Replies to post #31195 on Amarin Corp Plc (AMRN)

[mrmainstreet]

JL,HD, and others, how do the JELIS results align with the recent NEJM news on TG's? Does this provide insight into possible REDUCE-IT efficacy in your opinion?

[Whalatane]

Thanks JL

A well written and informative post which I intend to study early in the am after an expresso ...

By the way ..you are very well read ...the term Huzzah in your congrtas note to BioChia

Either you love Shakespeare , have been in an English rowing crew or have spent to much time in English Pubs ...Hip Hip Hooray

Kiwi

[Whalatane]

JL

Quick comment
In the Jelis SIG group ...Is this the subgroup with HDL below 40 and TGs over 200
Most trials have suggested benefit in at least this subgroup and I believe Dr Nissens trial with Omethera requires you to be low HDL / high TG

From memory ...low HDL was not a prerequisite to be in RI ...so that may slow events.
However ..they were increasingly recruiting from Eastern Europe where as many as 40% of the males have CV events by age 50 ....so that may speed things up

Kiwi

[rafunrafun]

So what is the earliest possible date that the R-IT is terminated early for fantastic efficacy? In this best case scenario, where do you see PPS being the next day?

[Whalatane]

Hi JL

Can you post a link ( or write the heading ) for the Jelis secondary intervention group analysis.
I remember reading it but can't find it now.

I'm not sure you can say the Reduce It patients are at twice the risk as the Jelis SIG group , but would need to read the report again .
Or say we will see 355 events per year, once we hit 7,000 patients .

I just think there are two many variables to have high confidence in those estimates altho they do line up rather well with HDGators 5% event rate .

You state " The annual event rate in the statin only , which resembles the placebo group in Reduce It "group ....."
Sorry ..I don't think the Statin only Jelis SIG group resembles RI Placebo group enough to support your calculations.
RI placebo group is effectively taking as much as 4x the Statin dose as Jelis SIG group ( stronger statins at higher dose ) so they may resemble them in risk factors but not in the Statin dose they were on.

You do state that Jelis SIG group scored stat sig MACE at 4.5 yrs so if RI patients equaled out ( all factors considered ) to Jelis SIG group ...that would take us to mid 2016 .

Regarding the LDL factor ...As you have reminded us ...the true benefit from Statins may be in the lowering of inflammation ( hsCRP in the Jupiter trial ) ...not simply in the lowering of LDL. So even if we discount LDL we must acknowledge the anti inflammatory effect of stronger stains at higher dose used by patients in Reduce It

I do think the RI group is higher risk then the Jelis SIG group ,just not to the extent you calculate .
JMO
Always enjoy reading your posts ...especially the ones with the random ( and quite unusual ) quotes

Kiwi

[Whalatane]

JL

Quick follow up

On reading an old post by Biwatch #27152.

He is estimating 443 MACE events by August 6th and "about every day we should have a new event "...so that will take us to about 800 events by August 2015.

In which case I expect the DMC may wait until they hit the agreed on interim analysis # of 967 ...so at an event rate of 1 a day ...that takes us into early 2016 ...unless there is a wide enough divergence in event lines with high enough confidence to enable the DMC to advise stopping the trial for efficacy before then.

And there in lies the gamble as I don't see Amarins cash lasting much ( if at all ) into 2016

Kiwi

[jessellivermore]

One more time..

A very important point JELIS points out is the effect increasing "risk" has on outcomes studies. JELIS enrolled 18,645 patients. These patients were divided into primary or secondary interventions. Primary intervention is defined by patients not having a history of a serious CVD event. 14,981 JELIS patients fell into this group. Secondary intervention patients were those who had a history of a CVD event. 3664 JELIS patients had a positive history of a CVD event.

The reason for this division is that the risk of a patient having additional CVD events is much higher if a patient has had a previous one. In JELIS even though there 11,317 more patients in the primary group than the secondary, there were more CVD events 335 in the secondary group, than there were in the primary, only 231.

Remember in the JELIS secondary group there was a total of 355 events in 3664 patients...That was 197 events in control and 158 in the EPA group. This was stat sig for everything but mortality rates. The annual event rate for the statin only 2ndary group was only 2.3%. This is less that half the estimated event rate in the R-IT trial..(our patients are much sicker) also the JELIS secondary group was only 3664 patients which is about half the number in REDUCE-IT..JELIS ran for four and half years..We should be able to see much more in half that time..

":>) JL