Amarin Corp Plc (AMRN)

[rosemountbomber]

Apologies if this has already been mentioned

But I came across an interesting post on another message board that highlights that in the
IMPROVE -IT trial triglycerides as well as LDL-C were lowered in the drug combo group.

The author's point (or at least suggestion for thought) is that possibly the benefits seen in the study could be not only due to the LDL-C lowering but also/or the trig lowering, which might bode well for Vascepa in the Reduce-IT trial. Anyway here is the post:

http://www.investorvillage.com/smbd.asp?mb=2294&mn=1662&pt=msg&mid=14398093

I am pasting the post below but unfortunately the paste does not show the graphs he posted.


The million (no, billion) dollar question
This week results from IMPROVE-IT were released. The trial enrolled 18144 high risk patients and observed over 5000 events. It was able to detect a very small (“modest”) outcome benefit by the addition ezetimibe to statin therapy.

This modest benefit, as measured by a decrease in cardiac events over 7 years in a huge trial, was attributed to the LDL-C lowering effect of ezetimibe. In addition, many claim the trial “confirmed” the LDL-C hypothesis: the lower the LDL-C, the better. Hard to argue with that conclusion (but I will) considering that the control group (just statin) had incredibly low LDL-C and the ezetimide group had even lower LDL-C. In the words of the lead researcher, Dr. Cannon: “We took patients from a clinically appropriate target LDL-C to even lower. We now have solid evidence that lower is good, and even lower can be even better”.
Seems like common sense that the reduction in risk is attributed to the further reduction in LDL-C that the ezetimibe group realized. But perhaps there is more to the story.

It is generally recognized that most of the benefit of lowering LDL-C is achieved in the population of those who have high LDL-C. The CTTC meta-analysis suggests a diminishing benefit with lower baseline LDL-C. There were very few (if any) data points on the lower end of the curve below to demonstrate that there is not a point, below which, further reduction in LDL-C is beneficial. Cannon’s statement is basically saying “we provided that point”.



But there is something else interesting (and relevant to AMRN shareholders) about the IMPROVE-IT results: Not only was LDL-C lowered in the treatment arm, but trigs were lowered too.



Yet the benefit of ezetimibe is attributed (by virtually everyone) to the fact that it lowered LDL-C.

How do we know it’s not due to the lowering of trigs?

Maybe, just maybe, there is no benefit to further reducing already low LDL-C. There was no enrollment requirement for trigs, perhaps the benefit is attributable to trig lowering in the high trig population. And perhaps that modest benefit was only observed because of the very large size of the trial.

One way to shed light on this, of course, is to look at a Forrest plot for different values of baseline trigs. Was the benefit observed in the high trig sub group? We don’t know because that data has not yet been presented.

When you look at similar subgroup data (high trig) from the 3 trials the FDA used to shoot ANCHOR down (AIM-HIGH, HPS2-THRIVE and ACCORD-LIPID) you see, in each one, suggestion of greater benefit (though not SS) in high trig populations. And, while it’s risky enough trying to interpret sub-group data, it is extra questionable when the subgroup data come from failed trials (trials not meeting their primary endpoint). The FDA, in particular, does not like to do that.

But here, for IMPROVE-IT, we have a trial that did indeed hit their primary endpoint. Unfortunately they have not presented the subgroup data to see what effect reducing trigs had on the high trig subgroup. Sure would be interesting to see.

Maybe its nothing.