Replies to post #198604 on Amarin Corp Plc (AMRN)

[Romon]

Whether DHA is more effective than EPA in attenuating cardiovascular risk factors in the wider population is unclear. Our review is limited by the relatively small number of good quality RCTs available that directly compare high purity EPA to DHA. There is a need for further good quality research to independently assess the effects of EPA and DHA in larger and different study populations.

[SonamKapoor]

Thanks MRC - that's why I didn't break out bio-markers; it's just how I (admittedly a shorthand) think of it. I haven't read that study, but I respect Phil Calder and will take a look at it. I'm not proficient like Tasty or AVI at mud wrestling CTs. I'm quite the cave-girl there in fact.

What do you think of this one with an eye toward Evaporate?

Nosaka trial

I realize it's P value is .02 so I'm not sure how that tightens the numerical frame around the ARR of 11.0% specifically. But, seems good, yes?

[sharinky]

You might want to find the more recent study.

[SonamKapoor]

MRC, I quickly scanned the Calder link - Ah OK, so its another systematic review that mostly quotes Western sources. They might be missing what's been coming out of Japan for the last 5+ years.

Here's another one with an eye toward Evaporate that showed DHA/AA ratio didn't work out to reduce MACE:

Nishizaki Y 2014, Am J of Cardiology, compare EPA to DHA

[oneragman]

MRC, you predict 3 things. MO interferes with a statin. There will be an AdCom, and the patents won't hold. When you are proven wrong about MO and an AdCom in the next couple of months, do you refund 2/3 of that $32,000 to those that may have purchased it? Of course it will take a little longer, but we should take up bets on you going 0 for 3. That's where I am putting my money!

[jessellivermore]

Pyrr...et al....

This quite a paper...Scholarly..extensive and comprehensive...And well referenced..The paper does make an excellent case for DHA being more effective at reducing systemic inflammation and potentially being effective therapeutically than EPA....

Unfortunately at this time there is no R-I study that has used DHA in lieu of EPA to discredit Amarin's monumental R-I outcomes trial...So until someone does run a R-I trial using DHA...Then all the great science reported in this article doesn't mean anything...

THere are several issues brought forth in this article that fly in the face on what is generally accepted by experts on Omega-3s...One is that DHA does not interact with COX or LOX cell membrane eicosanoid receptors because it lacks the specific 3-D shape to fit the receptors...These membrane receptors are present on all body cells except Erythrocytes (red blood cells) and these receptors along with PPAR receptors in the nuclear membrane are the principal determinants of Systemic Inflammation (SI)..This paper seems to ignore this widely held observation...An observation which is consistent with the R-I results...and is the basis for the EPA/AA hypothesis...

The authors of this paper make no bold statements..And if you are proposing that DHA has a greater effect on SI than EPA you are going to need more proof than this paper provides you are going to need to post an RCT an outcomes trial that shows DHA can surpass the the R-I trial results...

":>) JL

[SonamKapoor]

Thanks JL. MRC, I'm pretty sure I recall that "about" 8x from Japan linkages. So, yes, if a person wanted to discount everything out of Japan then that could certainly be a basis for their argument construction.

The decades old roots leading up to the most recent clinical trial inquiries of the past 5 years in Japan would be the Chiba Field Study -- Hisayama Study -- JELIS. As an illustration, in 1992 Japan was already looking at EPA in terms of anti-thrombotic effects and publishing their findings in Rinsho Iyaku (J Clin Ther Med); see: Goto Y and Kumagai A.

Perhaps, you think it too pat an answer my half-Asian roots as to why I would put faith in unblinded Japanese trials? Here's why. The Japanese, albeit generally speaking, are meticulous and fastidious with detail. It's not mere pedantry, although to Americans it often comes off as such. It's more for the love of the process as an end unto itself - like the Golden Ratio unfolding before their eyes. I think of them as the Germans of Asia. Or maybe it's Germans are the Japanese of Europe. Much like Germany, if I were to pull from Jungian theory, I'd say both nations display a cultural predilection toward ISTJ tendencies. How have I seen this in everyday life? Kindergartners ride the subway by themselves safely. I haven't seen any other country where people line up straight while waiting for trains on the platform - not even Germans do this. Cochrane meta-analysis don't account for these differences in our cultural maps when they strike trials from their record. So, if a Japanese patient is given a pill with instructions they will follow it faithfully for the concomitant details to be recorded by their clinician. (Now, Americans - we are a rowdy bunch, more like ESTJs).

So, yes Calder is good and his model of lipid rafts and EPA/DHA enhancing fluidity in the lipid bilayer as well as free floating outside/inside the bi-layer. These models have been extended by Olefsky in California on functioning GPR120s and dysfunctioning R270Hs effects.

Anyway, Calder was out in Seattle last year and JL & I posted here about his bio-availability research last fall (Calder works a bit with GSK (feeds into their R&D for O-3 products) and that area of the UK is a knowledge cluster for O-3s). o3 bio-avail does it matter

So, really Calder systematic reviews + trials with GSK sponsorship is a little analogous to Japanese systematic reviews + trials Amarin has sponsored. It's the pharma business, after all right? But, I like Amarin's reviews + trials on the subject of EPA. Seeing is believing and I'll do an astronomy post soon to that end. Writing about it helps me retain fluidity on my own lipid raft of understanding.