of EPA daily but will the quick change in the ratio override the many years of poor habits and health condition of the patients quickly enough to impact the study dramatically.

Is Kiwi closer with his estimate of 20% efficacy or others with 50% estimates? Any can opine as much as they wish - it won't alter the trial results one iota and we will just have to wait - with fingers crossed.

Thanks AP, even if it is a negative view of the case. There is so much in there to talk about but one line caught my attention:

".....Amarin’s reliance on FDA’s former practice and initial suggestion of NCE eligibility ......."

The development of a drug (research, trials, etc...) is very expensive. Everything, as much as possible has to be factored in when making a decision to proceed. So, if there is at one point in time an indication that the FDA would indicate that V could get NCE that would be one factor in development of the drug.

That is the first I had heard that Amarin may have been told that V would be A OK for NCE down the road.

If I can interject into the discussion. I know Kiwi realizes both arms are equal in terms of the type of subjects in it but the point is can 4 gm of EPA per day so dramatically override the poor health and habits in the active arm in such a short time? Yes it will to a degree but his point is that many don't believe it will do so to the degree of 50% risk reduction.

I guess that is why the studies have to be done. We won't know for sure until the fat lady sings.

Ray, not only is your question a great question but it also brings another one to my mind.

If a 19% reduction in those inflammation markers translate to say a 40% efficacy in something like Reduce-IT my mind is wondering about how that is all impacted by the statins in the study. They too apparently reduce inflammation and so I wonder if there is a diminishing return on the additional inflammation reduction provided by V?

Of course we have Jelis that showed that even with patients on statins that EPA can still offer great benefits on top of the statin.